This presentation Prof. Dr. Vladimir Trajkovski: IMUNOGENETIC ANALYSES IN PERSONS WITH AUTISM IN REPUBLIC OF MACEDONIA should presented in conference in Barcelona, but he wasn't there because it was cancelled.
This document provides an overview of multiple sclerosis (MS) models and the challenges of translating findings from animal models to clinical applications. It discusses key aspects of MS like pathogenesis, clinical courses, and neurodegeneration. Common MS models like experimental autoimmune encephalomyelitis (EAE) are described along with their limitations in mimicking the human disease. Issues like preclinical failure to translate findings and limitations of experimental design that can contribute to clinical trial failures are reviewed. Guidelines for improving experimental design and reporting are also mentioned.
This document provides an overview of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), an animal model of MS. It discusses the importance of understanding the biology and clinical course of both MS and EAE to effectively model and translate findings from animals to humans. It highlights challenges with failure to translate preclinical findings, including using models and studies that do not accurately reflect human disease. The document emphasizes the need for rigorous experimental design, reporting, and application of the 3Rs to improve modelling of MS and outcomes of drug development efforts.
Molecular Vision Publication by Anuradha SinghAnuradha Singh
This study identified a novel heterozygous mutation, c.525G>C (Q175H), in the VSX1 gene in one individual with keratoconus out of 66 patients studied. Bioinformatics tools predicted this mutation would be potentially damaging. This adds to evidence that VSX1 plays a role in keratoconus, though its exact pathogenic mechanism requires further investigation given the low frequency of this mutation. This is the first report of a VSX1 mutation identified in keratoconus patients from India.
This document summarizes a presentation on low dose cytokines in supportive cancer therapy. It discusses how low dose cytokines from GUNA S.p.a, such as IL-4, IL-12, and IFN-γ at concentrations of 10 fg/ml, can enhance the antigen presentation and stimulatory activity of dendritic cells obtained from early stage colorectal cancer patients. An ex vivo study found that sequential exposure of these patient's dendritic cells to low doses of IL-4 and IL-12 increased their ability to stimulate T-cell responses compared to treatment with standard doses of cytokines. The presentation concludes that GUNA's approach using low dose cytokines may provide a novel integrated therapy to activate the immune system in cancer.
Benjamin Korman, MD discusses the genetics of scleroderma and the genomic era. Genetics and genomics are complicated, and getting more so every day. Every patient is genetically unique, but new technology will make it easier to understand individuals’ genetic susceptibility to disease and response to therapy.
Sulphasalazine Induced Toxic Epidermal Necrolysis A Case Reportiosrphr_editor
The document describes a case study of an 18-year-old female patient who developed toxic epidermal necrolysis as a severe adverse reaction to the drug sulfasalazine, which she had been taking for ankylosing spondylitis. She was admitted to the intensive care unit and treated with high dose corticosteroids, fluid replacement, and supportive care. She improved with treatment and was discharged with only post-inflammatory hypopigmentation.
This document summarizes 6 case studies of children who experienced fractures, retinal hemorrhages, and brain injuries. In each case, the injuries were initially attributed to non-accidental trauma (such as shaken baby syndrome), but laboratory tests revealed evidence of autoimmune reactions, vitamin deficiencies, and coagulation disorders following vaccination or childhood illness. The document argues that fractures, hemorrhages, and encephalopathy in these cases were actually caused by an autoimmune response to antigenic stimulation from vaccines or infections, rather than abuse.
Vitamin D may have benefits for people with multiple sclerosis (MS). Low vitamin D levels are common in MS and are associated with worse bone health and increased disease activity. Supplementation to raise vitamin D levels has been shown to improve bone mineral density in MS. Some clinical trials also found signals that vitamin D supplementation may reduce MRI lesions and relapse rates. However, the evidence is mixed and high-dose supplementation over long periods may carry risks. Experts recommend MS patients aim to maintain vitamin D levels between 50-100 nM through supplementation as needed. More research is still needed to fully understand the role and optimal dosing of vitamin D in MS.
This document provides an overview of multiple sclerosis (MS) models and the challenges of translating findings from animal models to clinical applications. It discusses key aspects of MS like pathogenesis, clinical courses, and neurodegeneration. Common MS models like experimental autoimmune encephalomyelitis (EAE) are described along with their limitations in mimicking the human disease. Issues like preclinical failure to translate findings and limitations of experimental design that can contribute to clinical trial failures are reviewed. Guidelines for improving experimental design and reporting are also mentioned.
This document provides an overview of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), an animal model of MS. It discusses the importance of understanding the biology and clinical course of both MS and EAE to effectively model and translate findings from animals to humans. It highlights challenges with failure to translate preclinical findings, including using models and studies that do not accurately reflect human disease. The document emphasizes the need for rigorous experimental design, reporting, and application of the 3Rs to improve modelling of MS and outcomes of drug development efforts.
Molecular Vision Publication by Anuradha SinghAnuradha Singh
This study identified a novel heterozygous mutation, c.525G>C (Q175H), in the VSX1 gene in one individual with keratoconus out of 66 patients studied. Bioinformatics tools predicted this mutation would be potentially damaging. This adds to evidence that VSX1 plays a role in keratoconus, though its exact pathogenic mechanism requires further investigation given the low frequency of this mutation. This is the first report of a VSX1 mutation identified in keratoconus patients from India.
This document summarizes a presentation on low dose cytokines in supportive cancer therapy. It discusses how low dose cytokines from GUNA S.p.a, such as IL-4, IL-12, and IFN-γ at concentrations of 10 fg/ml, can enhance the antigen presentation and stimulatory activity of dendritic cells obtained from early stage colorectal cancer patients. An ex vivo study found that sequential exposure of these patient's dendritic cells to low doses of IL-4 and IL-12 increased their ability to stimulate T-cell responses compared to treatment with standard doses of cytokines. The presentation concludes that GUNA's approach using low dose cytokines may provide a novel integrated therapy to activate the immune system in cancer.
Benjamin Korman, MD discusses the genetics of scleroderma and the genomic era. Genetics and genomics are complicated, and getting more so every day. Every patient is genetically unique, but new technology will make it easier to understand individuals’ genetic susceptibility to disease and response to therapy.
Sulphasalazine Induced Toxic Epidermal Necrolysis A Case Reportiosrphr_editor
The document describes a case study of an 18-year-old female patient who developed toxic epidermal necrolysis as a severe adverse reaction to the drug sulfasalazine, which she had been taking for ankylosing spondylitis. She was admitted to the intensive care unit and treated with high dose corticosteroids, fluid replacement, and supportive care. She improved with treatment and was discharged with only post-inflammatory hypopigmentation.
This document summarizes 6 case studies of children who experienced fractures, retinal hemorrhages, and brain injuries. In each case, the injuries were initially attributed to non-accidental trauma (such as shaken baby syndrome), but laboratory tests revealed evidence of autoimmune reactions, vitamin deficiencies, and coagulation disorders following vaccination or childhood illness. The document argues that fractures, hemorrhages, and encephalopathy in these cases were actually caused by an autoimmune response to antigenic stimulation from vaccines or infections, rather than abuse.
Vitamin D may have benefits for people with multiple sclerosis (MS). Low vitamin D levels are common in MS and are associated with worse bone health and increased disease activity. Supplementation to raise vitamin D levels has been shown to improve bone mineral density in MS. Some clinical trials also found signals that vitamin D supplementation may reduce MRI lesions and relapse rates. However, the evidence is mixed and high-dose supplementation over long periods may carry risks. Experts recommend MS patients aim to maintain vitamin D levels between 50-100 nM through supplementation as needed. More research is still needed to fully understand the role and optimal dosing of vitamin D in MS.
1. Klaus Schmierer presents disclosures related to research funding and speaking engagements from various pharmaceutical companies involved in multiple sclerosis treatment.
2. He discusses two important lessons about MS treatment - that the disease is progressive from the start, and patients have a better chance of avoiding disability if treated early.
3. Selective immune reconstitution therapy (SIRT) and treatments like alemtuzumab and cladribine that deplete memory B cells have been shown to be highly effective at controlling disease activity, with alemtuzumab demonstrating similar efficacy to cladribine but with different adverse effect profiles.
Prediction of outcome of Multiple sclerosisAmr Hassan
Prediction of outcome of Multiple sclerosis
An understanding of the natural history of multiple sclerosis(MS) in a patient is important to begin proper treatment at the correct time, especially when there is a high risk for poor prognosis. Factors that predict unfavorable prognosis are a primary or secondary progressive course, older age at disease onset, short interval between first and second attacks, initial cerebellar or pyramidal symptoms, a large number of functional systems involved at onset, moderate to severe disability within the first 2 years, and the presence of typical plaques or greater lesion volume shown by magnetic resonance imaging results during the first 5 years. However, there are no established laboratory tests able to predict long-term prognosis.
Can brain atrophy measurement help us in monitoring MS progression in routine...MS Trust
This presentation by Dana Horáková, Department of Neurology and Centre of Clinical Neuroscience at the Charles University in Prague, looks at why and how we should measure brain atrophy.
It was presented at the MS Trust Annual Conference in November 2014.
MRI Workshop
Dr. Ben Turner held an MRI workshop in November 2018. He discussed the principles of magnetic resonance imaging, different MRI techniques like T2 imaging and flair images, and how MRI is beneficial but also has drawbacks for monitoring multiple sclerosis. MRI is most useful for research, diagnosis, therapeutic innovation for drug trials, and monitoring therapies. New diagnostic criteria for multiple sclerosis were also presented, focusing on dissemination of lesions in space and time with no better explanation. Factors like lesion number and location provide prognostic information about progression.
Cadth 2015 c1 coles canada cadth presentationCADTH Symposium
This document discusses the treatment of a 19-year-old female law student and marathon runner with multiple sclerosis who had an inadequate response to interferon beta. It considers evidence from real-world databases and indirect treatment comparisons to help guide switching to alternative treatments like fingolimod or natalizumab. It also describes the patient's choice and good response to the more aggressive therapy alemtuzumab, which was later approved for use in the UK based on evidence of greater effectiveness and lower costs compared to other treatments.
This document summarizes the London experience with autologous hematopoietic stem cell transplantation (AHSCT) for multiple sclerosis (MS). It provides data on 54 patients who underwent AHSCT, with a median follow up time of 23 months. Complications included admissions to the intensive care unit and re-admissions post-transplant, with no treatment related deaths in this group. Outcomes included low rates of relapses, disability progression, and new MRI lesions post-transplant. The results were consistent with prior studies and support further investigation of AHSCT as a treatment for highly active relapsing MS and progressive MS with disease activity. Ongoing trials are exploring whether AHSCT may be superior to
IgG4-related disease is characterized by lymphoplasmacytic infiltration and fibrosis in tissues, with elevated IgG4 levels in serum and tissues. It commonly affects the pancreas, salivary glands and lymph nodes. Histopathological analysis shows a dense lymphoplasmacytic infiltrate organized in a storiform pattern, obliterative phlebitis and mild-to-moderate eosinophil infiltrate. Diagnosis requires correlation of clinical features with pathological findings of increased IgG4+ plasma cells and IgG4+/IgG+ ratios in tissues.
The document summarizes a study that tested a gene therapy treatment approach for Infantile Batten Disease (INCL) in mice. The study administered an AAV vector carrying the CLN1 gene via intrathecal injection to INCL mice at different ages corresponding to disease stages. Mice treated at 4 weeks or earlier showed therapeutic benefits like improved survival and quality of life, with mice treated at 1 week still alive and healthy at 15 months. Treatment after onset of symptoms at 20 weeks or later provided only modest benefits. The results demonstrate the importance of early intervention for gene therapy to be most effective in treating INCL.
Predict of coronary artery lesions in Kawasaki disease (川崎症-郭和昌醫師)Ho-Chang Kuo (郭和昌 醫師)
The document discusses predicting coronary artery aneurysm (CAL) formation in Kawasaki disease (KD). It describes the clinical presentation and diagnostic criteria of KD. Treatment involves high-dose intravenous immunoglobulin (IVIG) and aspirin. Some patients are resistant to initial IVIG treatment. Genetic studies have found associations between certain single nucleotide polymorphisms and susceptibility to KD or CAL formation.
This document summarizes expert opinions on the management of CLN2 disease based on a survey of 23 disease experts. It finds that while guidelines do not exist, management strategies are consistent worldwide. A multidisciplinary approach is critical and should include specialists in neurology, palliative care, genetics, physiotherapy, and patient advocacy. Key aspects of management include seizure control using antiepileptic drugs, management of movement disorders, maintaining nutrition, early palliative care involvement, and addressing sleep, pain, and end-of-life issues. The goals of care evolve over the course of the disease from maintaining function to preserving quality of life as symptoms progress.
This document discusses genetics and precision medicine in Lennox-Gastaut syndrome (LGS). It provides an overview of genetics concepts and terminology. De novo genetic variants are found in over 30% of LGS cases. Many genes can cause LGS, with DNM1 accounting for up to 2% of cases. A genetic diagnosis can enable precision medicine approaches like targeting sodium channel blockers for patients with SCN2A variants. Genetic testing is recommended for understanding and improving treatment of drug-resistant LGS.
Evaluation the efficacy of IVIgG in treatment of Hemolytic Disease of Newborniosrphr_editor
Hemolytic disease of newborn (HDN) is an important cause of hyperbilirubinemia in the
neonatal period,and delayed diagnosis and treatment may lead to permanent brain damage. Traditional
neonatal treatment of HDN is intensive phototherapy and exchange transfusion.Intravenous
immunoglobulin(IVIgG) has been introduced as an alternative therapy to exchange transfusion. This study was
conducted to assess the effect of IVIG in HDN .
This study investigated the role of the complement receptor C5ar1 in epilepsy models. The researchers found that C5ar1 was upregulated in mouse models of status epilepticus. Treatment with the C5ar1 antagonist PMX53 reduced seizures in acute and chronic seizure models. PMX53's anticonvulsant effects were mediated by C5ar1, as they were not seen in C5ar1-deficient mice or with an inactive analogue. Inhibition of C5ar1 during status epilepticus lessened seizures, protected neurons from degeneration, and reduced mortality. The study suggests blocking C5ar1 activation may be a novel target for developing new anti-epileptic drugs.
Emerging therapies in Lennox-Gastaut SyndromeLGS Foundation
Tracy Dixon-Salazar presented on emerging therapies and clinical trials in Lennox-Gastaut syndrome (LGS). There have been several new drugs approved to treat LGS, including perampanel and cannabidiol, which have shown efficacy in reducing seizure frequency. A Phase 3 clinical trial is underway to evaluate the effectiveness of fenfluramine for controlling seizures in LGS patients. While treatment options have expanded, LGS remains difficult to treat as evidence for any single highly effective therapy is still limited.
This document provides an overview of gene therapy presented by Vishnu Kumar Dhakad. It discusses the history of gene therapy from its origins in 1960 to early clinical trials in 1990. The presentation covers approaches to gene therapy including gene modification, transfer methods using viral and non-viral vectors, and applications to specific cell lines. Examples of successful gene therapy treatments for blindness and Parkinson's disease are provided. The document also notes some advantages and disadvantages of gene therapy as well as ethical considerations surrounding the field.
1) Vitamin B12 deficiency
2) Pernicious anemia
3) Folic acid deficiency
4) Iron deficiency anemia
5) Biermer's disease
a) Megaloblastic anemia
b) Macrocytic anemia
c) Microcytic anemia
d) Combined degeneration of spinal cord
e) Pancytopenia
1 - b
2 - b
3 - a
4 - c
5 - d
STATION - 20 B
Name the investigations for diagnosis of iron deficiency anemia:
Discovered by Eloise Giblett in 1972.
ADA deficiency or ADA-SCID or Bubble boy disorder.
Recognized as the first immunodeficiency disorder.
Accounts for 10-15% of all cases of SCID.
An autosomal recessive metabolic disorder causes immunodeficiency.
Rare occurring disease.
Both males and females are equally affected.
All racial and ethnic groups are affected
GENETIC BASIS OF PSYCHIATRIC DISRODERS AND THE RELEVANCE OF CLINICAL PRACTICEPRASHNATH javali
Presentation regarding the counseling of genetic disorders and the steps involved along with the process of Genetic counseling guidance,way to disclose the results,steps to be taken for the care of mentally ill persons.
This document summarizes a presentation on selective B cell depletion therapies for managing highly active relapsing multiple sclerosis (MS). The presentation discusses:
- Drugs available that selectively deplete B cells including rituximab, ocrelizumab, and ofatumumab.
- Benefits of B cell depletion therapies like avoiding hospital visits during COVID-19, minimal monitoring requirements, and long-term efficacy from short-term treatment.
- Ocrelizumab as the preferred treatment based on its safety profile and 2020 sales of $4.6 billion.
This study assessed whether single nucleotide polymorphisms (SNPs) in the NOS2A gene increase risk for age-related macular degeneration (AMD) and interact with smoking. 998 Caucasian subjects were genotyped for 17 SNPs in NOS2A. Multivariable logistic regression identified that SNP rs8072199 was significantly associated with increased AMD risk. A significant interaction with smoking was detected for rs2248814. Stratified analysis found that the association between AMD and smoking was strongest in carriers of the AA genotype at this SNP compared to AG and GG genotypes, suggesting a possible synergistic interaction between this genotype and smoking. The results provide preliminary evidence that genetic variation in NOS2A may influence AMD risk and
This document summarizes a study of 8 cases of Subacute sclerosing panencephalitis (SSPE) in Iraq. The patients ranged from 7-10 years old. Diagnosis was based on clinical features and detection of measles virus antibodies in cerebrospinal fluid and serum using ELISA and PCR techniques. ELISA showed all 8 patients were positive for measles virus IgG in serum and CSF. PCR also confirmed presence of measles virus genomic DNA in all patients. 5 patients showed evidence of oligoclonal bands in CSF. The study highlights the importance of childhood measles immunization programs in preventing SSPE.
1. Klaus Schmierer presents disclosures related to research funding and speaking engagements from various pharmaceutical companies involved in multiple sclerosis treatment.
2. He discusses two important lessons about MS treatment - that the disease is progressive from the start, and patients have a better chance of avoiding disability if treated early.
3. Selective immune reconstitution therapy (SIRT) and treatments like alemtuzumab and cladribine that deplete memory B cells have been shown to be highly effective at controlling disease activity, with alemtuzumab demonstrating similar efficacy to cladribine but with different adverse effect profiles.
Prediction of outcome of Multiple sclerosisAmr Hassan
Prediction of outcome of Multiple sclerosis
An understanding of the natural history of multiple sclerosis(MS) in a patient is important to begin proper treatment at the correct time, especially when there is a high risk for poor prognosis. Factors that predict unfavorable prognosis are a primary or secondary progressive course, older age at disease onset, short interval between first and second attacks, initial cerebellar or pyramidal symptoms, a large number of functional systems involved at onset, moderate to severe disability within the first 2 years, and the presence of typical plaques or greater lesion volume shown by magnetic resonance imaging results during the first 5 years. However, there are no established laboratory tests able to predict long-term prognosis.
Can brain atrophy measurement help us in monitoring MS progression in routine...MS Trust
This presentation by Dana Horáková, Department of Neurology and Centre of Clinical Neuroscience at the Charles University in Prague, looks at why and how we should measure brain atrophy.
It was presented at the MS Trust Annual Conference in November 2014.
MRI Workshop
Dr. Ben Turner held an MRI workshop in November 2018. He discussed the principles of magnetic resonance imaging, different MRI techniques like T2 imaging and flair images, and how MRI is beneficial but also has drawbacks for monitoring multiple sclerosis. MRI is most useful for research, diagnosis, therapeutic innovation for drug trials, and monitoring therapies. New diagnostic criteria for multiple sclerosis were also presented, focusing on dissemination of lesions in space and time with no better explanation. Factors like lesion number and location provide prognostic information about progression.
Cadth 2015 c1 coles canada cadth presentationCADTH Symposium
This document discusses the treatment of a 19-year-old female law student and marathon runner with multiple sclerosis who had an inadequate response to interferon beta. It considers evidence from real-world databases and indirect treatment comparisons to help guide switching to alternative treatments like fingolimod or natalizumab. It also describes the patient's choice and good response to the more aggressive therapy alemtuzumab, which was later approved for use in the UK based on evidence of greater effectiveness and lower costs compared to other treatments.
This document summarizes the London experience with autologous hematopoietic stem cell transplantation (AHSCT) for multiple sclerosis (MS). It provides data on 54 patients who underwent AHSCT, with a median follow up time of 23 months. Complications included admissions to the intensive care unit and re-admissions post-transplant, with no treatment related deaths in this group. Outcomes included low rates of relapses, disability progression, and new MRI lesions post-transplant. The results were consistent with prior studies and support further investigation of AHSCT as a treatment for highly active relapsing MS and progressive MS with disease activity. Ongoing trials are exploring whether AHSCT may be superior to
IgG4-related disease is characterized by lymphoplasmacytic infiltration and fibrosis in tissues, with elevated IgG4 levels in serum and tissues. It commonly affects the pancreas, salivary glands and lymph nodes. Histopathological analysis shows a dense lymphoplasmacytic infiltrate organized in a storiform pattern, obliterative phlebitis and mild-to-moderate eosinophil infiltrate. Diagnosis requires correlation of clinical features with pathological findings of increased IgG4+ plasma cells and IgG4+/IgG+ ratios in tissues.
The document summarizes a study that tested a gene therapy treatment approach for Infantile Batten Disease (INCL) in mice. The study administered an AAV vector carrying the CLN1 gene via intrathecal injection to INCL mice at different ages corresponding to disease stages. Mice treated at 4 weeks or earlier showed therapeutic benefits like improved survival and quality of life, with mice treated at 1 week still alive and healthy at 15 months. Treatment after onset of symptoms at 20 weeks or later provided only modest benefits. The results demonstrate the importance of early intervention for gene therapy to be most effective in treating INCL.
Predict of coronary artery lesions in Kawasaki disease (川崎症-郭和昌醫師)Ho-Chang Kuo (郭和昌 醫師)
The document discusses predicting coronary artery aneurysm (CAL) formation in Kawasaki disease (KD). It describes the clinical presentation and diagnostic criteria of KD. Treatment involves high-dose intravenous immunoglobulin (IVIG) and aspirin. Some patients are resistant to initial IVIG treatment. Genetic studies have found associations between certain single nucleotide polymorphisms and susceptibility to KD or CAL formation.
This document summarizes expert opinions on the management of CLN2 disease based on a survey of 23 disease experts. It finds that while guidelines do not exist, management strategies are consistent worldwide. A multidisciplinary approach is critical and should include specialists in neurology, palliative care, genetics, physiotherapy, and patient advocacy. Key aspects of management include seizure control using antiepileptic drugs, management of movement disorders, maintaining nutrition, early palliative care involvement, and addressing sleep, pain, and end-of-life issues. The goals of care evolve over the course of the disease from maintaining function to preserving quality of life as symptoms progress.
This document discusses genetics and precision medicine in Lennox-Gastaut syndrome (LGS). It provides an overview of genetics concepts and terminology. De novo genetic variants are found in over 30% of LGS cases. Many genes can cause LGS, with DNM1 accounting for up to 2% of cases. A genetic diagnosis can enable precision medicine approaches like targeting sodium channel blockers for patients with SCN2A variants. Genetic testing is recommended for understanding and improving treatment of drug-resistant LGS.
Evaluation the efficacy of IVIgG in treatment of Hemolytic Disease of Newborniosrphr_editor
Hemolytic disease of newborn (HDN) is an important cause of hyperbilirubinemia in the
neonatal period,and delayed diagnosis and treatment may lead to permanent brain damage. Traditional
neonatal treatment of HDN is intensive phototherapy and exchange transfusion.Intravenous
immunoglobulin(IVIgG) has been introduced as an alternative therapy to exchange transfusion. This study was
conducted to assess the effect of IVIG in HDN .
This study investigated the role of the complement receptor C5ar1 in epilepsy models. The researchers found that C5ar1 was upregulated in mouse models of status epilepticus. Treatment with the C5ar1 antagonist PMX53 reduced seizures in acute and chronic seizure models. PMX53's anticonvulsant effects were mediated by C5ar1, as they were not seen in C5ar1-deficient mice or with an inactive analogue. Inhibition of C5ar1 during status epilepticus lessened seizures, protected neurons from degeneration, and reduced mortality. The study suggests blocking C5ar1 activation may be a novel target for developing new anti-epileptic drugs.
Emerging therapies in Lennox-Gastaut SyndromeLGS Foundation
Tracy Dixon-Salazar presented on emerging therapies and clinical trials in Lennox-Gastaut syndrome (LGS). There have been several new drugs approved to treat LGS, including perampanel and cannabidiol, which have shown efficacy in reducing seizure frequency. A Phase 3 clinical trial is underway to evaluate the effectiveness of fenfluramine for controlling seizures in LGS patients. While treatment options have expanded, LGS remains difficult to treat as evidence for any single highly effective therapy is still limited.
This document provides an overview of gene therapy presented by Vishnu Kumar Dhakad. It discusses the history of gene therapy from its origins in 1960 to early clinical trials in 1990. The presentation covers approaches to gene therapy including gene modification, transfer methods using viral and non-viral vectors, and applications to specific cell lines. Examples of successful gene therapy treatments for blindness and Parkinson's disease are provided. The document also notes some advantages and disadvantages of gene therapy as well as ethical considerations surrounding the field.
1) Vitamin B12 deficiency
2) Pernicious anemia
3) Folic acid deficiency
4) Iron deficiency anemia
5) Biermer's disease
a) Megaloblastic anemia
b) Macrocytic anemia
c) Microcytic anemia
d) Combined degeneration of spinal cord
e) Pancytopenia
1 - b
2 - b
3 - a
4 - c
5 - d
STATION - 20 B
Name the investigations for diagnosis of iron deficiency anemia:
Discovered by Eloise Giblett in 1972.
ADA deficiency or ADA-SCID or Bubble boy disorder.
Recognized as the first immunodeficiency disorder.
Accounts for 10-15% of all cases of SCID.
An autosomal recessive metabolic disorder causes immunodeficiency.
Rare occurring disease.
Both males and females are equally affected.
All racial and ethnic groups are affected
GENETIC BASIS OF PSYCHIATRIC DISRODERS AND THE RELEVANCE OF CLINICAL PRACTICEPRASHNATH javali
Presentation regarding the counseling of genetic disorders and the steps involved along with the process of Genetic counseling guidance,way to disclose the results,steps to be taken for the care of mentally ill persons.
This document summarizes a presentation on selective B cell depletion therapies for managing highly active relapsing multiple sclerosis (MS). The presentation discusses:
- Drugs available that selectively deplete B cells including rituximab, ocrelizumab, and ofatumumab.
- Benefits of B cell depletion therapies like avoiding hospital visits during COVID-19, minimal monitoring requirements, and long-term efficacy from short-term treatment.
- Ocrelizumab as the preferred treatment based on its safety profile and 2020 sales of $4.6 billion.
This study assessed whether single nucleotide polymorphisms (SNPs) in the NOS2A gene increase risk for age-related macular degeneration (AMD) and interact with smoking. 998 Caucasian subjects were genotyped for 17 SNPs in NOS2A. Multivariable logistic regression identified that SNP rs8072199 was significantly associated with increased AMD risk. A significant interaction with smoking was detected for rs2248814. Stratified analysis found that the association between AMD and smoking was strongest in carriers of the AA genotype at this SNP compared to AG and GG genotypes, suggesting a possible synergistic interaction between this genotype and smoking. The results provide preliminary evidence that genetic variation in NOS2A may influence AMD risk and
This document summarizes a study of 8 cases of Subacute sclerosing panencephalitis (SSPE) in Iraq. The patients ranged from 7-10 years old. Diagnosis was based on clinical features and detection of measles virus antibodies in cerebrospinal fluid and serum using ELISA and PCR techniques. ELISA showed all 8 patients were positive for measles virus IgG in serum and CSF. PCR also confirmed presence of measles virus genomic DNA in all patients. 5 patients showed evidence of oligoclonal bands in CSF. The study highlights the importance of childhood measles immunization programs in preventing SSPE.
Subacute sclerosing panencephalitis (SSPE) In Iraqiosrjce
This document summarizes a study of 8 cases of Subacute sclerosing panencephalitis (SSPE) in Iraq. The patients ranged from 7-10 years old. Diagnosis was based on clinical features and detection of measles virus antibodies in cerebrospinal fluid and serum using ELISA and PCR techniques. ELISA showed all 8 patients were positive for measles virus IgG in serum and CSF. PCR also confirmed presence of measles virus genomic DNA in all patients. 5 patients showed evidence of oligoclonal bands in CSF. The study highlights the importance of childhood measles immunization programs in preventing SSPE.
CODAS syndrome is a rare multi-system developmental disorder characterized by cerebral, ocular, dental, auricular, and skeletal anomalies. The researchers identified four mutations in the LONP1 gene in ten individuals with CODAS syndrome from three ancestral backgrounds. LONP1 encodes the mitochondrial Lon protease, which is involved in protein quality control and respiratory complex assembly in mitochondria. The mutations cluster in the AAA+ domain near the ATP-binding pocket and result in defects in ATP-dependent proteolysis. Lymphoblastoid cell lines from affected individuals show swollen mitochondria, aggregated cytochrome c oxidase subunit II, and reduced mitochondrial function, linking LONP1 mutations to CODAS syndrome.
This document describes a study conducted at a neurogenetics clinic in Argentina that aimed to assess the diagnostic yield of evaluating patients with suspected genetic neurological disorders. The study included 387 patients seen between 2008-2014. Overall, a genetic diagnosis was made in 27.4% of patients. When only considering patients that underwent genetic testing, the diagnostic yield was 45%. For the 140 patients evaluated for progressive ataxia, a genetic cause was identified in 23.5% of patients and 57.5% of patients with a positive family history. The most common causes of ataxia identified were spinocerebellar ataxia types 2, 3 and Friedreich ataxia. This study demonstrates that specialized evaluation can provide a
Investigating Shared Additive Genetic Variation for Alcohol DependenceGolden Helix
The document summarizes a study that estimated the SNP-heritability of alcohol dependence in subjects of European and African ancestry. Exploratory and confirmatory factor analysis supported a single factor model of alcohol dependence symptoms that was invariant across ancestries. Genome-wide complex trait analysis estimated significant SNP-heritability for alcohol dependence in both Europeans (h2SNP=0.20) and Africans (h2SNP=0.30), and a large genetic correlation between the groups (rG-SNP=0.76). Future work using Bayesian mixture models could help dissect the genetic variants underlying alcohol dependence heritability across ancestries.
Investigating Shared Additive Genetic Variation for Alcohol DependenceGolden Helix Inc
The document summarizes a study that estimated the SNP-heritability of alcohol dependence in subjects of European and African ancestry. Exploratory and confirmatory factor analyses supported a single factor model of alcohol dependence symptoms that was invariant across ancestries. Genome-wide complex trait analysis estimated significant SNP-heritability for alcohol dependence in both Europeans (h2SNP=0.20) and Africans (h2SNP=0.30), and a large genetic correlation between the groups (rG-SNP=0.76). Future work using Bayesian mixture models could help dissect the genetic variants underlying alcohol dependence heritability across ancestries.
This document discusses opportunities and challenges for developing therapies for ALS. It summarizes that over 25 genes have been linked to ALS risk and describes some of the major genes involved like SOD1, TDP43, FUS and C9orf72. Model systems and pathways identified from genes are providing new treatment targets. There are many drugs and approaches in clinical trials. The document outlines the ALS Association's research strategies like establishing a translational program and consortium initiatives to accelerate drug development. Biomarkers, stem cell models and automated microscopy are providing new tools to study mechanisms and do preclinical testing.
Deletion 17q12 recurrent copy number variant ashadeep chandrareddy daniel d...surabhisupraja
This document summarizes a study that found a recurrent 1.4 Mb deletion at chromosome 17q12 in patients with autism spectrum disorder (ASD) or schizophrenia, but not in controls. The deletion removes the HNF1B gene. In a follow up sample of over 8,000 patients and nearly 48,000 controls, the deletion was identified in patients with ASD/neurocognitive impairment and schizophrenia, but not controls. Clinical assessment of nine patients found features including macrocephaly, characteristic facial features, renal anomalies, and neurocognitive impairments. This provides further evidence that rare copy number variants can contribute to both ASD and schizophrenia, and that one or more genes in the 17q12 region are important
Comuunity acquired listeria monocytogenes meningitis in adultsAlberto Junior
This document summarizes a study of 30 cases of community-acquired Listeria monocytogenes meningitis in adults. The key findings were:
1) All patients were either immunocompromised or over 50 years old. Symptoms were present for over 24 hours in most cases.
2) Typical cerebrospinal fluid findings of bacterial meningitis were absent in some cases. Gram staining revealed the causative organism in less than one-third of cases tested.
3) The initial antimicrobial therapy did not adequately cover L. monocytogenes in nearly one-third of cases. The mortality rate was 17% and nearly one-third had unfavorable outcomes. Inadequate initial therapy was not
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by autoantibodies directed against self-antigens. It can affect many different organs and tissues in the body. Kelsey, a 23-year-old woman, presented with fatigue, joint pain, and a rash. Laboratory tests showed positive ANA, anti-DNA, low complement levels, meeting criteria for SLE. SLE results from genetic and environmental factors interacting to cause immune system dysregulation and loss of self-tolerance. It commonly affects the skin, joints, kidneys, and cardiovascular and pulmonary systems. Timely diagnosis and treatment can help prevent organ damage and disease complications.
Stephan Züchner discusses major developments in human genetics including improved genome sequencing capabilities and declining costs. He summarizes research on inherited axonopathies like hereditary spastic paraplegias and Charcot-Marie-Tooth disease, which are clinically and genetically heterogeneous. Züchner leads a large international collaborative effort called GEM.app involving over 450 investigators that has identified numerous genes for various neurodegenerative and neuromuscular disorders through shared exome and genome data.
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Prof. Dr. Vladimir Trajkovski - IMUNOGENETIC ANALYSES IN PERSONS WITH AUTISM IN REPUBLIC OF MACEDONIA
1. UNIVERSITY „ST. CYRIL AND METHODIUS“ - SKOPJE
FACULTY OF PHYLOSOPHI - SKOPJE
INSTITUTE FOR SPECIAL EDUCATION AND REHABILITATION
IMUNOGENETIC ANALYSES IN
PERSONS WITH AUTISM IN
REPUBLIC OF MACEDONIA
Vladimir Trajkovski, M.D, Ph.D.
Barcelona
11.01.2003
2. 2
INTRODUCTION
• Autism is a developmental disorder of unknown etiology
characterized by severe communication, social, and
behavioral abnormalities.
• A number of factors have been implicated in the pathogenesis
of autism including, genetic, environmental, and
immunological factors.
• Immunologic evaluation of autistic children showed:
− depressed lymphocyte proliferation to mitogens,
− impaired cellular immunity of macrophages and NK cells,
− circulating autoantibodies against putative serotonin brain
receptors, myelin basic protein, glial fibrillary acid protein
and neuron-axon filament proteins,
− elevation of T-cell activation antigens such as soluble
interleukin-2, and soluble CD8,
− increased levels of DR+ activated T cells,
− the levels of IL-12 and IFN-γ are selectively elevated,
− alterations in serum immunoglobulin classes and subclasses,
− increased frequency of the C4B null allele and linkage to
3. 3
AIMS AND TASKS OF THE STUDY
1.Establishing the immunogenetic
structure - HLA-DNA typization of
persons with autism and their families;
2.Determination the level of
immunoglobulin classes and subclasses
in the serum;
3.Studying the specific allergic antibodies
in the serum.
4. 4
MATERIAL AND METHODS
• 50 persons with autism have been analyzed with
existing data in the Institute for Mental Health in
Skopje, Institute for Rehabilitation of Hear, Speech and
Voice in Skopje, Special Institute in Demir Kapija,
Special School „Dr. Zlatan Sremac“ in Skopje, Centers
for Social Work and Medical Centers in Macedonia.
• Blood has been taken for immunogenetic and
immunological analyzes from 35 persons with autism,
22 their biological brothers/sisters, 27 mothers and 23
fathers, as well from 98 healthy unrelated persons.
• Immunogenetic and immunological analyses have been
organized and made at the laboratories of the Institute of
Immunobiology and Human Genetics, Medical Faculty
in Skopje.
• DSM-IV and ICD-10 criteria was established by at least
two psychiatrists made diagnosis of infantile autism.
5. 5
MATERIAL AND METHODS
• Ten milliliters of venous blood was drawn from each donor
by the standard venipuncture in vacutaners with EDTA (K3).
At the time of blood drawing, none of autistic children were
receiving any medication or antipsychotic drug. Plasma
samples were separated by centrifugation and stored at –200
C
till the determination.
• Genomic DNA was extracted from whole blood using
standard proteinase K digestion method followed by salting-
out extraction and ethanol precipitation.
• HLA DNA typing was performed with high resolute
techniques established on 13th International
Histocompatibility Working Group.
• HLA DNA typing of class I genes (HLA-A, -B, and -C) was
performed using a Reverse Line Strip method (RLS), and the
Sequencing Based Typing method (SBT) was used for
6. 6
MATERIAL AND METHODS
• Serum specific allergens from the food (f76 alfa-
lactalbumin, f77 beta-lactglobulin, f78 casein, f79
gluten, f98 gliadin) have been determined with
automatic immunofluorescent devise with solid
phase called Pharmacia UniCAP 100.
• Serum immunoglobulin classes (IgA, IgG, IgM and
IgE) and subclasses (IgG1, IgG2, IgG3 and IgG4) are
determined immunonephelometric by automated
Dade-Behring Nephelometer Analyzer.
• The survey is realized in the period between the
April 2000 to the April 2002 year on the territory of
the Republic of Macedonia.
7. 7
MATERIAL AND METHODS
• The research data have been stored, classified and
processed with standard statistical programme SPSS for
Windows 7.5 version and Statgraphics Plus for
Windows 2.1 version.
• Descriptive statistic methods used in the study are:
central tendencies measures, variability and percentages.
• The differences between numeric variables have been
analyzed with Student’s t-test.
• Nonparametric tests of Kolmogorov-Smirnov, Mann-
Whitney and Kruskal-Wallis have been used in
asymmetric statistical distribution of data.
• Statistical analysis was performed with Arlequin v.2.000
software kindly provided by Excoffier and Slatkin. This
program calculated HLA-A, -C, -B, and –DRB1 allele
frequencies, haplotype frequencies.
• P values of 0.05 or less were considered significant.
9. 9
Country / Author Prevalence
Macedonia 0.25 / 10.000 (2002)
Trefferet et al. 0.7 / 10.000 (1970)
Honda et al.- Japan 21.1 / 10.000 (1996)
Japan - 21.610 1.3 / 1.000 children 3 years
England, Sweeden,
Danmark, France and USA
4 - 5 / 10.000
Bryson,Gilberg, Costello 10 / 10.000
New Scotland - 20.800 1/1.000 (children 6-14 years)
Rapin (Sweeden) 1-2/1.000 (children 3-17 years)
Croatia(Shvel) 7 / 10.000 (1986)
RESULTS
10. 10
RESULTS
PrevalencePrevalence
− The most comprehensible epidemiological study is Eric
Fombonne’s, where the author elaborates 23
epidemiological studies published on English from all
around the world in the period between 1966 and 19981966 and 1998.
In these studies have been included four million people,
from which 1533 persons1533 persons with autism. The estimation
of prevalence is in the range from 0,7 to 21 / 10.000,
with median value of 5,2/ 10.000 children.5,2/ 10.000 children.
− The rate of prevalence for preschool children is
estimated in 5 studies and it is 0,81, for school children
in 11 studies with value of 1,30 and rate of 0,99 for
adolescents estimated in 7 studies;
11. RESULTS
Gender
Male
72%
Female
28%
Coefficient of sex ratio is 2.5 male on 1 femaleCoefficient of sex ratio is 2.5 male on 1 female
person.person.
Gillberg C, Wing LGillberg C, Wing L (1999) male gender is more(1999) male gender is more
frequently affected compared to female (2.1:1 dofrequently affected compared to female (2.1:1 do
3.9:1);3.9:1);
FombonneFombonne (1999), male/female sex ratio varied from(1999), male/female sex ratio varied from
1.33 to 16.0 : 1 with median value 2.6.
12. Age
Median age in our study is 10 years.
Mean age of 10.8 years (SD = 5.77) is very similar
with French epidemiological study of Fombonne et
al., where mean age of the children with autism is
11.6 years (SD = 2.6).
4
13 13
5
2 2
0
2
4
6
8
10
12
14f
0-4 5-9 10-14 15-19 20-24 25-29
14. 14
− The genes of HLA system are located on the short arm of 6th
chromosome (6p 21);
− The genes of HLA cover 3500 kb pairs of DNA;
− The human extended MHC cover a distance of 4
centimorgans of DNA (the frequencies of Crossing-over
within MHC is 4% in each meiosis).
− Several different HLA class I and class II genes encode
proteins with different ranges of abilities to bind pathogenic
peptides.
− The HLA is highly polymorphic (there are multiple forms-
alleles of an HLA gene.
− MHC genes and antigens are separated into 3 classes of
HLA:
class I: HLA-A, HLA-B, HLA-C
class II: HLA-DR, HLA-DP, HLA-DQ
class III: C2, BF, C4A and C4B
Structure of HLA molecules and genes
15. 15
Class II
B2 A2 B1 A1 A B B2 A2 B1 A1 B1 B2 B3 B4 B5 A
DP DN DQ DR
Class III
21B C4B 21A C4A Bf C2 A B B C E A G F
Class I
HLA system: The loci contents functional genes (black
rectangles) and pseudogenes (white rectangles).
16. 16
NS1.119 (12.9)23 (11.7)A*03
NS0.5718 (25.7)74 (37.7)A*02
70 (100.0)196 (100.0)Total
NS1.605 (7.1)9 (4.6)A*68
NS01 (0.5)A*66
NS5.742 (2.9)1 (0.5)A*33
NS0.452 (2.9)12 (6.1)A*32
NS2.831 (1.4)1 (0.5)A*31
NS1.411 (1.4)2 (1.0)A*30
NS0.551 (1.4)5 (2.5)A*29
NS0.552 (2.9)10 (5.1)A*26
NS1.892 (2.9)3 (1.5)A*25
NS1.8013 (18.6)22 (11.2)A*24
NS1.411 (1.4)2 (1.0)A*23
NS1.707 (10.0)12 (6.1)A*11
NS0.876 (8.6)19 (9.7)A*01
pOdds
ratio
OR
AF
N (%)
autism
AF
N (%)
control
HLA-A
alleles
HLA-A allele frequencies in persons with autism and control
subjects.
17. 17
0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%
allele frequencies
A*01 A*02 A*03 A*11 A*23
A*24 A*25 A*26 A*29 A*30
A*31 A*32 A*33 A*66 A*68
autism
control
HLA-A allele frequencies in persons with autism and
control subjects.
18. 1870 (100.0)196 (100.0)Total
NS03 (1.5)C*17
NS1.892 (2.9)3 (1.5)C*16
NS0.935 (7.1)15 (7.6)C*15
NS1.815 (7.1)8 (4.1)C*14
NS1.2814 (20.0)32 (16.3)C*12
NS8.733 (4.3)1 (0.5)C*08
NS0.5612 (17.1)53 (27.0)C*07
NS2.206 (8.6)8 (4.1)C*06
NS2.7108 (4.1)C*05
NS0.596 (8.6)27 (13.8)C*04
0.032.74*9 (12.9)10 (5.1)C*03
NS0.876 (8.6)19 (9.7)C*02
NS0.612 (2.9)9 (4.6)C*01
pOdds ratio
OR
AF
N (%)
autism
AF
N (%)
control
HLA-C
Alleles
HLA-C allele frequencies in persons with autism and control subjects.
19. 19
0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%
allele frequencies
C*01 C*02 C*03 C*04 C*05
C*06 C*07 C*08 C*12 C*14
C*15 C*16 C*17
autism
control
HLA-C allele frequencies in persons with autism and control
subjects.
∗
22. 22
HLA-DRB1 allele frequencies in persons with autism and control
subjects.
70 (100.0)196 (100.0)Total
NS0.6110 (14.3)38 (19.4)DRB1*16
NS1.019 (12.9)25 (12.7)DRB1*15
NS2.443 (4.3)6 (3.1)DRB1*14
NS1.287 (10.0)18 (9.2)DRB1*13
NS03 (1.5)DRB1*12
NS0.8617 (24.3)47 (24.0)DRB1*11
NS2 (2.9)0DRB1*10
NS01 (0.5)DRB1*09
NS06 (3.1)DRB1*08
NS0.854 (5.7)13 (6.6)DRB1*07
NS0.543 (4.3)15 (7.6)DRB1*04
NS1.005 (7.1)14 (7.1)DRB1*03
0.0123.10*10 (14.3)10 (5.1)DRB1*01
pOdds ratio
OR
AF
N (%)
autism
AF
N (%)
control
HLA-
DRB1
allele
23. 23
HLA-DRB1 allele frequencies in persons with autism and
control subjects.
0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%
allele frequencies
DRB1*01 DRB1*03 DRB1*04 DRB1*07 DRB1*08
DRB1*09 DRB1*10 DRB1*11 DRB1*12 DRB1*13
DRB1*14 DRB1*15 DRB1*16
autism
control
∗
24. 24
Frequencies of most frequent haplotypes in persons with
autism and control subjects.
NS03 (1.5)A*11-C*12-B*52-DRB1*16
NS03 (1.5)A*02-C*06-B*13-DRB1*07
NS04 (2.0)A*02 C*07 B*18 DRB1*11
NS06 (3.1)A*01-C*07-B*08-DRB1*03
NS2 (2.9)0A*11-C*03-B*55-DRB1*14
NS2 (2.9)0A*24-C*03-B*55-DRB1*16
NS2 (2.9)0A*11-C*12-B*52-DRB1*15
p
HF
N (%)
autism
HF
N (%)
control
Haplotype
25. 25
DISCUSSION
− Stubbs and Magenis (1980) are the first who speak about the
association between autism and HLA. They have found
increased frequency of HLA-A10 antigen in 10 fathers of
children with autism.
− Reed Warren has found an amino acid sequence in the genes
of the MHC that is expressed more frequently in autistic
subjects than in controls. This sequence is responsible for
development of immunological response towards antigens
and it’s the major connection with other autoimmune
diseases.
− Reed Warren and Daniels report that extended haplotype
B44-SC30-DR4 is found in 40% of autistic subjects and their
mothers, opposite to 2% in control group;
− The third hyper variable region of DRB1 allele has strong
association with autism. HVR-3 DRB1*0401, DRB1*0404
and DRB1*0101 alleles are present in 23 from 50 (46%)
autistic subjects, compared to 6 from 79 (7.5%) normal
subjects.
26. 26
DISCUSSION
Stubbs et al. (1985) determined the HLA types of the parents
of 52 autistic probands. They found increased sharing of at
least one antigen among parents versus a control group from
the literature (75 versus 22 per cent).
Rogers et al. (1999) made linkage analysis, using genetic
marker loci in HLA region at multiplex families with autism.
They examined sharing of alleles identical by descent in 97
affected sib pairs from 90 families. Their results
demonstrated no deviation from the null expectation of 50%
sharing of alleles in this region.
Torres et al. (2002) have evaluated possible contributions of
HLA-DRB1 alleles to autism in 103 families of Caucasian
descent. The TDT indicated that autistic probands inherited
the DRB1*04 allele more frequently than expected (p=0.026)
from the fathers and they found protective association with
DRB1 *13 and *14 alleles.
30. 30
Concentration of immunoglobulines in male and female
persons with autism
NS0.58±0.370.78±0.45IgG4
NS0.43±0.210.46±0.19IgG3
NS2.78±1.612.41±0.94IgG2
NS9.41±2.418.06±2.57IgG1
NS14.54±4.0213.04±3.99IgG
NS1.44±0.491.35±1.12IgM
NS2.00±1.151.44±0.72IgA
pFemale (n=8)Male (n=20)g/L
RESULTS
31. 31
Differences in concentration of Ig classes and subclasses
between Gupta et al. (1996) and our results
0
1
2
3
4
5
6
7
8
9
IgM IgA IgG1 IgG2 IgG3 IgG4
Trajkovski et al.
Gupta et al.
RESULTS
∗
∗
∗
∗
p<0.001 p<0.001p<0.002 p<0.009
32. 32
DISCUSSION
→Plyoplys AV, Greaves A, Yoshida W. (1989) didn’t
find abnormally increased concentrations of
immunoglobulins in the serum.
→Ferrari et al. (1988) found elevated IgG, IgM and IgA
antibody-titres in the serum of autistic patients, although
significance was only reached for IgG-titers.
→Gupta et al. Found in 20% of patients IgA deficiency
and low plasma levels of IgG subclass, but they didn’t
make inferential statistics.
→In our study children with autism have significantly
elevated values of IgG4 (p<0.02) compared to their
healthy brothers and sisters.
→Increased plasma level of IgG4 in the children with
autism could be connected with increased autoimmunity
and/or allergies in this children.
38. 38
Plasma concentration of specific allergic IgA
antibodies (kU/L)
1.67±0.891.76±0.691.37±0.801.55±0.81f98 gliadin
1.21±0.35†
1.27±0.51†
1.44±1.02*2.10±1.94*†
f78 casein
1.26±0.481.33±0.601.10±0.22*1.25±0.45*f77 beta-
lactglobulin
1.17±0.351.24±0.501.10±0.201.19±0.38f76 alfa-
lactalbumin
Father
n=23
Mother
n=27
Brothers-
sisters
n=22
Autism
n=35
Allergens/
IgA
concentration
Values are expressed as mean± SD; p-significance of differences
between persons with autism, brothers/sisters, mother and father
†
40. 40
Plasma concentration of total IgE antibodies (kU/L)
43.628.6†
27.85&
50.7&†
Median value
3523.0831.0125.03652Maximal value
4.73.852.03.37Minimal value
Father
n=23
Mother
n=27
Brothers
-sisters
n=22
Autism
n=35
Total IgE
antibodies
(kU/L)
Values are expressed as mean± SD; p-significance of
differences between persons with autism, brothers/sisters,
mother and father; (&
p < 0 . 0 2); (†
p < 0 . 0 4).
41. 41
DISCUSSION
• Reichelt et al. (1991) in 12 from 44 patients found high levels of
IgA antibodies against casein, gliadin and gluten. This results
confirm the hypothesis that excreted peptides in urine of patients
with autism are from the food. With elimination of gluten and
casein from the food (diet), they noticed improvement in
simptomatology, such as: decreased hyperactivity, increased
attention and concentration, better understanding, interest in new
activities and as well improvement in speech.
• Cade et al. report high titer of IgG antibodies against gliadin
found in 87% of patients with autism and 86% with
schizophrenia and high titer of IgG antibodies against casein
found in 90% of patients with autism and 93% of patients with
schizophrenia. High titer of IgA antibodies against gluten or
casein was found in 30% of children with autism, while 86% of
patients with schizophrenia had increased levels of IgA
antibodies against gluten and 67% against casein. Gluten/casein
free diet which was conducted by these authors shown
improvement in behavior in 81% of children with autism.
42. 42
• Plasma concentration of IgG antibodies against alfa-
laktalbumin, beta-lactoglobulin and casein is statistically
significant higher in autistic persons compared to their
parents (p < 0.001). This is according to high percentage
of patients who had specific IgG antibodies against
casein (Lucarelli et al.).
• Concentration of IgG antibodies against gliadin in
persons with autism was statistically significant higher
than the concentrations in fathers and mothers (p <0.04),
similar to findings of Cade et al.
• The finding of statistically significant higher
concentration of specific allergic IgG antibodies in
persons with autism compared to all control groups is
directly connected with finding of higher IgG4 subclass
concentration which shows involvement of allergies in
etiopathogenesis of the syndrome.
43. 43
• Mean value of plasma concentration of IgA antibodies
against beta-lactoglobulin in persons with autism shown
to be statistically significant higher compared to their
brothers and sisters (p < 0.05).
• The level of casein IgA antibodies in autistic group, also
shown statistically significant higher compared to
control group of fathers and mothers (p < 0.01) and
brothers/sisters (p < 0.05).
• This finding is very similar with results of Lucarelli et
al. who found higher levels of IgA against casein,
lactalbumin, beta-lactoglobulin and ovalbumin, with
results of Cade et al., who detected high titer of IgA
antibodies against gluten and casein and with findings of
Reichelt et al. who found in 27% of patients with autism
high levels of IgA antibodies against casein, gliadin and
gluten.
44. 44
• Specific allergic IgE antibodies against casein and beta-
lactoglobulin in persons with autism are with statistically
significant higher concentrations compared to their
brothers, sisters, fathers and mothers.
• Our results for autistic group compared to healthy
control subjects show higher concentrations of total IgE,
which is quite similar to the study of Peova S.
• For the first time in our study the level of IgE in persons
with autism has been determined (in 37% ⇑), and in
Lucarelli’s study 33% of autistic patients have high
values of total IgE.
• Patients with hyper IgE syndrome have: high levels of
IgE in serum, chronic dermatitis, recurrent
sinopulmonary tract infections, cold staphylococcal
abscesses. These symptomatology was present in our
autistic patients.
45. 45
• Serum IgE levels were highly correlative with serum IgG4
(r=0.75) in one study, but do not correlate significantly with
other IgG subclasses. In our study we found moderate
correlation between these two variables (r = 0.35; p = 0.04).
• The cytokine recombinant interleukin 4 (IL-4) enhanced not
only spontaneous IgE synthesis but also IgG4 synthesis in
cultures of lymphocytes from patients hyper IgE syndrome as
well as in healthy donors (p < 0.01).
• The disturbed regulation of IgE and IgG4 seen in patients
with hyper IgE syndrome maybe caused mainly by the
disturbed regulation of both cytokines. This effect of
recombinant IL-4 towards IgE and IgG4 was inhibited by low
concentrations of recombinant interferon-gamma.
• These our first results underline the existence of intolerance
or allergy to some food products especially casein and beta-
lactoglobulin and by that we confirm the hypothesis of
involvement of allergies and other immunological
disturbances in the etiopathogenesis of autism.
46. 46
CONCLUSIONS
• The prevalence rate of autism in Macedonia is 0.25
persons on 10.000 citizens;
• The male gender is 2.5 times more frequent then
female;
• Mean age of autistic persons is about 11 years;
• Imunogenetic analyses in autistic persons shows that
HLA-C*03 (p = 0.03) and HLA-DRB1*01 (p =
0.012) alleles are associated factors with autism;
• None of our patients carried allele or haplotype,
which were protective in our population;
47. 47
CONCLUSIONS
• Plasma concentration of IgG4 subclass immunoglobulin
is significantly higher in persons with autism (p < 0.02);
• The concentrations of IgA, IgM, total IgG, and subclasses
(IgG1, IgG2 and IgG3) are not significantly different
between autistic children and their brothers and sisters;
• Plasma concentration of immunoglobulins wasn’t
significantly different between males and females with
autism.
• Statistically significant higher plasma concentration of
IgG antibodies against alfa-lactalbumin, beta-
lactoglobulin and casein is found in autistic persons
compared to their parents (p < 0.001);
• The concentration of IgG gliadin antibodies in autistic
persons was found to be higher compared to their
mothers and fathers which is statistically significant
(p < 0.04);
48. 48
CONCLUSIONS
• Plasma concentration of specific allergic IgA antibodies
against beta-lactoglobulin in persons with autism is
significantly higher compared to brothers and sisters
(p < 0.05);
• The level of casein IgA antibodies in autistic group was
significantly higher compared with those of their
mothers and fathers (p < 0.01) and brothers/sisters
(p < 0.05);
• The level of casein and beta-lactoglobulin specific
allergic IgE antibodies in the serum of autistic patients
was significantly higher compared with those of their
brothers/sisters and their parents (p < 0.04);
• The level of total IgE antibodies was statistically
significant higher in autistic persons compared to their
mothers (p<0.04) and their brothers/sisters (p < 0.02).
49. 49
ACKNOWLEDGMENT
• Families of persons with autism;
• Institute of Special Education;
• Institute of Immunobiology and Human
Genetics;
• Ministry of Education and Science of
Macedonian Government;
• Institute of rehabilitation of hear, speech, and
voice;
• Institute of mental health;
• Special Institute Demir Kapija;