Intravenous immunoglobulin (IVIG) preparations are derived from pooled human plasma containing predominantly IgG. IVIG is used for IgG replacement therapy in immunocompromised patients at doses of 0.5 g/kg, and for suppression of autoimmune diseases at higher doses of 1-3 g/kg. IVIG has numerous proposed mechanisms of action including Fc receptor blockade, cytokine neutralization, modulation of B cell and T cell function, and inhibition of complement deposition. IVIG is administered intravenously over 2-4 hours, while subcutaneous immunoglobulin (SCIG) is infused weekly via pump at doses approximating IVIG therapy.
By Dr. Usama Ragab Youssif
Definitions & Nomenclatures
Structure of immunoglobulins
Immunoglobulins in our bodies
Physiologic actions of immunoglobulins
The Idea behind use of immunoglobulins
Uses: indications, mechanisms, preparation, posology, administration
Adverse effects
Safe practice
Final bottom-line
Intravenous Immunoglobulin (IVIG) is a solution of highly purified immunoglobulin G, derived from large pools of human plasma that contains antibodies against a broad spectrum of bacterial and viral agents.
IVIG can be given safely in the convenience of your home. It can be given either intravenously (IV through the veins) or subcutaneously (under the skin).
NBN Infusions will send a nurse with all necessary supplies to complete your infusion, in the comfort of your own home.
NBN Infusions will even help you and your doctor complete all necessary documents. Our goal is to make the process as easy as possible so you can focus on getting the treatment that you need.
Insurance companies can be challenging to deal with in the IVIG treatment approval process sometimes. So, NBN Infusions will help you deal with your insurance process so that you can get approved for your IVIG treatments in a timely manner.
What Does IVIG Treat?
IVIG Therapy has been used extensively in the treatment and prevention of a variety of infectious and inflammatory diseases. Patients with compromised Immune systems who have these conditions often benefit from the passive immunity provided by IVIG therapy.
IVIG is used in patients with primary immunodeficiencies and certain conditions associated with B-cell Chronic Lymphocytic Leukemia, Pediatric HIV, and Bone Marrow Transplant. IVIG is also utilized to raise platelet counts in patients with Idiopathic Thrombocytopenic Purpura and to treat the symptoms related to other clinical conditions such as Kawasaki Syndrome.
Various other diseases and immune disorders where IVIG is used include:
Chronic Sinusitis
Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)
Multiple Sclerosis (MS)
Myasthenia Gravis(MG)
Systenic Lupus Erythematosus (SLE)
Guillain-Barre Syndrome (GBS)
Autoimmune Diabetic Neuropathy
Polymyositis
Multifocal Motor Neuropathy (MMN)
Dermatomyositis
Rheumatoid Arthritis (RA)
Common Variable Immunodeficiency (CVID)
Hypogammaglobulinemia
Severe Combined Immunodeficiency (SCID)
Wiskott-Aldrich Syndrome (WAS)
X-Linked Agammaglobulinemia (XLA)
other connective tissue disorders
By Dr. Usama Ragab Youssif
Definitions & Nomenclatures
Structure of immunoglobulins
Immunoglobulins in our bodies
Physiologic actions of immunoglobulins
The Idea behind use of immunoglobulins
Uses: indications, mechanisms, preparation, posology, administration
Adverse effects
Safe practice
Final bottom-line
Intravenous Immunoglobulin (IVIG) is a solution of highly purified immunoglobulin G, derived from large pools of human plasma that contains antibodies against a broad spectrum of bacterial and viral agents.
IVIG can be given safely in the convenience of your home. It can be given either intravenously (IV through the veins) or subcutaneously (under the skin).
NBN Infusions will send a nurse with all necessary supplies to complete your infusion, in the comfort of your own home.
NBN Infusions will even help you and your doctor complete all necessary documents. Our goal is to make the process as easy as possible so you can focus on getting the treatment that you need.
Insurance companies can be challenging to deal with in the IVIG treatment approval process sometimes. So, NBN Infusions will help you deal with your insurance process so that you can get approved for your IVIG treatments in a timely manner.
What Does IVIG Treat?
IVIG Therapy has been used extensively in the treatment and prevention of a variety of infectious and inflammatory diseases. Patients with compromised Immune systems who have these conditions often benefit from the passive immunity provided by IVIG therapy.
IVIG is used in patients with primary immunodeficiencies and certain conditions associated with B-cell Chronic Lymphocytic Leukemia, Pediatric HIV, and Bone Marrow Transplant. IVIG is also utilized to raise platelet counts in patients with Idiopathic Thrombocytopenic Purpura and to treat the symptoms related to other clinical conditions such as Kawasaki Syndrome.
Various other diseases and immune disorders where IVIG is used include:
Chronic Sinusitis
Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)
Multiple Sclerosis (MS)
Myasthenia Gravis(MG)
Systenic Lupus Erythematosus (SLE)
Guillain-Barre Syndrome (GBS)
Autoimmune Diabetic Neuropathy
Polymyositis
Multifocal Motor Neuropathy (MMN)
Dermatomyositis
Rheumatoid Arthritis (RA)
Common Variable Immunodeficiency (CVID)
Hypogammaglobulinemia
Severe Combined Immunodeficiency (SCID)
Wiskott-Aldrich Syndrome (WAS)
X-Linked Agammaglobulinemia (XLA)
other connective tissue disorders
Immunological Disorders can be classified into 3 distinct categories.They are Hypersensitivity, Autoimmunity and Immunodeficiency.Here in this presentation we talk about Immunodeficiency disorders.Get more on our blog : http://dentistryandmedicine.blogspot.com/
This PPT encompasses the recent biologics overview & their uses in various rheumatological diseases according to recent guidelines. Special focus has been given to RA, SpA & SLE
This presentation to ensure that Intravenous Immune Globulin (IVIG) is safely administered to patients for clinically indicated conditions with a goal to optimize patient outcomes.
The rate of administration will vary according to the product prescribed. Each product has different formulations, with varying vial size and different administration instructions.
Infusion rates should be individualized to the patient’s risk factors, comorbidities and tolerability.
Graft versus host disease (GVHD) is an immune mediated disease due to complex interaction between donor (lymphoid tissue) and recipient’s immunity occurring after transplantation.
Two types
Acute (less than 100 days)
Chronic (more than 100 days)
Pediatric Home Service Medical Director, Dr. Roy Maynard discusses deficiencies of innate immune system and other well-defined immunodeficiency syndromes.
Presenation Overview:
IgG in PIDD: treatment goals
IgG trough levels and personalizing dose
IGIV vs IGSC: pros and cons today
Enzyme-facilitated IgG administration
Presentation by:
Richard L. Wasserman, MD, PhD
DallasAllergyImmunology Research
Clinical Professor of Pediatrics
University of Texas Southwestern Medical School
Medical Director of Pediatric Allergy and Immunology
Medical City Children’s Hospital
Dallas, Texas
Immunological Disorders can be classified into 3 distinct categories.They are Hypersensitivity, Autoimmunity and Immunodeficiency.Here in this presentation we talk about Immunodeficiency disorders.Get more on our blog : http://dentistryandmedicine.blogspot.com/
This PPT encompasses the recent biologics overview & their uses in various rheumatological diseases according to recent guidelines. Special focus has been given to RA, SpA & SLE
This presentation to ensure that Intravenous Immune Globulin (IVIG) is safely administered to patients for clinically indicated conditions with a goal to optimize patient outcomes.
The rate of administration will vary according to the product prescribed. Each product has different formulations, with varying vial size and different administration instructions.
Infusion rates should be individualized to the patient’s risk factors, comorbidities and tolerability.
Graft versus host disease (GVHD) is an immune mediated disease due to complex interaction between donor (lymphoid tissue) and recipient’s immunity occurring after transplantation.
Two types
Acute (less than 100 days)
Chronic (more than 100 days)
Pediatric Home Service Medical Director, Dr. Roy Maynard discusses deficiencies of innate immune system and other well-defined immunodeficiency syndromes.
Presenation Overview:
IgG in PIDD: treatment goals
IgG trough levels and personalizing dose
IGIV vs IGSC: pros and cons today
Enzyme-facilitated IgG administration
Presentation by:
Richard L. Wasserman, MD, PhD
DallasAllergyImmunology Research
Clinical Professor of Pediatrics
University of Texas Southwestern Medical School
Medical Director of Pediatric Allergy and Immunology
Medical City Children’s Hospital
Dallas, Texas
Immunosupressants and Immunostimulants their pharmacology, uses etc. Basics of immunology, innate immune response, acquired immune response, role of complement in innate immune response. Major histocompatibility complex, antibody structure. classification of immunosupressants, their mechanism of action, uses and adverse effects.
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Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
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The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
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2 Case Reports of Gastric Ultrasound
These lecture slides, by Dr Sidra Arshad, offer a quick overview of 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 leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
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. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
1. Immunoglobulin Therapy
Puttatida Chetwong, MD.
10 September 2021
Division of Pediatric Allergy Immunology and Rheumatology
Department of Pediatrics, Faculty of Medicine
King Chulalongkorn Memorial Hospital
2. •Intravenous immunoglobulin (IVIG) preparations comprise the pooled
fraction of serum IgG from ~3,000–60,000 blood donors
•Generated in principle by a cold ethanol precipitation.
•Besides IgG, varying amounts of other immunoglobulin isotypes, most
notably IgA, can be found in the IVIG preparation.
•The clinical use of IVIG can be distinguished by the infused amount.
• For IgG replacement therapy to prevent microbial infections in
immunocompromised patients, doses of approximately 0.5 g per kg body weight
are used.
• For the suppression of autoimmune diseases, IVIG is infused at much higher
doses, which range from 1–3 g per kg body weight.
Nat Rev Immunol. 2013 Mar;13(3):176-89.
Overview of IVIG
8. Fc receptor expression patterns on human cells and biologic activity
Middleton’s allergy: principles and practice. 9th ed.
9. Middleton’s allergy: principles and practice. 9th ed.
Neonatal Fc receptor for IgG (FcRn)
• Endothelial cells and monocytes express the
neonatal Fc receptor for IgG (FcRn) that
internalizes serum IgG in an acidic
endosomal compartment.
• FcRn then recycles IgG molecules back into
circulation, effectively prolonging their half-life.
• Serum proteins without a recycling receptor
are internalized in lysosomes and degraded.
14. J Allergy Clin Immunol. 2011 Feb;127(2):315-23
• Benefit in ITP
• Fc receptor blockade of the reticuloendothelial system platelet counts
rapidly increase after administration of IVIG (dose 1-2 g/kg)
• Autoantibody-opsonized platelets are destroyed in spleen and liver by
means of FcᵧR-mediated phagocytic clearance.
• Fc receptor blockade on macrophages in spleen and in other parts of
the reticuloendothelial system using an mAb directed against the
FcᵧRIIIa receptor
Fc receptor blockade
15. J Allergy Clin Immunol. 2011 Feb;127(2):315-23
Benefit in
• circulating autoantibody inhibitors to Factor VIII coagulant activity
• SLE
• Anti-neutrophil cytoplasmic antibody-associated vasculitis
• Guillain-Barre syndrome (GBS)
• Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)
• Myasthenia gravis
Restoration of the idiotypic–anti-idiotypic
network
16. J Allergy Clin Immunol. 2011 Feb;127(2):315-23
• IVIG demonstrated that low levels of autoreactive IgG antibodies that
recognize a wide array of self antigens
Self antigens:
• Cytokines
• Antigen-specific autoantibody
• CD95 (also known as FAS) or CD95 ligand (FASL)
• Sialic acid-binding immunoglobulin-like lectin 9 (SIGLEC9) expressed on
neutrophils
• SIGLEC8 expressed on eosinophils
• T cell-expressed antigens
• B cell-activating factor (BAFF), A proliferation-inducing ligand (APRIL)
• Adhesion molecules involved in leukocyte trafficking
Cytokine, autoantibody
neutralization
17. J Allergy Clin Immunol. 2011 Feb;127(2):315-23
• Benefit in Kawasaki disease
• IVIG preparations contain neutralizing antibodies to staphylococcal derived enterotoxins
• Inhibit T-cell activation by these staphylococcal and streptococcal superantigens
• Inhibits production of cytokines by mononuclear cells (IL-1, TNF-a, TNF-b, and IFN-g by
PBMCs)
• Increasing production of IL-1 receptor antagonist
• Inhibits endothelial cell proliferation
• Downregulates mRNA expression of adhesion molecule (ICAM1, VCAM1), chemokine
Suppression of cytokine
production
18. J Allergy Clin Immunol. 2011 Feb;127(2):315-23
• Benefit in Dermatomyositis, GBS, CIDP, Myasthenia gravis
• In vitro study: high levels of IgG could inhibit the uptake of C3 on
erythrocytes and inhibition of binding of C3b to antibodies on platelets
reduce C3b dependent opsonization of antibody-coated platelets by
macrophages of the RE system
• Decrease C3 and MAC deposition on endomysial capillaries and
decrease ICAM1 expression in muscle tissue
• Prevent complement mediated neuronal cell death
Inhibition of complement deposition on target
tissue
19. J Allergy Clin Immunol. 2011 Feb;127(2):315-23
• TEN: death of the keratinocytes leads to large sections of the epidermis sloughing off
• Keratinocytes express Fas, and sera contain high circulating levels of Fas ligand
• IVIG contains anti-Fas antibodies prevent keratinocyte cell death by blocking the effects
of Fas ligand on Fas receptor on keratinocytes
• The anti-Fas antibodies in IVIG can enhance the apoptosis of human lymphocytes and
monocytes.
• Immunomodulating effects of anti-Fas antibodies might depend on the dose of IVIG and
the clinical disease state
• Low conc. (1-10 mg/mL) blocked anti-CD95–mediated neutrophil apoptosis
• High conc. (20-50 mg/mL) induced neutrophil death
Modulation of apoptosis
20. J Allergy Clin Immunol. 2011 Feb;127(2):315-23
• Long term effects in ITP
• inhibited both B cell receptor–dependent and independent antigen presentation
(not mediated through the FcᵧRIIb receptor but was mediated by intracellular
events)
• Under specific conditions such as CD40 activation: IVIG promote differentiation
into IgG secreting B cells
• Contains other specific antibodies that react with number of cell-surface
determinants that could potentially modulate the immune response, such as the
αβ TCR, cytokine receptors, HLA determinants, CD5, CCR5, CD40, and sialic
acid–binding immunoglobulin-like lectins 8 and 9.
Modulation of B cells
21. J Allergy Clin Immunol. 2011 Feb;127(2):315-23
• Benefit in Bullous pemphigoid, Arthritis, ITP
• FcRn: specialized receptor binds serum IgG,
protects IgG from degradation inside the lysosomes,
and returns IgG intact to plasma circulation
• Shorten the half-life of the autoantibody, more
rapidly eliminating it from the circulation
Saturation of FcRn
22. J Allergy Clin Immunol. 2011 Feb;127(2):315-23
• Benefit in ITP, Rheumatoid arthritis, nephrotoxic
nephritis, chronic inflammatory demyelinating
polyneuropathy
• IVIG stimulates inhibitory FcᵧRIIb receptors
• IVIG enriched for sialylated glycan moiety
inhibitory or anti-inflammatory properties
Modulation of immunoregulatory function
through the Fc receptor
N Engl J Med. 2012 Nov 22;367(21):2015-25.
23. J Allergy Clin Immunol. 2011 Feb;127(2):315-23
• Benefit in Kawasaki disease, GBS, autoimmune encephalomyelitis
• Suppress T-cell proliferative responses to mitogens by IVIG and
F(ab’)2 fragments to CD3 and CD28 stimulations
• Expanding and enhancing the function of FOXP3-positive Treg cells
increase production of IL-10, TGF-β, or effects on DC cells
• Inhibited maturation of monocytes into immature dendritic cells
Modulation of T cell immunoregulatory
function
34. Dose is absorbed slowly and redistributed
slowly, whereas concentration dependent
catabolism is ongoing
Serum IgG levels during SCIG therapy
(A) Weekly infusions. The IgG levels vary, on
average, less than 10% over the week in between
infusions.
(B) Biweekly infusions. The IgG level varies more
than it does with weekly infusions, but not as
much as with IVIG. The absorption is still blunted
in comparison to IVIG.
Immunol Allergy Clin North Am. 2008 Nov;28(4):803-19
39. • The usual recommended dose of IGIV for immunodeficiency is 300 to 500 mg/kg given
every 3 to 4 weeks.
• The usual initial rate of infusion is 0.01 mL/kg/minute, which provides 0.5 or 1
mg/kg/minute of IgG depending whether a 5% or a 10% IGIV is used, respectively.
• The infusion rate can be doubled every 20 to 30 minutes until a rate of 0.08 mL/kg is
achieved.
• The infusion usually takes 2 to 4 hours.
• This may be longer if higher doses are given or shorter if the patient has tolerated a
more rapid rate or shorter interval between doses.
IVIG Dose
Transfus Med Rev. 2013 Jul;27(3):171-8.
40. • Higher doses of IGIV are used for autoimmune and inflammatory diseases, typically 1 to
2 g/kg per dose, and repeated at regular intervals.
• The daily dose of no more than 1 g/kg/day be given to most patients under age 60
and no more than 500 mg/kg/ day be given to patients over age 60 or to high risk patients.
• Patients requiring higher doses can get 500 mg/kg on subsequent days.
• The maximal dose is usually based on a weight of 70 kg, regardless of the patient’s
actual weight.
IVIG Dose
Transfus Med Rev. 2013 Jul;27(3):171-8.
41. • The usual dose for SCIG is also 300 to 500 mg/kg/month, similar to the IGIV dose.
• Infusions are usually given weekly at 25% of the monthly dose.
• Thus a weekly dose of 100 mg/kg (400 mg/kg/month requires a subcutaneous infusion of
1.0 mL/kg of a 10% IG product or 0.5 mL/kg of a 20% IG product.)
• This is usually given slowly using a portable infusion pump.
• Multiple sites on the abdominal wall, thighs or arms can be used so that no more than 5
to 30 mL is given at a single site, depending on the patient’s weight.
• Because of the lessened risk of systemic side effects, SCIG can be given at home,
often by self-infusion, and without premedication
SCIG Dose
Transfus Med Rev. 2013 Jul;27(3):171-8.
58. Volume load
• an important consideration in very young, elderly, cardiac impairment
Sodium content
• Varies widely in currently available preparations
• High salt contents higher incidence of AEs & thromboembolic complications
Osmolality
• Sodium & sugar content
• Physiologic osmolality: 280-296 mOsm/kg of water
• Hyperosmotic state thromboembolic complications
pH
• Optimum pH: 4.0-4.5 to remain IgG in unaggregated state
• Low pH may be associated with phlebitis
Int Immunopharmacol. 2006 Apr;6(4):592-9.
59. IgA Content
• IgG or IgE anti-IgA antibodies in patients with hypogammaglobulinemia
and absent serum IgA who are receiving IgA-containing IVIG can cause
severe reactions including anaphylaxis.
– CVID patient with serum IgA level <7 mg/dL are at highest risk.
• To minimize risk of severe reactions/anaphylaxis
– Use products with the lowest concentration of IgA
– Starting initial IVIG infusion slowly and gradually increase the
rate with subsequent infusions
Immunol Allergy Clin North Am. 2015;35(4):713-30.
60.
61. Amount (gram) Volume (ml) ราคาขาย
5% LIV-Gamma 5 g 100 7,211
5% Flebogamma DIF 2.5 g 50 6,111
5% Flebogamma DIF 10 g 200 24,261
5% TRCS 2.5 g 50 2,790
5% TRCS 5 g 100 5,150
10% Kiovig 5 g 50 12,125
10% Kiovig 10 g 100 22,983
10% Gamunex-C 2.5 g 25 5,822
10% Gamunex-C 10 g 100 22,071
10% Privigen 5 g 50 11,501
20% Huzentra 4 g 20 14,821
66. • 40-year-old female presenting with productive cough, fatigue, and postnasal drip for 3 days
• History:
- Repetitive sinusitis, otitis media, diarrhea, cystitis, and pneumonia since childhood
- Concomitant conditions: hypertension (155/90 mmHg),
pre-diabetes (fasting glucose: 120 mg/dL)
• Lab values:
- IgG 100 mg/dL (620-1400 mg/dL)
- IgA 30 mg/dL (80-350 mg/dL)
- IgM 25 mg/dL (45-250 mg/dL)
• Diagnosis: common variable immune deficiency
What to consider in this patient?
Editor's Notes
F(ab′)2- and Fc-dependent pathways of IVIG activity. Shown is an overview of the different pathwaysthat have been implicated in intravenous immunoglobulin (IVIG)-mediated immunomodulation. F(ab′)2-dependentmechanisms include: the killing of target cells by antibody-dependent cytotoxicity (ADCC); the blockade of cell–cellinteractions mediated by cell-surface receptors, such as CD95 and CD95 ligand (CD95L); the neutralization of cytokines;the neutralization of autoantibodies by anti-idiotypic antibodies; and the scavenging of the anaphylatoxins C3a andC5a. Fc-dependent pathways include: the saturation of the neonatal Fc receptor (FcRn); the expansion of regulatory T(TReg) cell populations; the blockade of immune complex binding to low-affinity Fcγ receptors (FcγRs); the modulation ofdendritic cell activation via FcγRIII; and the modulation of activating and inhibitory FcγR expression on innate immuneeffector cells and B cells.
A schematic representation of the proposed mechanisms of action of intravenous immunoglobulin in rheumatic diseases.The mechanisms that underlie the beneficial effects of IVIg involve its direct interaction with various cellular and soluble componentsof the immune system. IVIg stimulates the expression of FcγRIIB on a subset of macrophages while blocking the expression ofFcγRIIA (A). IVIg also modulates cytokine secretion, blocks the expression of Fc receptors and inhibits the activation of macrophages(A) and dendritic cells (B). In addition to inhibition of the activation and production of proinflammatory cytokines by T cells (C), IVIgdownregulates DC-mediated T-cell proliferation. At the B-cell level (D), IVIg modulates antibody synthesis and the B-cell repertoire,inhibits B-cell proliferation and induces B-cell-apoptosis. In endothelial cells (E) IVIg blocks the expression of proinflammatory cytokines,chemokines and adhesion molecules. Several other mechanisms of action of IVIg exist: interference with complement activation (F);neutralization of superantigens (G), pathogenic autoantibodies (H) and cytokines (I); sequestration of self antigens (J); induction ofADCC (K) and shifting the balance between T-helper cell subsets (L). The area encompassed by endothelial cells represents the vascularlumen. Adhesion molecules on endothelial cells are depicted. IVIg is depicted in the form of antibody structures with different colors tohighlight the fact that it is a polyclonal IgG obtained from pooled plasma from a large number of healthy blood donors. Soluble factorssuch as complement proteins and cytokines are indicated by colored circles. Abbreviations: ADCC, antibody-dependent cell-mediatedcytotoxicity; B, B cell; DC, dendritic cell; EC, endothelial cell; FcγR, Fcγ receptors; NK, natural killer cell; T, T cell.
Two-compartment model of IgG pharmacokinetics. (A) IgG is in equilibrium betweenthe vascular space and extravascular areas. IgG is synthesized in the bone marrow anddiffuses into the lymph and then to the blood. SCIG is absorbed from subcutaneous tissues.IVIG enters the vascular space directly. IgG is catabolized in vascular endothelium (and pos-sibly other areas). IgG also may be lost from the vascular space by various mechanisms(eg, protein loss in the intestines or urinary tract). (B) Serum IgG concentration over timeduring IVIG replacement therapy. With IV administration, IgG enters the vascular compart-ment in high concentration, redistributes rapidly into tissue compartments, and then ismore slowly catabolized. The early redistribution phase is sometimes called the aphase,and the later slow decline is the bphase
• Liquid:– “ready-to-use” preparations– 5% solution (5 gm/100 mL)– 10% solution (5 gm/50mL)• Lyophilized:– Reconstitute to concentrations 3-12% with water, D5W, or saline diluent– Shaking to get a product into solution may be associated with some proteindenaturation– Hyperosmolar solutions are easily created when reconstituted with lower thanrecommended diluent volumes
J Allergy Clin Immunol Pract 2013;1:558-66.
Volume load• an important consideration in very young, elderly, cardiac impairmentSodium content• Varies widely in currently available preparations• High salt contents à higher incidence of AEs & thromboembolic complicationsOsmolality• Sodium & sugar content• Physiologic osmolality: 280-296 mOsm/kg of water• Hyperosmotic state à thromboembolic complicationspH• Optimum pH: 4.0-4.5 to remain IgG in unaggregated state• Low pH may be associated with phlebitis