This document discusses IgG food allergy testing using ELISA (Enzyme-Linked Immunosorbent Assay). It notes that while IgE-mediated food allergies are well-established, most food allergies involve non-IgE immune responses detectable by IgG testing. The document examines limitations of traditional IgE tests like skin prick tests and discusses advantages of ELISA for detecting both IgE and IgG responses. It emphasizes the importance of IgG in delayed food allergies and outlines technical and quality standards laboratories must meet to ensure ELISA provides reliable, reproducible and valid results.
Alpha-Gal Syndrome, also known as red meat allergy, is caused by IgE antibodies against the carbohydrate galactose-alpha-1,3-galactose (α-Gal) found in most mammals except primates. Tick bites transmit α-Gal to humans, causing an immune response. Reactions to red meat occur 2-6 hours after consumption due to the delayed absorption of α-Gal from glycoproteins and glycolipids. Management involves avoiding red meat, organs, and secondary exposures. The syndrome is increasingly recognized globally where ticks that transmit α-Gal are present.
This document discusses wheat allergy and related topics. It begins by classifying wheat taxonomically and describing its major protein components, many of which are allergens. It then discusses the epidemiology and clinical manifestations of wheat allergy, including immediate IgE-mediated reactions, allergic contact urticaria, baker's asthma, food-dependent exercise-induced anaphylaxis, associations with atopic dermatitis, and eosinophilic gastrointestinal disorders. Mechanisms of allergenic cross-reactivity between wheat and other cereals as well as grasses are also reviewed.
This document summarizes research on wheat allergy. It finds that wheat allergy prevalence is approximately 0.4-1% in children and 0.3-0.5% in adults. Symptoms typically present as skin reactions, gastrointestinal issues, or respiratory symptoms. Wheat allergy often resolves by ages 6-7. Key wheat allergens include alpha-amylase inhibitors, lipid transfer proteins, gliadins and glutenins. Diagnosis involves tests for wheat-specific IgE or oral food challenges. Wheat allergy is associated with increased risk of developing respiratory allergies.
The document summarizes wheat allergy, including its prevalence, major wheat proteins and allergens, cross-reactivity with other grains, and clinical manifestations. Some key points:
- Wheat allergy prevalence varies from 0.4-1% depending on age and region, and is particularly common in Japanese and Thai children.
- Major wheat allergens include omega-5-gliadin, lipid transfer proteins, glutenins, and alpha-purothionin.
- There is extensive cross-reactivity between wheat and other grains like rye and barley due to similar protein structures.
- Clinical manifestations include atopic dermatitis, anaphylaxis, baker's asthma
Omalizumab is an anti-IgE monoclonal antibody approved for treating allergic asthma, chronic urticaria, and other allergic diseases. It binds to IgE and forms complexes that are cleared, reducing free IgE levels and decreasing FcεRI expression on mast cells and basophils. For asthma, omalizumab improves symptoms and lung function and reduces exacerbations and steroid use. It may be more effective in patients with elevated type 2 biomarkers. Omalizumab also improves symptoms of chronic urticaria by decreasing mediators released in response to autoantibodies. Other anti-IgE biologics in development have distinct binding properties from omalizumab.
The document discusses vaccine hypersensitivity and provides the following information:
1. It outlines the evolution of immunization programs from the pre-vaccine era to modern times and discusses the relationship between vaccine usage and adverse events.
2. It reviews the epidemiology of immediate hypersensitivity reactions to vaccines in the US and Australia, finding reporting rates of 10 per 100,000 doses in the US and incidence of potential IgE-mediated reactions of 5.4 per 100,000 doses in Australia.
3. It examines allergic reactions to specific vaccine constituents like gelatin and egg, noting the need to consider alternative vaccines or precautions in individuals with a history of allergy to these ingredients.
Alpha-Gal Syndrome, also known as red meat allergy, is caused by IgE antibodies against the carbohydrate galactose-alpha-1,3-galactose (α-Gal) found in most mammals except primates. Tick bites transmit α-Gal to humans, causing an immune response. Reactions to red meat occur 2-6 hours after consumption due to the delayed absorption of α-Gal from glycoproteins and glycolipids. Management involves avoiding red meat, organs, and secondary exposures. The syndrome is increasingly recognized globally where ticks that transmit α-Gal are present.
This document discusses wheat allergy and related topics. It begins by classifying wheat taxonomically and describing its major protein components, many of which are allergens. It then discusses the epidemiology and clinical manifestations of wheat allergy, including immediate IgE-mediated reactions, allergic contact urticaria, baker's asthma, food-dependent exercise-induced anaphylaxis, associations with atopic dermatitis, and eosinophilic gastrointestinal disorders. Mechanisms of allergenic cross-reactivity between wheat and other cereals as well as grasses are also reviewed.
This document summarizes research on wheat allergy. It finds that wheat allergy prevalence is approximately 0.4-1% in children and 0.3-0.5% in adults. Symptoms typically present as skin reactions, gastrointestinal issues, or respiratory symptoms. Wheat allergy often resolves by ages 6-7. Key wheat allergens include alpha-amylase inhibitors, lipid transfer proteins, gliadins and glutenins. Diagnosis involves tests for wheat-specific IgE or oral food challenges. Wheat allergy is associated with increased risk of developing respiratory allergies.
The document summarizes wheat allergy, including its prevalence, major wheat proteins and allergens, cross-reactivity with other grains, and clinical manifestations. Some key points:
- Wheat allergy prevalence varies from 0.4-1% depending on age and region, and is particularly common in Japanese and Thai children.
- Major wheat allergens include omega-5-gliadin, lipid transfer proteins, glutenins, and alpha-purothionin.
- There is extensive cross-reactivity between wheat and other grains like rye and barley due to similar protein structures.
- Clinical manifestations include atopic dermatitis, anaphylaxis, baker's asthma
Omalizumab is an anti-IgE monoclonal antibody approved for treating allergic asthma, chronic urticaria, and other allergic diseases. It binds to IgE and forms complexes that are cleared, reducing free IgE levels and decreasing FcεRI expression on mast cells and basophils. For asthma, omalizumab improves symptoms and lung function and reduces exacerbations and steroid use. It may be more effective in patients with elevated type 2 biomarkers. Omalizumab also improves symptoms of chronic urticaria by decreasing mediators released in response to autoantibodies. Other anti-IgE biologics in development have distinct binding properties from omalizumab.
The document discusses vaccine hypersensitivity and provides the following information:
1. It outlines the evolution of immunization programs from the pre-vaccine era to modern times and discusses the relationship between vaccine usage and adverse events.
2. It reviews the epidemiology of immediate hypersensitivity reactions to vaccines in the US and Australia, finding reporting rates of 10 per 100,000 doses in the US and incidence of potential IgE-mediated reactions of 5.4 per 100,000 doses in Australia.
3. It examines allergic reactions to specific vaccine constituents like gelatin and egg, noting the need to consider alternative vaccines or precautions in individuals with a history of allergy to these ingredients.
Immunoglobulin therapy can be indicated for several conditions. It is clearly indicated for agammaglobulinemia due to the absence of B cells to prevent infections. For hypogammaglobulinemia with impaired antibody function, immunoglobulin therapy reduces infection rates. The appropriate immunoglobulin level to maintain an infection-free state can vary between patients. Immunoglobulin may also be used for normal immunoglobulin levels with selective antibody deficiencies if antibiotics are not controlling infections. Hypogammaglobulinemia with normal antibody responses usually does not require treatment.
This document discusses the immunologic mechanisms of anaphylaxis. It describes IgE-dependent and IgG-mediated pathways that can trigger anaphylaxis through cross-linking of antibodies on mast cells and basophils. It also discusses non-immunologic triggers like direct mast cell activation and complement activation. A variety of mediators are released that can cause signs and symptoms. The classification of reactions and potential effector cells involved are presented.
This document provides an overview of peanut allergy, including its prevalence, genetics, environmental risk factors, allergens, effects of processing, clinical manifestations, environmental exposure, diagnosis, cross-reactivity, natural history, treatment, and prevention. Some key points include:
- Peanut allergy prevalence is approximately 2% in US children and 1.8% in US adults. Rates are highest in English-speaking countries.
- Genetics play a strong role, with 64% concordance in identical twins. Several loci have been identified that increase risk.
- Major allergens include Ara h 1, Ara h 2, Ara h 3, and Ara h 6, which are resistant to heat and digestion
Red meat allergy, also known as alpha-gal allergy, is caused by IgE antibodies to the carbohydrate epitope galactose-alpha-1,3-galactose (alpha-gal) found in mammalian meats. Certain tick bites, such as from the lone star tick, are associated with the production of these IgE antibodies. Reactions to red meat following tick bites are often delayed 3-6 hours after ingestion. The discovery of the alpha-gal allergy has provided insights into regional differences in food allergies and advanced understanding of how environmental exposures can induce novel food allergies.
Oral allergy syndrome (OAS) is caused by cross-reactivity between pollen and certain raw fruits and vegetables. It occurs in up to 70% of pollen-allergic patients and involves oral itching and inflammation upon eating raw foods. Cross-reactivity is due to structural similarities between pollen and food allergens like profilin, PR-10, and lipid transfer proteins. Diagnosis involves a clinical history and skin or blood tests to specific food allergens. Treatment focuses on avoidance of raw foods and use of antihistamines for symptoms.
This document provides an overview of shellfish allergy, including:
- Classification of different types of shellfish such as crustaceans, mollusks, and others.
- Epidemiology showing shellfish allergy prevalence is around 2% and is a common cause of anaphylaxis.
- Major allergens in shellfish like tropomyosin and their heat stability and cross-reactivity.
- Clinical manifestations ranging from mild oral symptoms to anaphylaxis and factors affecting reactions.
- Diagnosis involving patient history, skin prick tests, food challenges and IgE antibody tests to confirm allergy.
Increase your Understanding of the Pathogenesis of Gluten Spectrum DisordersCell Science Systems
Recently, researchers at Harvard University, Alessio Fasano et. al., and the National Institutes of Health (laboratories of immunology and cellular and molecular biology), reported real-time microscopic observations of gluten-induced neutrophil activation.
According to authors, " To what extent neutrophil function adds to, or protects against, gluten intolerance is currently under vigorous investigation."
This presentation will shed light on this question. It will also review the Fasano study and examine the role of neutrophil function in multiple disease conditions, as well as explore how neutrophil function may also play a dual role in protecting the body from the untoward effects of dietary and environmental agents.
This document summarizes information about wheat allergy, including its prevalence, wheat proteins and allergens, clinical manifestations, diagnosis, and management. Some key points:
- Wheat allergy prevalence varies by age and region, ranging from <1% to over 3% in Europe and the US. It is less common in Asia-Pacific regions.
- Major wheat allergens include alpha-amylase inhibitors, lipid transfer proteins, gliadins like omega-5-gliadin, and glutenins. These can cause reactions from baker's asthma to food allergy.
- Clinical manifestations depend on exposure route and age. Symptoms include immediate reactions like anaphylaxis as well as
The document discusses alpha-gal syndrome, which causes delayed allergic reactions to red meat in some individuals. It may be triggered by tick bites that induce IgE antibodies against the alpha-gal oligosaccharide found in mammalian meat. Patients report generalized hives, swelling, or anaphylaxis hours after eating beef, pork or lamb. The condition is diagnosed by positive tests for alpha-gal IgE antibodies. Management involves strictly avoiding all mammalian meat and organs as well as tick bites. The cause of the delayed reactions and high antibody levels from tick bites remains unknown.
Immune tolerance is induced through central and peripheral mechanisms that eliminate or suppress self-reactive immune cells. Central tolerance occurs in the thymus and bone marrow where high-affinity self-reactive T and B cells undergo apoptosis or receptor editing. Peripheral tolerance includes anergy induction, suppression by regulatory T cells (Tregs), and inhibition by receptors like CTLA-4 and PD-1. Tregs expressing the transcription factor FoxP3 are critical for maintaining tolerance and preventing autoimmunity. Failure of these tolerance mechanisms can lead to autoimmune disease.
This document provides an overview of immunoglobulin E (IgE) and IgE receptors. It discusses the history and discovery of IgE, the structure and function of IgE, and IgE receptors such as FcεRI and CD23. It also covers the clinical significance of IgE levels in various diseases, including allergic diseases, infections, and non-atopic diseases. IgE plays an important role in type I hypersensitivity reactions and defense against parasites. The production and role of IgE is highly complex and involves interactions between immune cells, cytokines, and environmental exposures.
This document summarizes information about fish allergy. It discusses the epidemiology of fish allergy, classification of different types of fish, major fish allergens like parvalbumin and tropomyosin, diagnosis of fish allergy using methods like skin prick tests and IgE testing, cross-reactivity between fish species, and non-allergic adverse reactions to fish like scombroid poisoning and marine algae toxins. The classification section describes the different phylogenetic groups of fish including cartilaginous fish, ray-finned fish, and lobe-finned fish.
Sulfonamide allergy is common, occurring in 3-8% of the general population. It can cause minor reactions like maculopapular rashes or major life-threatening reactions like Stevens-Johnson syndrome. Risk factors include HIV infection and certain genetic factors. Diagnosis involves a clinical history and drug challenges may be used. Management involves avoiding sulfonamides that caused a reaction, though desensitization protocols have been used for HIV patients who need sulfonamide treatment.
This document discusses molecular-based allergy diagnostics and provides definitions and concepts. It outlines how molecular allergy diagnostics can increase the accuracy of allergy diagnosis by helping to resolve cross-reactivity between allergens and distinguish primary sensitizations. It also describes how molecular diagnostics can help assess the risk and type of allergic reaction, and identify specific allergens relevant for immunotherapy. A wide range of purified and recombinant food, aeroallergen, and other allergens are available to facilitate these applications.
Explore the cell's role in mediating adverse reactions 7 c09Paul Thiessen
This document discusses the role of neutrophils and macrophages in mediating various physiological and pathological processes. It summarizes several scientific studies that found:
1) Neutrophils can be recruited by substances like gliadin and mediate local inflammatory responses in tissues like the intestine.
2) Neutrophils and macrophages produce reactive molecules that can damage cells and tissues, and their activation levels correlate with conditions like infertility and acute coronary syndrome.
3) Chronic activation of the innate immune system by these cells may underlie metabolic syndrome by stimulating inflammation and hormonal changes.
4) Oxidative stress can increase blood levels of modified lipids implicated in atherosclerosis, coinciding with increased neutrophil counts.
This document summarizes a research article that studied the relationship between obesity, diabetes, and immune responses against gut bacteria. The key findings were:
1) Obese patients with diabetes had higher levels of IgG antibodies against pathogenic E. coli compared to lean controls, while IgG levels against other bacteria were unchanged.
2) Circulating tumor necrosis factor (TNF) levels were elevated in obese diabetic patients and correlated with IgG levels against E. coli.
3) Mice fed a high-fat diet developed glucose intolerance, inflammation, and higher IgG levels against pathogenic E. coli, mirroring the human findings.
The results suggest that specific gut bacteria may contribute to metabolic inflammation and diabetes associated with
This document provides an overview of latex allergy. It discusses the epidemiology and risk factors for latex allergy, including high-risk groups like healthcare workers and individuals with spina bifida. It describes the major latex allergens and clinical manifestations such as contact dermatitis, urticaria, angioedema, and anaphylaxis. The document outlines the diagnostic approach for latex allergy including taking a clinical history, skin prick testing, serum specific IgE testing, and challenge tests if needed. It also discusses management of latex allergy through avoidance of latex products and emergency treatment of reactions.
This document summarizes the history and evolution of allergy testing from 1880 to present day. It discusses early methods like provocation testing and the characterization of IgE in the 1960s-1970s. Modern developments introduced recombinant allergens in 1995, allergen microarrays in 2001, and now over 103 molecular allergens can be tested. The document also presents and analyzes three case studies involving pollen, latex, and food allergies. It emphasizes that both traditional testing with extracts and newer molecular testing are still needed due to the complexity of allergies. CRD and molecular allergology are active areas of research that young allergists should learn alongside traditional diagnostics.
- Nut allergy is commonly caused by peanuts and tree nuts and can cause anaphylaxis. Peanut allergy prevalence is 0.5-2.5% in children in the UK and tree nut allergy prevalence is 0.2-2.2%.
- Diagnosis involves taking a history, skin prick tests, nut-specific IgE levels, and oral food challenges. Skin prick tests ≥3mm or nut-specific IgE levels ≥15kU/L suggest allergy.
- Cross-reactivity between peanuts and tree nuts is common, so testing for multiple nuts is often recommended for those allergic to one type of nut. Component resolved testing for Ara h 2
Alergias mediadas por anticuperpos ig e versus alergias mediadas por iggMEDIAGNOSTIC
IgG-mediated food sensitivity reactions are delayed, taking hours or days to appear after ingesting the offending food. Unlike immediate IgE-mediated food allergies, IgG sensitivities are difficult to detect without specialized testing and can involve multiple foods. Symptoms of IgG food sensitivity can affect any tissue or organ and include conditions like irritable bowel syndrome, asthma, and behavioral issues in children. Testing for IgG antibodies to specific foods can help identify sensitivities and guide elimination diets to improve conditions like rheumatoid arthritis and autism.
The five classes of antibodies are IgG, IgM, IgA, IgD, and IgE. IgG makes up around 80% of antibodies in serum and protects against circulating bacteria and viruses. IgM is involved in the primary response and is the first antibody to appear after infection. IgA is most common in mucous membranes and body secretions where it helps prevent pathogen attachment. IgD's function is unknown, while IgE binds to mast cells and basophils to trigger allergic reactions. Each class has distinct properties, locations, functions, and roles in the immune response.
Immunoglobulin therapy can be indicated for several conditions. It is clearly indicated for agammaglobulinemia due to the absence of B cells to prevent infections. For hypogammaglobulinemia with impaired antibody function, immunoglobulin therapy reduces infection rates. The appropriate immunoglobulin level to maintain an infection-free state can vary between patients. Immunoglobulin may also be used for normal immunoglobulin levels with selective antibody deficiencies if antibiotics are not controlling infections. Hypogammaglobulinemia with normal antibody responses usually does not require treatment.
This document discusses the immunologic mechanisms of anaphylaxis. It describes IgE-dependent and IgG-mediated pathways that can trigger anaphylaxis through cross-linking of antibodies on mast cells and basophils. It also discusses non-immunologic triggers like direct mast cell activation and complement activation. A variety of mediators are released that can cause signs and symptoms. The classification of reactions and potential effector cells involved are presented.
This document provides an overview of peanut allergy, including its prevalence, genetics, environmental risk factors, allergens, effects of processing, clinical manifestations, environmental exposure, diagnosis, cross-reactivity, natural history, treatment, and prevention. Some key points include:
- Peanut allergy prevalence is approximately 2% in US children and 1.8% in US adults. Rates are highest in English-speaking countries.
- Genetics play a strong role, with 64% concordance in identical twins. Several loci have been identified that increase risk.
- Major allergens include Ara h 1, Ara h 2, Ara h 3, and Ara h 6, which are resistant to heat and digestion
Red meat allergy, also known as alpha-gal allergy, is caused by IgE antibodies to the carbohydrate epitope galactose-alpha-1,3-galactose (alpha-gal) found in mammalian meats. Certain tick bites, such as from the lone star tick, are associated with the production of these IgE antibodies. Reactions to red meat following tick bites are often delayed 3-6 hours after ingestion. The discovery of the alpha-gal allergy has provided insights into regional differences in food allergies and advanced understanding of how environmental exposures can induce novel food allergies.
Oral allergy syndrome (OAS) is caused by cross-reactivity between pollen and certain raw fruits and vegetables. It occurs in up to 70% of pollen-allergic patients and involves oral itching and inflammation upon eating raw foods. Cross-reactivity is due to structural similarities between pollen and food allergens like profilin, PR-10, and lipid transfer proteins. Diagnosis involves a clinical history and skin or blood tests to specific food allergens. Treatment focuses on avoidance of raw foods and use of antihistamines for symptoms.
This document provides an overview of shellfish allergy, including:
- Classification of different types of shellfish such as crustaceans, mollusks, and others.
- Epidemiology showing shellfish allergy prevalence is around 2% and is a common cause of anaphylaxis.
- Major allergens in shellfish like tropomyosin and their heat stability and cross-reactivity.
- Clinical manifestations ranging from mild oral symptoms to anaphylaxis and factors affecting reactions.
- Diagnosis involving patient history, skin prick tests, food challenges and IgE antibody tests to confirm allergy.
Increase your Understanding of the Pathogenesis of Gluten Spectrum DisordersCell Science Systems
Recently, researchers at Harvard University, Alessio Fasano et. al., and the National Institutes of Health (laboratories of immunology and cellular and molecular biology), reported real-time microscopic observations of gluten-induced neutrophil activation.
According to authors, " To what extent neutrophil function adds to, or protects against, gluten intolerance is currently under vigorous investigation."
This presentation will shed light on this question. It will also review the Fasano study and examine the role of neutrophil function in multiple disease conditions, as well as explore how neutrophil function may also play a dual role in protecting the body from the untoward effects of dietary and environmental agents.
This document summarizes information about wheat allergy, including its prevalence, wheat proteins and allergens, clinical manifestations, diagnosis, and management. Some key points:
- Wheat allergy prevalence varies by age and region, ranging from <1% to over 3% in Europe and the US. It is less common in Asia-Pacific regions.
- Major wheat allergens include alpha-amylase inhibitors, lipid transfer proteins, gliadins like omega-5-gliadin, and glutenins. These can cause reactions from baker's asthma to food allergy.
- Clinical manifestations depend on exposure route and age. Symptoms include immediate reactions like anaphylaxis as well as
The document discusses alpha-gal syndrome, which causes delayed allergic reactions to red meat in some individuals. It may be triggered by tick bites that induce IgE antibodies against the alpha-gal oligosaccharide found in mammalian meat. Patients report generalized hives, swelling, or anaphylaxis hours after eating beef, pork or lamb. The condition is diagnosed by positive tests for alpha-gal IgE antibodies. Management involves strictly avoiding all mammalian meat and organs as well as tick bites. The cause of the delayed reactions and high antibody levels from tick bites remains unknown.
Immune tolerance is induced through central and peripheral mechanisms that eliminate or suppress self-reactive immune cells. Central tolerance occurs in the thymus and bone marrow where high-affinity self-reactive T and B cells undergo apoptosis or receptor editing. Peripheral tolerance includes anergy induction, suppression by regulatory T cells (Tregs), and inhibition by receptors like CTLA-4 and PD-1. Tregs expressing the transcription factor FoxP3 are critical for maintaining tolerance and preventing autoimmunity. Failure of these tolerance mechanisms can lead to autoimmune disease.
This document provides an overview of immunoglobulin E (IgE) and IgE receptors. It discusses the history and discovery of IgE, the structure and function of IgE, and IgE receptors such as FcεRI and CD23. It also covers the clinical significance of IgE levels in various diseases, including allergic diseases, infections, and non-atopic diseases. IgE plays an important role in type I hypersensitivity reactions and defense against parasites. The production and role of IgE is highly complex and involves interactions between immune cells, cytokines, and environmental exposures.
This document summarizes information about fish allergy. It discusses the epidemiology of fish allergy, classification of different types of fish, major fish allergens like parvalbumin and tropomyosin, diagnosis of fish allergy using methods like skin prick tests and IgE testing, cross-reactivity between fish species, and non-allergic adverse reactions to fish like scombroid poisoning and marine algae toxins. The classification section describes the different phylogenetic groups of fish including cartilaginous fish, ray-finned fish, and lobe-finned fish.
Sulfonamide allergy is common, occurring in 3-8% of the general population. It can cause minor reactions like maculopapular rashes or major life-threatening reactions like Stevens-Johnson syndrome. Risk factors include HIV infection and certain genetic factors. Diagnosis involves a clinical history and drug challenges may be used. Management involves avoiding sulfonamides that caused a reaction, though desensitization protocols have been used for HIV patients who need sulfonamide treatment.
This document discusses molecular-based allergy diagnostics and provides definitions and concepts. It outlines how molecular allergy diagnostics can increase the accuracy of allergy diagnosis by helping to resolve cross-reactivity between allergens and distinguish primary sensitizations. It also describes how molecular diagnostics can help assess the risk and type of allergic reaction, and identify specific allergens relevant for immunotherapy. A wide range of purified and recombinant food, aeroallergen, and other allergens are available to facilitate these applications.
Explore the cell's role in mediating adverse reactions 7 c09Paul Thiessen
This document discusses the role of neutrophils and macrophages in mediating various physiological and pathological processes. It summarizes several scientific studies that found:
1) Neutrophils can be recruited by substances like gliadin and mediate local inflammatory responses in tissues like the intestine.
2) Neutrophils and macrophages produce reactive molecules that can damage cells and tissues, and their activation levels correlate with conditions like infertility and acute coronary syndrome.
3) Chronic activation of the innate immune system by these cells may underlie metabolic syndrome by stimulating inflammation and hormonal changes.
4) Oxidative stress can increase blood levels of modified lipids implicated in atherosclerosis, coinciding with increased neutrophil counts.
This document summarizes a research article that studied the relationship between obesity, diabetes, and immune responses against gut bacteria. The key findings were:
1) Obese patients with diabetes had higher levels of IgG antibodies against pathogenic E. coli compared to lean controls, while IgG levels against other bacteria were unchanged.
2) Circulating tumor necrosis factor (TNF) levels were elevated in obese diabetic patients and correlated with IgG levels against E. coli.
3) Mice fed a high-fat diet developed glucose intolerance, inflammation, and higher IgG levels against pathogenic E. coli, mirroring the human findings.
The results suggest that specific gut bacteria may contribute to metabolic inflammation and diabetes associated with
This document provides an overview of latex allergy. It discusses the epidemiology and risk factors for latex allergy, including high-risk groups like healthcare workers and individuals with spina bifida. It describes the major latex allergens and clinical manifestations such as contact dermatitis, urticaria, angioedema, and anaphylaxis. The document outlines the diagnostic approach for latex allergy including taking a clinical history, skin prick testing, serum specific IgE testing, and challenge tests if needed. It also discusses management of latex allergy through avoidance of latex products and emergency treatment of reactions.
This document summarizes the history and evolution of allergy testing from 1880 to present day. It discusses early methods like provocation testing and the characterization of IgE in the 1960s-1970s. Modern developments introduced recombinant allergens in 1995, allergen microarrays in 2001, and now over 103 molecular allergens can be tested. The document also presents and analyzes three case studies involving pollen, latex, and food allergies. It emphasizes that both traditional testing with extracts and newer molecular testing are still needed due to the complexity of allergies. CRD and molecular allergology are active areas of research that young allergists should learn alongside traditional diagnostics.
- Nut allergy is commonly caused by peanuts and tree nuts and can cause anaphylaxis. Peanut allergy prevalence is 0.5-2.5% in children in the UK and tree nut allergy prevalence is 0.2-2.2%.
- Diagnosis involves taking a history, skin prick tests, nut-specific IgE levels, and oral food challenges. Skin prick tests ≥3mm or nut-specific IgE levels ≥15kU/L suggest allergy.
- Cross-reactivity between peanuts and tree nuts is common, so testing for multiple nuts is often recommended for those allergic to one type of nut. Component resolved testing for Ara h 2
Alergias mediadas por anticuperpos ig e versus alergias mediadas por iggMEDIAGNOSTIC
IgG-mediated food sensitivity reactions are delayed, taking hours or days to appear after ingesting the offending food. Unlike immediate IgE-mediated food allergies, IgG sensitivities are difficult to detect without specialized testing and can involve multiple foods. Symptoms of IgG food sensitivity can affect any tissue or organ and include conditions like irritable bowel syndrome, asthma, and behavioral issues in children. Testing for IgG antibodies to specific foods can help identify sensitivities and guide elimination diets to improve conditions like rheumatoid arthritis and autism.
The five classes of antibodies are IgG, IgM, IgA, IgD, and IgE. IgG makes up around 80% of antibodies in serum and protects against circulating bacteria and viruses. IgM is involved in the primary response and is the first antibody to appear after infection. IgA is most common in mucous membranes and body secretions where it helps prevent pathogen attachment. IgD's function is unknown, while IgE binds to mast cells and basophils to trigger allergic reactions. Each class has distinct properties, locations, functions, and roles in the immune response.
This document discusses types I and II hypersensitivity reactions. It begins by defining hypersensitivity reactions as exaggerated or inappropriate immune responses against antigens or allergens. It then discusses the classification system proposed by Gell and Coombs which divides hypersensitivity into four types: IgE-mediated (type I), antibody-mediated/IgG-mediated cytotoxic (type II), immune complex-mediated (type III), and cell-mediated or delayed-type hypersensitivity (type IV). The document focuses on types I and II, providing details on the mechanisms, examples, and treatments of IgE-mediated and antibody-mediated cytotoxic hypersensitivity reactions.
allergic diseases, atopic,bronchial asthma Hash Shah
This document discusses allergic diseases and their diagnosis. It notes that the incidence of allergic conditions like asthma and allergic rhinitis are rising. Atopy, the genetic predisposition to develop IgE antibodies, involves complex genetic and environmental factors. Allergic disorders are caused by type I hypersensitivity reactions and IgE-mediated immune responses. Diagnosis involves taking a thorough history, and may include nonspecific tests like CBC and IgE levels or more specific tests like skin prick tests and allergen-specific IgE blood tests to identify triggers.
Immunoglobulin Test: Impact of High Immunoglobulin Levels (IgA) | The Lifesci...The Lifesciences Magazine
An immunoglobulin test stands as a pivotal diagnostic procedure, delving into the intricate realms of the immune system by measuring the levels of immunoglobulins in the bloodstream.
This document summarizes the five classes of human immunoglobulins (Igs): IgG, IgA, IgM, IgD, and IgE. It describes the key properties and functions of each Ig class, including their structure, abundance in serum, role in immune responses, and ability to activate complement or cross the placenta. IgG is the most abundant Ig and can cross the placenta to provide immunity to newborns. IgA exists as a monomer in serum but a dimer linked by a joining peptide in secretions to protect mucosal surfaces. IgM is the first antibody produced during a primary immune response.
This document discusses food allergens and food allergy. It defines a food allergen as a normally harmless food protein that causes an allergic reaction in susceptible individuals. The most common food allergens are listed as milk, egg, peanut, wheat, fish, soy, tree nuts. It also discusses the symptoms of food allergies, which can range from mild to severe and life-threatening. While promising research is underway, food allergies currently cannot be cured. The document provides information on diagnosing and managing food allergies.
This document discusses a case of a man diagnosed with IgA and IgG subclass deficiencies. The patient had a history of chronic sinusitis and pneumonia. Immunological tests showed reduced levels of IgA and various IgG subclasses. IgA and IgG subclass deficiencies can cause increased susceptibility to infection. Treatment may include intravenous immunoglobulin, antibiotics, vaccines, and surgery for issues like chronic sinusitis. These deficiencies are inherited and affect about 1 in 700 Caucasians, increasing risks for recurrent respiratory infections and allergic/autoimmune disorders.
La alergia a limenticia en el síndrome de colon irritable. nuevos hechos y vi...MEDIAGNOSTIC
This document discusses the notion of food allergy in irritable bowel syndrome (IBS). Recent evidence suggests that elimination diets based on foods against which patients have raised IgG antibodies can significantly reduce IBS symptom severity. The findings encourage further study of the mechanisms behind IgG production against dietary antigens and their potential role in IBS. A healthy gut microbiota is an important part of gut barrier function, and the role of the gut microbiota in IBS pathogenesis deserves closer examination. Modulating the gut microbiota composition or activity could provide novel therapeutic approaches for IBS beyond elimination diets.
Immunoglobulins, also known as antibodies, are glycoproteins produced by plasma cells that recognize and bind to specific antigens. There are five main classes of immunoglobulins - IgG, IgA, IgM, IgD, and IgE - which differ in their structure and function. IgG is the most abundant antibody found in serum and body tissues, while IgA is predominantly found in secretions such as breast milk, tears, and saliva where it provides immune protection of mucosal surfaces. IgM is the first antibody to respond to new antigens and plays a key role in activating the complement system.
This document discusses selective immunoglobulin A (IgA) deficiency. It begins by defining immunoglobulins, antibodies, and the process of class switching that allows antibodies to change class. It then discusses affinity maturation, where antibodies increase in affinity for antigens over time. Selective IgA deficiency is defined as having low or absent levels of the IgA antibody. Causes may include genetics or unknown factors. Risk is higher in Caucasians. Most people are asymptomatic, but some experience recurrent infections. Diagnosis involves blood tests showing low IgA levels. Treatment focuses on infection management and preventative vaccines. IVIG can treat associated deficiencies.
The document discusses allergies and anaphylaxis. It defines allergies as hypersensitive reactions to allergens that come into contact with the skin, nose, eyes, or respiratory/gastrointestinal tracts. Anaphylaxis is a severe allergic reaction that can be life-threatening. The immune system normally produces antibodies to defend against harmful substances, but in allergies it overreacts to harmless substances. Allergic reactions are classified based on their mechanisms and time courses. Type 1 reactions are immediate and IgE-mediated, like anaphylaxis. Skin prick and serum IgE tests can help identify allergens and prevent severe allergic reactions. Proper medical history is important
1. Dendritic cell-bound IgE functions to restrain allergic inflammation at mucosal sites. In humans, but not mice, dendritic cells express the IgE receptor FcεRI which is constitutively occupied with IgE.
2. The study found that humanized mice expressing FcεRI on dendritic cells like humans carry IgE but do not develop spontaneous allergies. Antigen-specific IgE/FcεRI cross-linking on dendritic cells fails to induce maturation or inflammatory mediator production.
3. Conferring FcεRI expression to dendritic cells decreases the severity of food allergy and asthma models, suggesting dendritic cell-intrinsic Ig
The usage of immunological reactions in diagnostics of infectious diseases. Eneutron
This document summarizes key concepts regarding immunological reactions used for diagnosing infectious diseases. It defines antigens and antibodies, describing their structures, properties, and functions. Antigens are non-self substances that stimulate antibody production, and have properties like foreignness, antigenicity, and specificity. Antibodies are immunoglobulins consisting of light and heavy chains that bind to antigens. The document outlines the five major immunoglobulin classes - IgG, IgA, IgM, IgD, and IgE - and their roles in the immune response. It also describes common serological diagnostic tests like agglutination and indirect hemagglutination that detect antibodies bound to antigens.
Basic immunology- Dr.Pankti Shah (PART I MDS)PanktiShah12
This document provides an overview of immunology and the immune system as it relates to dental bacterial plaque and periodontitis. It defines key terms like immunity, antigens, antibodies, and the antigen-antibody reaction. It describes the different types of immunity and components of the immune system including the complement system. It discusses the inflammatory response in the periodontium and potential for periodontal vaccines. It also covers the immunology of dental bacterial plaque and the roles of antibodies, complement activation, chemotaxis, phagocytosis, and T and B lymphocytes in the immune response to caries, gingivitis and periodontitis.
This document summarizes an article on antibiotic allergies. It discusses how antibiotic allergies are commonly documented but often unknown or not remembered by patients. Inaccurate antibiotic allergy labels can lead to increased use of broad-spectrum antibiotics and antibiotic resistance. Most patients labeled as penicillin allergic are not actually allergic when appropriately tested. The review provides an update on antibiotic allergy epidemiology, classification, mechanisms, diagnosis and management, with a focus on addressing unverified penicillin allergy labels as a threat to public health.
Antigen ,Antibody and Ag-Ab reactions ppt by DR.C.P.PRINCEDR.PRINCE C P
An immunogen refers to a molecule that is capable of eliciting an immune response, whereas an antigen refers to a molecule that is capable of binding to the product of that immune response (Ab).
So, an immunogen is necessarily an antigen, but an antigen may not necessarily be an immunogen
The terms immunogen and antigen are often used interchangeably but the later is more common.
Antibodies are Globulin Protein (Immunoglobulin) that are synthesized in the Serum and Tissue fluids.
It reacts specifically with the antigen that stimulated their production.
There are two types serum proteins: albumin and globulin
There are Three types of globulins .
1. Alpha globulin
2. Beta globulin
3. Gamma globulin (Antibodies)
Gamma globulins are responsible for immunity. So they are called as Immunoglobulin (Ig)
The binding of an antibody with an antigen of the type that stimulated the formation of antibody that results in the following reaction
Agglutination
Precipitation
Complement fixation
Phagocytosis
Neutralization of an exotoxin
Opsonization
Tissue fixation
Chemotaxis
Activation of mast cells and basophils
PPT prepared by:
DR.PRINCE C P
Associate Professor , Department of Microbiology,
Mother Theresa Post Graduate & Research Institute of Health Sciences (Government of Puducherry Institution)
This document discusses humoral immunity and antibodies. It describes how antibodies are produced by B cells and plasma cells in response to antigens. The primary role of antibodies is protection against reinfection by binding to pathogens and marking them for destruction or neutralization. The document provides details on antibody structure, classes, properties, functions, and role in immune responses.
Similar to Relevancia clínica de las pruebas tipo eliza para determinación de intolerancias alimenticias. (20)
Restricción de dieta en migraña, basada en la medición de anticuperpos ig g.MEDIAGNOSTIC
This randomized, double-blind, cross-over clinical trial investigated the effects of a diet restricted based on IgG antibodies against food antigens in 30 migraine patients. Patients underwent a 6-week baseline period, then were randomly assigned to a 6-week elimination diet excluding foods with raised IgG or a provocation diet including those foods, followed by the opposite diet. Compared to baseline and the provocation diet, the elimination diet significantly reduced the number of headache days and migraine attacks. However, attack severity and duration did not change. Order of the diets did not affect outcomes. This study provides preliminary evidence that an IgG-based elimination diet can effectively reduce migraine frequency.
Reporte de la intolerancia a los alimentos y síntomas respiratorios en adulto...MEDIAGNOSTIC
This study assessed reported food intolerance and associated respiratory symptoms in young adults in Melbourne, Australia using data from the European Community Respiratory Health Survey (ECRHS) questionnaire. Seventeen percent of respondents reported food intolerance or allergy, with a wide variety of foods cited as causes. Those reporting respiratory symptoms after food ingestion were more likely to be atopic, have used inhaled medications recently, weigh more, and have less exposure to secondhand smoke. However, current asthma was not associated with reported food intolerance. The study highlights the need for improved dietary assessment methods in investigating relationships between diet and health.
Reporte de especificidad y sensibildad de la prueba de intolerancias alimenti...MEDIAGNOSTIC
The document evaluates the performance of the Food Detective assay. It finds:
1) The limit of detection for human IgG is 1.6μg/ml.
2) The assay detects IgG antibodies to all 59 foods on the reaction tray when present at levels that test positive on a reference ELISA.
3) Absorption studies demonstrate the specificity of food antibody binding for most foods. Cross-reactivity is seen for some foods from the same plant family.
4) The assay shows highly reproducible results between different lots and plates.
5) Common interfering substances like triglycerides, hemoglobin and bilirubin do not affect the assay results.
Relación de las intolerancias alimenticias en las enfermedades crónicas.MEDIAGNOSTIC
This document discusses hidden or masked food allergies and their role in chronic disease. It notes that while controversial, evidence suggests identification and avoidance of allergenic foods through elimination diets can relieve many common medical problems. Key points:
- An estimated 60% of the population may suffer from undetected food allergies.
- Elimination diets can "unmask" hidden food allergies, allowing patients to identify symptom-causing foods through reintroduction challenges.
- Studies show elimination diets providing significant relief for many conditions like migraines, arthritis, and irritable bowel syndrome. Common allergenic foods include dairy, eggs, wheat, and chocolate.
Reacción cruzada entre los anticuerpos de los alimentos y la artritis reumatoideMEDIAGNOSTIC
This study investigated food antibodies in the serum and jejunal perfusion fluid of 14 rheumatoid arthritis (RA) patients and 20 healthy controls. The study found:
1) RA patients had significantly increased levels of IgM antibodies against various food antigens in their intestinal fluid, including cow's milk proteins, cereals, egg, fish and pork.
2) Intestinal IgA and IgG antibody activities against foods were also increased in RA patients compared to controls, though IgA increases were less consistent.
3) Treatment with sulfasalazine for 16 weeks normalized initially raised intestinal food antibody levels in 3 out of 5 RA patients tested, though clinical improvement was better reflected by reduced erythrocyte sediment
Auditoría prospectiva de la intolerancia a los alimentos entre los pacientes ...MEDIAGNOSTIC
This study prospectively audited 61 migraine patients in primary care to investigate potential food intolerances and the effects of an elimination diet. Blood samples were tested for IgG antibodies to foods and around 90% of patients changed their diet based on results. At 1-2 months, 30-40% reported considerable benefit and over 60% reported migraine return when reintroducing foods. The study demonstrated potential associations between food intolerances mediated by IgG and migraine, and that dietary changes may effectively treat migraine for some patients. Further clinical studies are warranted.
Alergia a los almentos mediadas por anticuerpos ig g asociadas con la migraña...MEDIAGNOSTIC
This document discusses a study investigating the presence of IgG antibodies to foods in patients with migraine refractory to traditional treatment. The study found:
1) Statistical significant differences in the number of positive IgG food allergens between patients with migraine (56 patients) and a control group without migraine.
2) Elimination diets successfully controlled migraines in patients, without the need for medications.
3) According to the results, serum IgG antibodies to common foods should be investigated in patients with migraine.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of the physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar lead (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
6. Describe the flow of current around the heart during the cardiac cycle
7. Discuss the placement and polarity of the leads of electrocardiograph
8. Describe the normal electrocardiograms recorded from the limb leads and explain the physiological basis of the different records that are obtained
9. Define mean electrical vector (axis) of the heart and give the normal range
10. Define the mean QRS vector
11. Describe the axes of leads (hexagonal reference system)
12. Comprehend the vectorial analysis of the normal ECG
13. Determine the mean electrical axis of the ventricular QRS and appreciate the mean axis deviation
14. Explain the concepts of current of injury, J point, and their significance
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. Chapter 3, Cardiology Explained, https://www.ncbi.nlm.nih.gov/books/NBK2214/
7. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
Promoting Wellbeing - Applied Social Psychology - Psychology SuperNotesPsychoTech Services
A proprietary approach developed by bringing together the best of learning theories from Psychology, design principles from the world of visualization, and pedagogical methods from over a decade of training experience, that enables you to: Learn better, faster!
Here is the updated list of Top Best Ayurvedic medicine for Gas and Indigestion and those are Gas-O-Go Syp for Dyspepsia | Lavizyme Syrup for Acidity | Yumzyme Hepatoprotective Capsules etc
Rasamanikya is a excellent preparation in the field of Rasashastra, it is used in various Kushtha Roga, Shwasa, Vicharchika, Bhagandara, Vatarakta, and Phiranga Roga. In this article Preparation& Comparative analytical profile for both Formulationon i.e Rasamanikya prepared by Kushmanda swarasa & Churnodhaka Shodita Haratala. The study aims to provide insights into the comparative efficacy and analytical aspects of these formulations for enhanced therapeutic outcomes.
Cell Therapy Expansion and Challenges in Autoimmune DiseaseHealth Advances
There is increasing confidence that cell therapies will soon play a role in the treatment of autoimmune disorders, but the extent of this impact remains to be seen. Early readouts on autologous CAR-Ts in lupus are encouraging, but manufacturing and cost limitations are likely to restrict access to highly refractory patients. Allogeneic CAR-Ts have the potential to broaden access to earlier lines of treatment due to their inherent cost benefits, however they will need to demonstrate comparable or improved efficacy to established modalities.
In addition to infrastructure and capacity constraints, CAR-Ts face a very different risk-benefit dynamic in autoimmune compared to oncology, highlighting the need for tolerable therapies with low adverse event risk. CAR-NK and Treg-based therapies are also being developed in certain autoimmune disorders and may demonstrate favorable safety profiles. Several novel non-cell therapies such as bispecific antibodies, nanobodies, and RNAi drugs, may also offer future alternative competitive solutions with variable value propositions.
Widespread adoption of cell therapies will not only require strong efficacy and safety data, but also adapted pricing and access strategies. At oncology-based price points, CAR-Ts are unlikely to achieve broad market access in autoimmune disorders, with eligible patient populations that are potentially orders of magnitude greater than the number of currently addressable cancer patients. Developers have made strides towards reducing cell therapy COGS while improving manufacturing efficiency, but payors will inevitably restrict access until more sustainable pricing is achieved.
Despite these headwinds, industry leaders and investors remain confident that cell therapies are poised to address significant unmet need in patients suffering from autoimmune disorders. However, the extent of this impact on the treatment landscape remains to be seen, as the industry rapidly approaches an inflection point.
Post-Menstrual Smell- When to Suspect Vaginitis.pptx
Relevancia clínica de las pruebas tipo eliza para determinación de intolerancias alimenticias.
1. The clinical relevance of IgG food allergy testing through
ELISA (Enzyme-Linked Immunosorbent Assay).
From: Townsend Letter for Doctors and Patients | Date: 1/1/2004 | Author: Suen, Raymond M.;Gordon,
Shalima
Allergic reactions to foods may be classified as either IgE-mediated or nonIgE-mediated--the
role of the former in food allergy being well-established. However, interestingly enough, the
majority of food allergies are associated with specific nonIgE-mediated immune sensitivities.
As such, appropriate tests must be utilized to identify possible causes, including food-
antigen specific IgG antibodies. There are many testing methods available for the detection
of food allergies including the skin prick test and RAST, or radioallergosorbent test.
Unfortunately, both of these methods only look for allergen-specific IgE antibodies from the
patient's serum. This poses considerable limitations in the clinical assessment of the
chronically unwell patient.
The Skin Prick Test--Pitfalls
With regards to IgE testing, the ELISA method offers an excellent confirmatory test for IgE-
mediated food allergies when skin prick testing is equivocal or negative, as it is not unusual
for a patient to be skin prick test negative and ELISA positive. Generally, the assumption in
such a case is that the extracts used for IgE skin prick testing were defective, unstable or
non-standardized. Conversely, a false positive skin test may be due to nonspecific
enhancement of the hypersensitive reaction through an axon reflex of a neighboring strong
wheal-and-flare reaction. In addition, skin prick testing does pose a health risk to the patient,
as eluates of protein extracts are pierced through the skin. Anaphylaxis is a possibility and
resuscitation equipment must be on hand. Furthermore, the results of skin prick testing do
not exhibit a strong correlation to food allergy symptoms. ELISA is reported to be more
sensitive than skin prick testing in the identification of IgE-mediated food allergies, and as
most food allergies are nonIgE-mediated, skin prick testing is rather obsolete. (1-5)
The principle behind the skin prick testing method is simple. Sensitized tissue mast cells
display IgE antibodies on their cell membranes, which through provocation by a recognized
food antigen will promote the release of histamine and other inflammatory mediators from
these immune cells. The result is a wheal-and-flare reaction marked by redness and
2. swelling. However, identification of such mast cell dependent reactions for the detection of
food allergies does have its pitfalls in addition to those mentioned. First, diseases such as
eczema may attenuate the skin response. Second, there is decreased reactivity of the skin
in infants and elderly patients making this testing method inappropriate for these
populations. In addition, mast cells from different sites of the body (skin, lungs, and
gastrointestinal tract) exhibit marked heterogeneity with respect to their functional properties.
(6) This is of fundamental importance from a clinical perspective since one cannot simply
extrapolate the results from a skin prick test and assume a direct correlation to that which is
occurring in the gut. Furthermore, skin prick testing does not assess for delayed-onset food
allergies mediated through IgG antibodies. IgG concentrations increase from repeated
exposure to food antigens. (7) IgG-mediated food reactions occur hours to days after
exposure to the incriminating foods, and unlike that of IgE, IgG related symptoms are
cumulative in nature.
Since the discovery of IgE in 1967, conventional medical practice has focused chiefly on
IgE-mediated allergies as identified primarily through skin prick testing. As our understanding
of the disease model progresses with physiological mechanisms finding root in regulation of
oral tolerance, the clinical importance of IgG antibodies is rapidly following suit as a key
player in the allergic model of disease and chronic pathology. (8)
The IgG Immunoglobulin Class
The IgG immunoglobulin class has an exceptionally long half-life in circulation and makes up
about 75% of the total serum immunoglobulin pool. This class is comprised of four known
subtypes; IgG1, IgG2, IgG3, and IgG4. IgG1 constitutes about 68% of total IgG; IGg2, 20%;
IgG3, 8%; and IgG4, 4%. IgG1 through IgG3 are capable of binding complement and
initiating complement-mediated tissue injury, whereas IgG4 is not. (9) However, it is argued
that altered IgG4 through immune complex formation may act as an autoantigen. Since IgG
levels increase with exposure, these complexes may reach appreciable levels over time.
Autoantibodies such as those of the IgM class, formed to these altered IgG4 autoantigens,
may cross-link cell-bound IgG4 and activate complement. (10) Such a mechanism has been
reported responsible for the exacerbation of symptoms in atopic eczema patients where
high-molecular-weight (i.e. 21S or more) immune complexes have been identified. (11) An
autoimmune process such as this clearly deserves considerable attention to its clinical
implications in chronic allergic disease.
3. Interesting among the IgG class of antibodies are the IgG receptors, Fc[gamma]R. Since IgG
represents the dominant antibody class in plasma, receptors for IgG have been intensively
studied over the years. (12) These receptors are found on a wide variety of immune cells
and are said to serve as a bridge between the cellular and humoral parts of the immune
system. Effector functions that can be triggered by Fc[gamma]R include; antibody-
dependent cellular cytotoxicity (ADCC), antigen presentation, cytokine release,
phagocytosis, degranulation, and regulation of antibody production. (13) With a constant
stream of IgG antibodies in circulation due to chronic challenge, inappropriate regulation of
Fc[gamma]R-mediated responses, or inefficient Fc[gamma]R function may lead to a
hyperresponsive state with greatly magnified effector responses that may subsequently
promote inflammatory disease and increase susceptibility to autoimmunity. (14-17)
The Gut Immune System
It is well known that a significant portion of ingested proteins from food reach the gut-
associated lymphoid tissues (GALT), in an immunologically intact form capable of stimulating
immune responses in the susceptible individual. This susceptibility rests in the competency
of the immunoregulatory mechanisms of the GALT that normally prevent the induction of a
hypersensitive response to otherwise innocuous food challenges. It is undesirable to be
intolerant to the foods we eat. Mobilization of the GALT against food antigens defines loss of
oral tolerance to foods, and may provoke injurious local and systemic immune responses.
The gut mucosal response, particularly that involving an antibody response, is highly
dependent on T cell help. (18) T helper pattern induced clonal expansion may proceed
through a cell-mediated (Th1) response, humoral (Th2) response, or immune tolerance
(Th3). (19) It is important to note that T cells of the mucosal lymphoid tissue are heavily
biased toward a Th2 response. This accounts for the predominance of the protective IgA
isotype in mucosal effector tissues. However, the phenotypic polarization of immunoglobulin
producing B cells favoring IgA is heavily influenced by the cytokine profile present in the
mucosal milieu. Interleukin-4 (IL-4) for example, promotes isotype switching to both IgG1
subclass and IgE (20) whereas, the cytokine transforming growth factor beta (TGF-[beta])
favors B cell class switching from IgG and IgE to IgA, thereby suppressing any potential for a
Th1 or Th2 inflammatory response to dietary antigen.
Ideally the intestinal immune system can discriminate proteins in the food stream as
innocuous and not of any pathogenic importance. It can be said in this case that a state of
tolerance is achieved with suppression of IgE and IgG responses, and enhancement of a
local secretory IgA antibody response. Certainly, the integrity of the mucosal barrier with its
4. immune constituents in competent interplay is prerequisite for oral tolerance induction, and
susceptibility to breakdown of oral tolerance varies individually. Loss of mucosal barrier
integrity and genetic polymorphisms in markers of innate immunity, including that of the
Fc[gamma]R class of IgG receptors, no doubt play a key role in abrogation of oral tolerance
to dietary challenge. The biological mechanisms of food allergies are diverse and remain to
be explored. Loss of tolerance, as exemplified by elevated food-specific IgG class antibodies
is a breakdown of the GALT to distinguish antigens of non pathogenic importance,
abrogating the metabolic usefulness of the foods we eat, and instigating the potential for
inflammatory and autoimmune conditions.
Effective assessment of food allergies, especially through IgG testing should be as routine
for the practitioner as ordering a CBC (Complete Blood Count). Identification of elevated
food-specific IgG antibodies is a means to identify loss of tolerance to dietary proteins, and
provides the practitioner with a tool to direct care in the appropriate manner. Once identified,
treatment of food allergies includes dietary rotation of compatible foods and avoidance of
allergenic ones, in addition to cogent measures to re-establish tolerance.
The ELISA Method
The ELISA colorimetric technique, or Enzyme-Linked Immunosorbent Assay, is a useful
screen for immediate and delayed food allergies mediated through immunoglobulin E (IgE)
and immunoglobulin G (IgG), respectively. Allergic reactions to foods are characterized by
elevated allergen-specific immunoglobulin serum levels with activation of immune mediators
of inflammation. Food allergies are implicated in intestinal pathology, as typified by celiac
disease, and a number of systemic inflammatory conditions. (21), (22)
ELISA is a quantitative/semiquantitative in vitro analysis designed to detect and quantify IgG
and IgE antibodies reactive to various food proteins. Through the ELISA testing method,
lyophilized food proteins are immobilized by adsorption to plastic wells and reacted with the
serum portion of the individual's blood sample. After washing, the plate is reacted with an
HRP-labeled anti-human IgG or IgE antibody conjugate. The enzyme tag, HRP, or
horseradish peroxidase, facilitates a color change upon addition of its substrate, a
chromagen, to allow for easy detection of antigen-antibody interaction within the wells. The
intensity of the color change is quantified through spectrophotometric analysis, and is
proportional to the concentration of food antigen-specific IgG or IgE antibodies present in the
serum sample.
5. The ELISA Method--Reproducible, Reliable and Valid
There are several industry standards that should be considered for ELISA testing to allow its
implementation as a routine method suitable for analysis of food allergies. Official criteria for
any bioanalytical method includes clear demonstration of reproducibility and reliability for its
intended use based on guidelines set by CLIA (Clinical Laboratory Improvement
Amendments) Requirements for Analytical Quality. (23) Moreover, a laboratory implementing
ELISA methodology for the detection of IgG and IgE food-specific antibodies must clearly
identify its suitability for this purpose in yielding reproducible and consistent results for each
patient tested on every occasion. Reproducibility as the name implies, is the ability of the
test to reproduce the same test results for identical samples under identical test conditions.
Identical testing conditions must be assured by the laboratory through day-to-day and run-to-
run, for a dependable test, or a correct and precise testing procedure that has been exactly
defined. Duplicate testing for example, provides an internal measure of control and assures
reproducibility. If the testing method is precise there should be minimal variation between the
duplicate runs. In addition to this, daily in-house blinded split sample reproducibility checks
are on the onus of the lab and constitute good laboratory practice for quality assurance.
Most often a laboratory also participates in periodic blinded testing through an approved
accredited organization to further insure reproducibility of test results. These strict quality
measures guarantee repeatability of the results; namely the presence of food-specific
IgE/IgG antibodies will be consistently detected each and every time the patient's serum
sample is tested.
In order for a laboratory to provide its testing services, it must hold a license and abide by
federal CLIA rules, the governing body for analytical proficiency testing criteria for
acceptable analytical performance. The purpose of CLIA is to promote good laboratory
practices and to assure a reliable test with reproducible and consistent results. Under the
government of CLIA, a diagnostic laboratory has demonstrated and documented
participation in proficiency testing and quality assurance and control. CLIA certification and
accreditation requires that the laboratory be inspected by a CLIA accredited non profit
organization, and approved by the federal Centres for Medicare and Medicaid Services
(CMS), formerly HCFA (Health Care Finance Administration). Inspections for this certification
may be completed through COLA (Commission of Laboratory Accreditation) or CAP (College
of American Pathologists), and are often more rigorous than CLIA regulations. CLIA governs
all laboratory operations including; accreditation, proficiency testing, quality assurance,
quality control, records and information systems, test methods, equipment, and
6. instrumentation. Regulations set under these operations are designed to assure reliability
and consistency of laboratory test results. In the strictest sense, a laboratory must establish
and follow CLIA procedures for monitoring and evaluating the quality of the analytical testing
process to assure reliability; a true and reputable test result. However, it is the responsibility
of the laboratory in compliance with federal quality standards established by CLIA, to assure
reliable laboratory results and documentation/records. More so, it is the responsibility of the
health care practitioner to understand these criteria and to seek a reputable testing facility.
For ELISA food allergy testing to be valid it must accurately measure what it purports to
measure, namely food-specific IgG and IgE antibodies. Only in this way can it be of any
clinical worth to the practitioner and patient. With respect to accuracy, accuracy expresses
the closeness, or degree of agreement between a measured and established reference
value. What, however, defines the established reference value as that which to compare?
The presumption is that there is a true "gold standard" or an accepted method to which a
new method can and should be compared to define its accuracy and hence, credibility. With
respect to IgG food allergy testing, there is no "gold standard" or accepted method available
to define all others. Is IgG ELISA food allergy testing therefore accurate? It can be argued
that this testing method is accurate if it yields similar results to that obtained from another lab
using the same sample. However, each lab abides by their own in-house validation and
quality assurance measures, which may vary from lab to lab. Strictly, this implies that the
results from one laboratory cannot be compared justly to that of another lab, again because
there is no "gold standard" for quantification. The onus of responsibility to provide the
practitioner and patient with a valid IgG food allergy test therefore lies in the hands of the
laboratory to uphold good laboratory practices in compliance with specific federal quality
standards established by CLIA.
Validity is the predictive significance of a test for its intended purpose. That is, the correlation
between the test results and some criterion to which this test is supposed to predict. In
laboratory medicine this criterion refers to a disease state or condition. In conventional
circles the validity of a test is justified by its positive predictive value (PPV). That is, a
remarkable or positive test result will identify a particular diseased state in a large proportion
of the population, with defined signs and symptoms. A true relationship between the PPV
and the prevalence of the disease/condition in the population represents the diagnostic
value of the test and hence its worth. That is, the test when applied to the general population
can efficiently identify those individuals who are likely to have the disease in question while
excluding those unaffected. The diagnostic efficiency of the test is improved by utilizing it
7. only in patients with clear clinical features suggestive of the disease. Two major factors in
improving the diagnostic worth of the test are sensitive and specific achievement. Test
sensitivity is defined as the percentage of people in the population with the disease state in
question that have a remarkable test result. The specificity on the other hand, is defined as
the percentage of people in the population without the disease who have a normal test
result. Ideally, the specificity of a test with regards to the general population should be equal
to 97.5% with 2.5% representing "false positives." It is important to note however, that it is
often difficult to reliably define sensitivity and specificity for a particular test, in part because
of the challenge involved in defining the "reference population" on which to deduce a true
generalization for the population at large. In addition, to what criteria do we define the
presentation of the disease in question to justify its predictive value for substantiating test
validity? This question needs to be addressed when considering the validity of IgG food
allergy testing. First and foremost, as with all laboratory testing, it is a prudent assumption
that a test supplement rather than substitute for clinical skills, and careful clinical
assessment. No test should take the place of sound clinical decision-making. In addition, the
clinician should understand the factors that influence the reliability of the test as such to
guide valid decisions for patient care.
The purpose of IgG ELISA food allergy testing is to identify elevated IgG antibody levels to
food antigens from a sample of the patient's serum. An antigen is any substance that is
regarded as foreign by the immune system and therefore capable of stimulating an immune
response. Elevated food-specific IgG antibody levels are understood to represent IgG
immune-mediated allergies to these particular food antigens. An allergy is defined as a
pathological immune reaction to an antigen. With this in mind, allergy should not be defined
solely as an IgE-mediated hypersensitive atopic condition; allergic rhinitis, atopic dermatitis
and asthma. Allergy is any abnormal immune reaction to an allergen that may result in a
broad range of inflammatory responses, and elevated food-specific IgG antibodies may have
far-reaching systemic consequences. It is well established in immunological circles that
Fc[gamma]R polymorphisms play an important role in the pathogenesis of inflammatory
disease. This, in association with the extended half-life of IgG antibodies, make insult
through dietary challenge an important issue in the management of the chronically unwell
patient. Assessment of elevated IgG food-specific antibodies provide a useful tool for
patient-tailored diet therapy as a means to control in part, undue Fc[gamma]R-mediated
effector functions in the patient with receptor polymorphisms that are implicated in disease
susceptibility.
8. Furthermore, one cannot discuss the clinical validity of IgG food allergy testing without
discussing the mechanisms of oral tolerance. Oral tolerance lies at the heart of
immunological theories and is the cornerstone of setting up a reaction or non-reaction
against self and non-self (dietary challenge). It has been argued that oral tolerance to dietary
antigens is the B cell switching from IgE/IgG antibody production to IgA, under the influence
of a novel cytokine profile.
Abrogation of tolerance to otherwise innocuous food proteins may be involved in the
pathogenesis of a variety of disease states. Loss of mucosal barrier integrity, excessive
stimulation of antigen presenting cells, favor overstimulation of Th cells, and a cytokine
profile that is incompatible with induction of tolerance. (24) This loss of tolerance is the
model of a variety of pathologies from autoimmune-based disease to food allergies and
enteropathies; the mechanisms of which are in the forefront of clinical research today.
Mucosal Tolerance
Mucosal tolerance represents the most important response to food antigens that affords
systemic hyporesponsiveness or protection from inflammatory events and bodily disorder. A
tolerogenic response to dietary challenge is critical to allow for competent digestion and
absorption of nutrients for maintenance of normal structure and function of the body. Loss of
tolerance on the other hand, is the unfavorable immune reaction with hyperresponsiveness
to daily dietary challenge. As a result, mediators for enhanced inflammation and tissue
damage, both local and systemic, predominate with sequelae both acute and chronic.
Moreover, hypersensitivity to ingested foods, IgG and IgE-mediated food allergies, signifies
loss of oral tolerance. Celiac disease for example, is loss of tolerance to wheat gliadin, a
prolamine-derived peptide fraction of the cereal protein gluten. Multiple grain allergies result,
with elevated IgG antibodies to other prolamines including that of rye (secalin), and barley
(hordein). This is an abnormal immunemediated and cytotoxic reaction characterized by
partial or total villous atrophy and lymphoid infiltration of the lamina propria. Crohn's disease
and ulcerative colitis also represent inflammatory bowel diseases in which there is a loss of
oral tolerance, namely to commensal bacteria. (25)
From each meal of the day the gut mucosa is bombarded with a myriad of potentially
antigenic food proteins. Likewise, the diverse population of normal bacterial flora in the
intestine poses an additional potential antigenic challenge. Yet, under normal and ideal
circumstances, the body does not react unfavorably to these mucosal antigens. Resident
microbial flora and food proteins result in immunologic silence, or tolerance. How the
9. mucosal immune system is able to define these antigens as pathogenically important and
mount an inappropriate response in any given circumstance in the susceptible individual is
influenced by many factors. In the neonate for instance, improper establishment of oral
immune tolerance may be influenced through genetic makeup, insufficient acquisition of
microflora, (26) early introduction of solid foods, early cessation of breast-feeding, and
maternal transfer of food antigens through the breast milk. (27) In the adult, breach of oral
tolerance may be mediated through medication use; NSAIDs (non-steroidal anti-
inflammatory drugs) and prednisone block oral tolerance induction. (28) Moreover, any
trauma or insult to the protective mucosal barrier that increases permeability may abrogate a
tolerogenic response.
As a clinician, a true understanding of the mucosal immune system of the gastrointestinal
tract and the induction of oral tolerance, or lack thereof to dietary proteins, is key to
developing a clear appreciation for the potential implications of food allergies in systemic
health.
The body employs many mechanisms at the intestinal lumen-mucosa interface to prevent
the induction of hypersensitivity to food proteins. The first level of protection against undue
penetration of oral antigens involves non-immunological factors. These factors play a pivotal
role in mucosal integrity and antigen exclusion and include: tight junctions and basement
membranes that form the cohesive bonding among the mucosal epithelial cells, low luminal
pH, digestive enzymes, peristalsis, mucus, enteric microflora, mucosal surface regeneration
rate, and the glycocalyx. Breach of any of a number of these defense factors, and integrity
loss of the mucosa allows for aberrant antigen handling, and consequent production of
cytokines triggering a number of tissue damaging events.
The intestinal immune system offers a second line of defense against food antigens.
Immunologic responses include local production of secretory IgA (sIgA) antibodies in the
intestine; systemic priming with cell-mediated immunity and the generation of antibodies; or
tolerance to subsequent antigen challenge. It is argued that IgA deficiency may predispose
one to food hypersensitivity as sIgA is believed to serve as a barrier to absorption,
preventing the uptake of food antigens. (29), (30) In addition, early studies rationalize a
systemic decrease in specific IgE and IgG concomitant with a local increase in sIgA as an
integral role in the induction of oral tolerance. (31), (32) The proposed mechanism was
thought to be due to the influence of Th2 cytokines and TGF-[beta] which act to suppress
IgG/IgE B cell differentiation, but at the same time enhance IgA B cell differentiation. In other
words, oral tolerance was believed to be associated with concomitant local IgA immunity.
10. (33) However, the prime importance of sIgA in oral tolerance is not without challenge.
Experimental studies have proven it difficult to induce an IgA antibody response in animals
immunized orally with protein antigens, and under normal circumstances there is negligible
food specific IgA in the intestine. (34), (35) Shi et al, in particular, have demonstrated the
suppression of OVA-specific IgA responses by fed antigen in experimentally bred mice
deficient in Th1 and Th2 cells, but competent in TGF-[beta]-mediated oral tolerance. In other
words, oral tolerance in these mice did not correlate with a concomitant elevation in OVA-
specific IgA. On the contrary, the IgA response was suppressed compared to that observed
in normal BALB/c control mice. (36) The reduction in IgA in other words, paralleled the
reduction of systemic IgG and IgE in oral tolerance. The researchers conclude therefore a
supporting role for Th1 and Th2 cytokines in regulating the induction of IgA immunity.
Contrary to these findings, Kim et al, have shown TGF-[beta] to be co-stimulatory in IgA
production, influencing B cell differentiation into IgA-producing cells. (37)
IgA is the predominant immunoglobulin secreted by the B cells of the gut. Constituting over
70% (38) of all immunoglobulin present in the intestinal mucosa, it obviously plays a key role
in immune exclusion of food antigens as a "default" mucosal B cell response. However, its
position in oral tolerance is less clear. The GALT is exquisitely sensitive to the residing
cytokine milieu of which dysregulation alters mucosal responsiveness. TFG-[beta] and other
immunosuppressive cytokines, including those of Th2, interact to maintain intestinal
homeostasis and nonresponsiveness to innocuous food antigens. TFG-[beta] in particular,
inhibits the proliferation of T and B cells, and decreases the secretion of IgG
immunoglobulins, yet at the same time induces isotype IgA class switching. (39) Clearly,
local IgA immunity alone is unlikely to account for the absence of food hypersensitivities, but
does accompany and serves as a useful backup to other more pivotal immunoregulatory
mechanisms.
The Gastrointestinal Mucosa
When we consider the cellular arrangements in the gastrointestinal system it is amazing how
the epithelial lining of the mucosa, connected by tight junctions, represents the primary
barrier to food antigen entry. The mucosal epithelium, comprised of absorptive cells, mucus
producing goblet cells, intraepithelial lymphocytes (IEL's), and a basal membrane, is the
interface between the external and internal environments of the body, and permits or
excludes entry of various materials, appropriately under ideal conditions.
11. The gastrointestinal mucosa is the largest surface of about 300[m.sup.2] that is in
continuous contact with the external environment. (40) Rightly so, it houses over 60% of
measurable immune parameters including; mesenteric lymph nodes, Peyer's patches (PP),
isolated follicles, lamina propria lymphocytes, and IEL's. These immune components span
the epithelial lining and lamina propria and constitute the gut associated lymphoid tissues
(GALT). GALT is the largest lymphoid organ of our immune system comprising 80% of the
immunoglobulin producing cells in the body and 75% of the entire T cell population, of which
60% is above the basal membrane. (41)
Antigen presentation in the intestinal mucosa includes; B cells, macrophages, and dendritic
cells of which reside primarily in the lamina propria, PP, and mesenteric lymph nodes of the
GALT. (42) Not limited to this repertoire, antigen presentation also occurs via; mucosal T
cells, IEL's, and intraepithelial cells (IEC's). (43) It is clear from this list that antigen sampling
does not solely occur via the M cells overlying PP. All cell types are implicated in the
mechanisms of oral tolerance induction. The competency in antigen presentation, the
dynamics in T cell trafficking, the dose and type of antigen, and changes in the cytokine
milieu of the gut, together influence the antigen-specific T helper pattern activity; either
towards down-regulation of the mucosal immune response to facilitate tolerance, or towards
untoward inflammation.
Other factors influencing the predominant immune response to food antigen include; genetic
background and indigenous gut flora. With regards to the former, celiac disease for example,
is believed to be due in part to aberrant antigen presentation. Over 95% of patients with
celiac disease carry a DQ2 (HLA-DQ2) gene that encodes MHC II markers that present
gliadin to T cells in the lamina propria. (44), (45) Cytokine release increases the expression
of HLA-II, thus amplifying the immune response with resulting cell damage. These
inflammatory mediators also increase gut permeability and promote the differentiation of B
cells into IgG-antigliadin antibody-producing plasma cells. (46)
Indigenous gut microflora has been strongly implicated in competent induction of oral
tolerance. The gastrointestinal tract contains about 100,000 billion, or three and one- half
pounds worth of viable microflora of which there is a variation in number and type in the
different regions of the intestine. (47) Lactobaccilli predominate in the small intestine,
particularly in the middle and distal ileum, whereas Bifidobacteria increase in prevalence
from the cecum to large intestine. Gut microflora are compulsory to the development of
mucosal immuno-responsiveness--humoral and cell-mediated immunity, during the neonatal
period, and serves to prime the GALT throughout the life of the individual. (48) Following
12. birth, in the absence or delay of colonizing microflora, oral tolerance may be abrogated.
Specifically, there is incomplete maturation and development of Peyer's patches,
intraepithelial and lamina propria lymphocytes, in addition to decreased levels of plasma
cells and IgA antibody production. (49) Clearly, defective development of the mucosal
immune system in this way will incite deregulated inflammation and negatively influence the
immune response to dietary antigens.
The mucosal surface represents the interface between the internal and external
environments of the body that is in continual contact with a myriad of food proteins, invasive
pathogens and indigenous flora on a daily basis. Discernment between infectious and
noninfectious agents is therefore key to survival of the individual in his environment. Under
normal circumstances down-regulation of the immune response governs oral tolerance to
dietary antigens and indigenous flora of the gastrointestinal tract. (50), (51) The precise
mechanisms involved in inducing oral tolerance to dietary antigens are imperfectly known. It
is important to keep in mind that oral tolerance is a complex immune response that involves
a precarious balance among several immune-mediated parameters. A glimpse into the
competency of tolerance through IgG food allergy testing via the ELISA method is a simple
tool for the practitioner to visualize the immunological response to dietary challenge in the
patient. In practice, this assessment may guide treatment to nullify undue mediators of
inflammation in the body that may be perpetuating a disease process.
US BioTek Laboratories [c]2004
References
(1.) Bock, S.A., et al. Studies of hypersensitivity reactions to foods in infants and children. J.
Allergy Clin. Immun. 62(6): 327-34, 1978.
(2.) Sampson, H.A., Role of immediate food hypersensitivity in the pathogenesis of atopic
dermatitis. J. Allergy Clin. Immun. 71(5): 473-80, 1983.
(3.) Bock, S.A., et al. Appraisal of skin tests with food extracts for diagnosis of food
hypersensitivity. Clin. Allergy, 8(6): 559, 1978.
(4.) Sampson, H.A., Albergo, R., Comparison of results of skin tests, RAST and double-
blind, placebo-controlled food challenges in children with atopic dermatitis. J. Allergy Clin.
Immunol. 74(1): 26-33, 1984.
13. (5.) Campbell, D.E., et al. Indirect enzyme-linked immunosorbent assay for measurement of
human immunoglobulins E and G to purified cow's milk proteins: application in diagnosis of
cow's milk allergy. J Clin Microbiol. 25(11): 2114-2119, 1987.
(6.) Barrett, K.E., Metcalfe, D.D., The mucosal mast cell and its role in gastrointestinal
allergic diseases. Clin. Rev. Allergy, 2:39-53, 1984.
(7.) Trotsky, Martin, Immunology for the otolaryngic allergist. Otolaryngic Allergy, 25(1): 151-
162, 1992.
(8.) Suen, Raymond, Gordon, Shalima, A critical review of IgG immunoglobulins and food
allergy -implications in systemic health. Townsend Letter for Doctors & Patients,
241/242:134-38, 2003.
(9.) Trotsky, op. cit.
(10.) Shakib, F., The role of antiglobulins in IgG4-mediated allergic diseases. N. Engl. Reg.
Allergy Proc. 9(1); 35-42, 1988.
(11.) Ferguson, A.C., Salinas, F.A., Elevated IgG immune complexes in children with atopic
eczema. J. Allergy Clin. Immunol. 74:678-682, 1984.
(12.) Gessner, J.E., et al. The IgG Fc receptor family. Ann. Hematol. 76(6): 231-48, 1998.
(13.) Van der Pol, W., Van de Winkel, J.G., IgG receptor polymorphisms: risk factors for
disease. Immunogenetics, 48(3): 222-32, 1998.
(14.) Van Sorge, N.M., Van Der Pol, W.L., Van De Winkel, J.G., FcgammaR polymorphisms:
implications for function, disease susceptibility and immunotherapy. Tissue Antigens, 61(3):
189-202, 2003.
(15.) Loos, B.G., et al. Fcgamma receptor polymorphisms in relation to periodontitis. J. Clin.
Periodontol. 30(7): 595-602, 2003.
(16.) Brun, J.G., Madland, T.M., Vedeler, C.A., Immunoglobulin G fc-receptor (FcgammaR)
IIA, IIIA, and IIIB polymorphisms related to disease severity in rheumatoid arthritis. J.
Rheumatol. 29(6): 1135-40, 2002.
14. (17.) Dijstelbloem, H.M., et al. Fcgamma receptor polymorphisms in systemic lupus
erythematosus: association with disease and in vivo clearance of immune complexes.
Arthritis Rheum. 43(12): 2793-800, 2000.
(18.) Kawanishi, H., Saltzman, L.E., Strober, W., Mechanisms regulating IgA class-specific
immunoglobulin production in murine gut-associated lymphoid tissues. I.T cells derived from
Peyer's patches that switch sIgM B cells to sIgA B cells in vitro.'J. Exp. Med.'157(2): 433-
450, 1983.
(19.) Spiekermann, Gerburg, M., Walker, Allan, W., Oral tolerance and its role in clinical
disease. Journal of Pediatric Gastroenterology and Nutrition, 32:237-255, 2001.
(20.) Rousset, F., Garcia, E., Banchereau, J., Cytokine-induced proliferation and
immunoglobulin production of human B lymphocytes triggered through their CD40 antigen. J.
Exp. Med. 173(3): 705-710, 1991.
(21.) Gershwin, Eric, M., German, Bruce, J., Keen, Carl, L., Eds. Nutrition and Immunology:
Principles and Practice. New Jersey: Humana Press, Inc., 2000.
(22.) Suen, op. cit.
(23.) CLIA Requirements for Analytical Quality. Westgard Quality Corporation
http://www.westgard.com/clia.htm
(24.) Brandtzaeg, P., Overview of the mucosal immune system. Current Topics in
Microbiology and Immunology, 146:13-25, 1989.
(25.) Elson, C.O., et al. Experimental models of inflammatory bowel disease.
Gastroenterology, 109(4): 1344-1367, 1995.
(26.) Plummer, Nigel, Oral Tolerance: Revolutionary Implications in Immunological Health
and Disease. Pharmax LLC: Practical Solutions Seminar Series. Bellevue, WA. June 7-8,
2003.
(27.) Gershwin, op. cit.
(28.) Postlethwaite, Arnold, E., Can we induce tolerance in rheumatoid arthritis? Current
Rheumatology Reports, 3:64-69, 2001.
15. (29.) Cunningham-Rundles, C., et al. Milk precipitins, circulating immune complexes, and
IgA deficiency. Proc. Natl. Acad. Sci. 75(7): 3387-3389, 1978.
(30.) Challacombe, S.J., Tomasi, Jr., T.B., Systemic tolerance and secretory immunity after
oral immunization. J. Exp. Med. 152: 1459-1472, 1980.
(31.) Challacombe, op. cit.
(32.) Saklayen, Mohammad, G., et al. Kinetics of oral tolerance: study of variables affecting
tolerance induced by oral administration of antigen. Int. Archs. Allergy appl. Immun. 73:5-9,
1984.
(33.) Challacombe, op. cit.
(34.) Mowat, A.M., Maloy, K.J., Donachie, A.M., Immune-stimulating complexes as adjuvants
for inducing local and systemic immunity after oral immunization with protein antigens.
Immunology, 80(4): 527-534, 1993.
(35.) O'Mahony, S., et al. Dissociation between systemic and mucosal humoral immune
responses in coeliac disease. Gut, 32(1): 29-35, 1991.
(36.) Shi, Hai Ning, Grusby, Michael, J., Nagler-Anderson, Cathryn. Orally induced
peripheral nonresponsiveness is maintained in the absence of functional Th1 or Th2 cells.
The Journal of Immunology, 162:5143-5148, 1999.
(37.) Kim, P.H., Kagnoff, M.F., Transforming growth factor-beta I is a costimulator for IgA
production. J. Immunol. 144(9): 3411-3416, 1990.
(38.) Abreu-Martin, Maria, T., Targan, Stephan, R., Regulation of immune responses of the
intestinal mucosa. Critical Reviews in Immunology, 16:277-309, 1996.
(39.) Nagler-Anderson, Cathryn, Tolerance and immunity in the intestinal immune system.
Critical Reviews in Immunolgy, 20:103-120, 2000.
(40.) Spiekermann, op. cit.
(41.) Plummer, op. cit.
16. (42.) Wardrop, III, R.M., Whitacre, C.C., Oral tolerance in the treatment of inflammatory
autoimmune diseases. Inflamm. Res. 48:106-119, 1999.
(43.) Abreu-Martin, op. cit.
(44.) Balas, A., et al. Absolute linkage of celiac disease and dermatitis herpetiformis to HLA-
DQ. Tissue Antigens, 50(1): 52-56, 1997.
(45.) Godkin, A., Jewell, D., The pathogenesis of celiac disease. Gastroenterology, 115(1):
206-210, 1998.
(46.) Gershwin, op. cit.
(47.) Plummer, op. cit.
(48.) Plummer, op. cit.
(49.) Plummer, op. cit.
(50.) Plummer, op. cit.
(51.) Spiekermann, op. cit.
by Raymond M. Suen, MT (ASCP) and Shalima Gordon, BSc, ND
Correspondence:
Raymond Suen, MT
U.S. Biotek Laboratories
13500 Linden Ave. North
Seattle, Washington 98133 USA