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
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
chronic myeloid leukemia, CML, epidemiology, BCR ABL1 gene, philadelphia chromosome, t(9;22), CML incidence, etiology of CML, pathophysiology of CML, phases of CML, treatment of CML, Allogenic stem cell transplant, TKI therapy for CML, Sokal index for CML,
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)
chronic myeloid leukemia, CML, epidemiology, BCR ABL1 gene, philadelphia chromosome, t(9;22), CML incidence, etiology of CML, pathophysiology of CML, phases of CML, treatment of CML, Allogenic stem cell transplant, TKI therapy for CML, Sokal index for CML,
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)
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
We investigated the the probiotic strains Lactobacillus rhamnosus, Lactobacillus reuteri, Bifidobacterium longum infantis and Lactobacillus helveticus for their ability to modulate cytokine release in primary murine mast cells in vitro
West African Sorghum Extract Again Shows Immune Health Benefits : Health-foreverHealth Forever
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Controversy: the role of immunomodulator in allergic caseSuharti Wairagya
dipresentasikan oleh Erwanto BW Teguh HK
Divisi Alergi Imunologi Klinik Departemen 1. Penyakit Dalam FKUI/RSCM Bagian Penyakit Dalam SMF non Bedah RS. dr. H. Marzoeki Mahdi Bogor
Safety and efficacy of IgM-enriched intravenous immunoglobulins as adjunctive...Sanja Sakan
Safety and efficacy of IgM-enriched intravenous immunoglobulins as adjunctive therapy in patients with sepsis-review of literature
Sanja Sakan1, Jasminka Persec1,2, Dinko Milavec1, Daniela Bandic Pavlovic3,4
1Clinical department of anesthesia and intensive medicine, University Hospital Dubrava, Zagreb, Croatia
2 School of dental medicine, University of Zagreb, Zagreb, Croatia
3Clinical department of anesthesia and intensive care, Clinical Hospital Center Zagreb, Zagreb,Croatia
4School of medicine, University of Zagreb, Zagreb, Croatia
Correspondence to: Sanja Sakan, PhD, Clinical department of anesthesiology and intensive medicine, University hospital Dubrava ,Zagreb, Croatia
e-mail: sanja.sakan@hotmail.com
Abstract
Treatment of sepsis still represents a big medical challenge and a great burden for the cost of healthcare system. Immunomodulatory therapy with IgM-enriched intravenous immunoglobulis could be a novel effective adjunctive therapy to 24-hrs surviving sepsis bundels. However there are not so many large homogenous clinical studies to justify cost-benefit of the IgM-enriched immunoglobulins use and the right timing for their application. For now the results of the present clinical studies are controversial.
Keywords: IgM-enriched IVIG, pentaglobin, sepsis, septic shock
Similar to Intravenous immunoglobulin therapy (IVIG) (20)
Diabetic Peripheral Neuropathy and Vitamin B12 IssueUsama Ragab
Diabetic Peripheral Neuropathy and Vitamin B12 Issue
By Dr. Usama Ragab Youssif
Diabetic neuropathies are the most prevalent chronic complications of diabetes
Central and Peripheral Precocious PubertyUsama Ragab
Precocious Puberty
By Dr. Usama Ragab Youssif
Precocious puberty (PP) is defined as the development of pubertal changes (2ry sexual characters), at an age younger than the accepted lower limits for age of onset of puberty.
Algorithms for Diabetes Management for StudentsUsama Ragab
Algorithms for Diabetes Management for Students
By Usama Ragab Youssif
Lecturer of Medicine - Zagazig University
Agenda
Type 2 Diabetes 101
Incretin based therapy
Algorithms of management
Email: usamaragab@medicine.zu.edu.eg, usama.ragab.zu@gmail.com
SlideShare: https://www.slideshare.net/dr4spring/
Facebook: https://www.facebook.com/doc.usama
Facebook Clinic: https://www.facebook.com/usamaclinic
Mobile: 00201000035863
Classification & Diagnosis of Diabetes.pptx
By Dr. Usama Ragab Youssif
Lecturer of Internal Medicine Zagazig University
Email: usamaragab@medicine.zu.edu.eg, usama.ragab.zu@gmail.com
SlideShare: https://www.slideshare.net/dr4spring/
Facebook: https://www.facebook.com/doc.usama
Facebook Clinic: https://www.facebook.com/usamaclinic
Mobile: 00201000035863
Renal System - History Taking
By Dr. Usama Ragab Youssif
Lecturer of Medicine, Zagazig University
Email: usamaragab@medicine.zu.edu.eg, usama.ragab.zu@gmail.com
SlideShare: https://www.slideshare.net/dr4spring/
Facebook: https://www.facebook.com/doc.usama
Facebook Clinic: https://www.facebook.com/usamaclinic
Mobile: 00201000035863
Clinical Endocrinology Round
By Dr. Usama Ragab Youssif
Lecturer of Medicine
Zagazig University
Acromegaly
Cushing
Diabetes
Thyroid
Addison
Techniques and clinical insights
Functional Bowel Disorders
By Dr. Usama Ragab
Esophageal Disorders
Gastroduodenal Disorders
Bowel disorders
Centrally Mediated Disorders of GI Pain
Gallbladder and Sphincter of Oddi Disorders
Anorectal disorders
Childhood Functional GI Disorders: Neonate/Toddler
Childhood Functional GI Disorders: Child/Adolescent
Heat, Cold and High Altitude Related illnessUsama Ragab
Heat, Cold and High Altitude Related illness
By Dr Usama Ragab
Lecturer of Medicine
Topics are heat and cold related illness and high altitude medical disorders
Imeglimin, What is new?
By Dr. Usama Ragab Youssif
Lecturer of Medicine - Zagazig University
Agenda
Mitochondrial function and dysfunction
Mitochondrial (dys)function in diabetes
Diabetes core defects and Imeglimin
Imeglimin drug development and approval
Imeglimin and Heart
Diabetes and Gut interplay
By Dr. Usama Ragab Youssif
In Gastro Canal Association Annual Conference
Agenda
Diabetes as the main player
Gut as the main player
Diabetes and gut in a separate game
Gut as game changer
Tips and tricks: diabetes drugs
Guidelines in Obesity management
By Dr. Usama Ragab Youssif
Obesity-related counseling should be offered to those with BMI ≥25 kg/m2
A 3% to 5% weight loss can result in meaningful reductions in triglycerides, blood glucose, hemoglobin A1c, and the risk of developing type 2 diabetes
Set an initial weight loss goal of 5% to 10% of current body weight over 6 mo
After 6 mo, focus on weight maintenance before attempting further weight loss
Participating in a weight loss program long-term can help improve weight maintenance
Intensification Options after basal Insulin RevisitedUsama Ragab
Intensification Options revisited
By Dr. Usama Ragab Youssif
Add an OAD
Add a short-acting insulin at mealtime
Switch to premixed insulins
Novel insulin combinations
Basal insulin/GLP-1 RA combinations
Insulin Lispro Revisited
By Dr. Usama Ragab Youssif
The discovery of insulin was one of the most dramatic and important milestones in medicine - a Nobel Prize-winning moment in science.
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
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
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
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
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?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
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micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
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Hemodialysis: Chapter 3, Dialysis Water Unit - Dr.Gawad
Intravenous immunoglobulin therapy (IVIG)
1. Usama Ragab Youssif
Assistant Lecturer Of Medicine
Clinical Immunology
IVIG
Sunday, 6 January 2019
Sharkia Medical Syndicate
Clinical Immunology 1st Announcement
2. Outlines
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
2
3. Immunoglobulins
Also called antibodies.
Group of glycoprotiens present in the serum and
tissue fluid of all mammals.
They are found mainly in the gamma globulin
fraction of the serum.
They bind specifically to the antigen that induced
their production.
Produced by differentiated B cells termed plasma
cells
3
Abla M. El-Mishad: Manual of Microbiology & Immunology. Vol I 8th Edition. 2010 El-Ahram press Egypt
4. IVIG or IVIg
IVIG is an abbreviation for Intravenous
Immunoglobulin
Administered intravenously in case of IVIG
IG therapy has other route.
4
Spickett, Gavin. Oxford handbook of clinical immunology and allergy. Oxford University Press, 2013.
6. Structure of immunoglobulin (cont.)
6
Gorczynski, R., and J. Stanley. "Clinical immunology–An introductory text." Immunology, T lympho-cytes. Texas: Landes Bioscience (1999): 2-185.
7. Structure of immunoglobulin (cont.)
Diversity
Specificity
Cellular
Biologic
7
Gorczynski, R., and J. Stanley. "Clinical immunology–An introductory text." Immunology, T lympho-cytes. Texas: Landes Bioscience (1999): 2-185.
8. Structure of immunoglobulin (cont.)
8
Gorczynski, R., and J. Stanley. "Clinical immunology–An introductory text." Immunology, T lympho-cytes. Texas: Landes Bioscience (1999): 2-185.
9. Physiologic Effects of IgG
Fab fragment activity = antigen binding site
Agglutination
Neutralization
Opsonization
9
Abla M. El-Mishad: Manual of Microbiology & Immunology. Vol I 8th Edition. 2010 El-Ahram press Egypt
10. Physiologic Effects of IgG (cont.)
Fc fragment activity = Crystallization Fragment
Complement
activation ADCC
Inflammation
10
Abla M. El-Mishad: Manual of Microbiology & Immunology. Vol I 8th Edition. 2010 El-Ahram press Egypt
11. How B-cell produces Igs
• Initial signal= Ag-Ab on surface of B-cell after
leaving BM to be processed and presented in
association with MHC-II to T-cell (TCR)
• Co-stimulatory signals=
- B7 on B-cell with CD28 on T-cell.
- CD40 to be associated with CD40L on T-cell.
• Cytokine release: IL-2,4,5,6
• Memory cell production
11
Abla M. El-Mishad: Manual of Microbiology & Immunology. Vol I 8th Edition. 2010 El-Ahram press Egypt
12. How B-cell produces Igs (cont.)
12
CD40/CD40L
Abla M. El-Mishad: Manual of Microbiology & Immunology. Vol I 8th Edition. 2010 El-Ahram press Egypt
13. How B-cell produces Igs (cont.)
13
Abla M. El-Mishad: Manual of Microbiology & Immunology. Vol I 8th Edition. 2010 El-Ahram press Egypt
14. Uses of IVIG
• Replacement therapy.
• Immunomodulatory effect.
14
Jessica Katz, and Kinjal Parikh. "Intravenous immunoglobulin." Medscape (2018).
16. Mechansim of IVIG as Replacement
16
Peter, J. G., J. M. Heckmann, and N. Novitzky. "Recommendations for the use of immunoglobulin therapy for immunomodulation and antibody
replacement." South African Medical Journal 104.11 (2014): 796.
17. Mechansim of IVIG as Immunomodulatory
17
Gelfand, Erwin W. "Intravenous immune globulin in autoimmune and inflammatory diseases." New England Journal of Medicine 367.21
(2012): 2015-2025.
18. Example for IVIG role in ITP
• Fc receptor blockade of reticuloendothelial system
• Fcγ receptor downregulation
• Idiotype–antiidiotype interaction between
antiplatelet GPIIb/IIa autoantibodies and the
antiidiotypic antibodies in IVIG
• Activation of inhibitory receptor FcγRIIB
• Saturation of FcRn receptor to accelerate the
catabolism of antiplatelet autoantibodies
19
Abla M. El-Mishad: Manual of Microbiology & Immunology. Vol I 8th Edition. 2010 El-Ahram press Egypt
19. Preparation of IVIG
20
Rich, Robert R., et al. Clinical Immunology, Principles and Practice (Expert Consult-Online and Print), 5: Clinical Immunology. Elsevier Health
Sciences, 2019.
20. Preparation of IVIG (cont.)
21
Rich, Robert R., et al. Clinical Immunology, Principles and Practice (Expert Consult-Online and Print), 5: Clinical Immunology. Elsevier Health
Sciences, 2019.
It contains pooled Ig (mainly IgG)
Donor pool usually >1000 donors to ensure broad
spectrum of antibody specificities (esp. as
replacement therapy)
IVIg/SCIg is stabilized with sugars (e.g. maltose)
21. Forms available
22
Dosage Forms & Strengths
injectable solution
10% (100mg/mL)
5% (50mg/mL)
https://reference.medscape.com/drug/gammagard-s-d-carimune-nf-immune-globulin-iv-igiv-343138
22. Routes of adminstration
• IV; IVIG: the main route of treatment inpatient,
and if patient refuse inhome treatment via oter
routes. (5-10% preparations)
• IM: rarely used nowadays, doses are too low to be
effective in preventing infection. Preferred by elderly
patients who was initiated on this old fashioned
route
• SC; SCIG: For those with poor venous access, high-
dose SCIg replacement is at least equivalent to IVIg
in terms of maintaining adequate trough IgG levels
and preventing infection (16-20% preparations)
23
Spickett, Gavin. Oxford handbook of clinical immunology and allergy. Oxford University Press, 2013.
23. Routes of administration (cont.)
IVIG SCIG
Advantages •Achieve rapid plasma levels
•Can use this route in patients
with bleeding disorders
•3–4 week intervals
•IV access not needed
•Achieve stable serum levels
•Less systemic AE
•More flexibilty for parents and
patients
Disadvantages •Need IV access
•Interrupt patient’s schedule for
3–5-hour period
•Often needs to come to a
hospital or infusion center
•System side effects may be more
frequent in some patients
•Minor local reactions at the site of
infusion
•Patient reliability
•Need for a pump
24
Rich, Robert R., et al. Clinical Immunology, Principles and Practice (Expert Consult-Online and Print), 5: Clinical Immunology. Elsevier Health
Sciences, 2019.
24. Home therapy
Criteria for home therapy Comment
4-6 month of hospital treatment Must be reaction free
Good venous access for IVIg Consider SCIg if venous access poor
Patient must be motivated
Patient must have a trainable
long-term partner
Never infuse while patient alone
Hotline with treating physician or
hospital
Regular follow up Patient must agree to keep infusion
logs with batch records
25
Spickett, Gavin. Oxford handbook of clinical immunology and allergy. Oxford University Press, 2013.
25. Example for IVIG posology in different scenarios
Primary Immunodeficiency Syndrome:
- 300-600 mg/kg q3-4Week
- Initial infusion rate: 0.5 mg/kg/min for the first 30 min
Immune Thrombocytopenic Purpura
- 1 g/kg IV x 2 days or 400 mg/kg IV x 5 days
Chronic Inflammatory Demyelinating Polyneuropathy
(CIDP)
- Load: 2 g/kg IV in divided doses for 2-4 days
- Maintenance: 1000 mg/kg/day IV for 1 day q3Week or 500
mg/kg/day for 2 days q3Week
Bone Marrow Transplant
- 500 mg/kg IV beginning on days 7 & 2 pretransplantation,
THEN qWk through 90 days post-transplantation
Guillain-Barre; LEMS; Stiff Person Syndrome (Off-label):
- 400 mg/kg IV qDay x5 days or 1 g/kg qDay x 2 days
26
https://reference.medscape.com/drug/gammagard-s-d-carimune-nf-immune-globulin-iv-igiv-343138
26. IVIG adverse effects
27
Peter, J. G., J. M. Heckmann, and N. Novitzky. "Recommendations for the use of immunoglobulin therapy for immunomodulation and antibody
replacement." South African Medical Journal 104.11 (2014): 796.
27. Risk Factors for Adverse Events
• Infusion issues
1. Prior history of an infusion reaction with an
immunoglobulin (Ig) product
2. First infusion in a patient with active infection or
inflammation
3. Changing immunoglobulin products
4. Rapid infusion and/or large dose
28
Rich, Robert R., et al. Clinical Immunology, Principles and Practice (Expert Consult-Online and Print), 5: Clinical Immunology. Elsevier Health
Sciences, 2019.
28. Risk Factors for Adverse Events (cont)
• Patient factors
1. Preexisting renal impairment
2. Prior history of thrombotic event
3. Autoimmune disorder
4. Diabetes mellitus
5. Age—older age
6. Dyslipidemia
7. Dehydration with volume depletion
8. Hypercoagulable state
9. Indwelling catheters
10. Paraproteinemia or other causes of hyperviscosity
11. Cardiac or peripheral vascular disorders
12. Estrogen use
13. Smoking
29
Rich, Robert R., et al. Clinical Immunology, Principles and Practice (Expert Consult-Online and Print), 5: Clinical Immunology. Elsevier Health
Sciences, 2019.
29. Black Box Warnings
Acute renal dysfunction and renal failure
Related to sucrose content
Highly osmotic load
Associated with renal dysfunction, acute renal
failure, osmotic nephrosis, and death
Slow initial rates of infusion in high risk
patients.
Thrombosis:
May relate to underlying condition,
hyperviscosity, poor fluid balance.
30
https://reference.medscape.com/drug/gammagard-s-d-carimune-nf-immune-globulin-iv-igiv-343138
30. Contraindications
Hypersensitivity to gamma globulin
Isolated IgA deficiency
Hyperprolinemia (with some brands e.g. Privigen)
31
https://reference.medscape.com/drug/gammagard-s-d-carimune-nf-immune-globulin-iv-igiv-343138
31. Other cautions
Prion transmitted disease.
Serum sickness like reaction.
Aseptic meningitis syndrome.
Hemolytic anemia can develop subsequent to IGIV
therapy due to enhanced RBC sequestration.
Postpone live virus vaccines for at least 3 months
False high blood glucose due to high maltose content
Various passively transferred antibodies in
immunoglobulin preparations may lead to
misinterpretation of the results of serological testing
32
https://reference.medscape.com/drug/gammagard-s-d-carimune-nf-immune-globulin-iv-igiv-343138
32. Pregnancy & Lactation
Pregnancy Category: C
Use with caution if benefits outweigh risks.
Animal studies show risk and human studies
not available or neither animal nor human
studies done.
Lactation: not known if excreted in breast milk
33
https://reference.medscape.com/drug/gammagard-s-d-carimune-nf-immune-globulin-iv-igiv-343138
33. IVIG good practice points
• At initiation of therapy:
1. Check baseline renal and liver function, full blood count, and
infection screen for hepatitis B/C and HIV
2. Anticipate potential side-effects
3. Store sample of serum for later testing if any questions about
infectious agent transmission is raised
4. Consider the planned duration of therapy and product
availability to avoid unnecessary future product changes
5. Complete documentation
6. Record brand, lot number, dose and reactions with each set
7. Adequate pre-hydration; slow first infusion, incremental
increase
34
Peter, J. G., J. M. Heckmann, and N. Novitzky. "Recommendations for the use of immunoglobulin therapy for immunomodulation and antibody
replacement." South African Medical Journal 104.11 (2014): 796.
34. IVIG good practice points (cont.)
• For long-term treatment:
1. Plan further treatment routes IVIG to SCIG.
2. Review every 2 months then 6 monthly for AE,
trough levels, infection rebound if used as
replacement therapy.
3. Backup plan for uneventful travelling, pregnancy,
insurance interruption.
35
Peter, J. G., J. M. Heckmann, and N. Novitzky. "Recommendations for the use of immunoglobulin therapy for immunomodulation and antibody
replacement." South African Medical Journal 104.11 (2014): 796.
35. IVIG good practice points (cont.)
Technical issues during preparation:
Dilution is dependent upon manufacturer &
brand; do not shake, avoid foaming; discard
unused portion
Administer in separate infusion line from other
medications; flush line with NS.
Prepare epinephrine; keep it near you.
Start low go slow
First thing to do if reaction occurs, stop infusion
36
Spickett, Gavin. Oxford handbook of clinical immunology and allergy. Oxford University Press, 2013.
36. Final Bottom-line
Igs has diverse immunologic actions.
IVIG therapy has been the last resort in many
autoimmune diseases.
IVIG replacement therapy is life saving in many
immunodeficiency disorders.
There are other route for IG therapy, however in
replacement therapy only.
IVIG has many side effects, though it can be avoided
by proper selection of patients, and to expect them
when risk factors apply.
37
Editor's Notes
Light chain: variable and constant, the constant portion is either kappa or lambda.
Heavy chain: variable and constant, the constant is either γ, α, μ, ε, δ corresponding to IgG, IgA, IgM, IgE and IgD.
-----------------------
Regions that differ extensively are termed hypervariable and represent amino acid sequences that are unique to a particular antibody and complementary to a particular antigenic epitope. Hence hypervariable regions are also termed complementary determining regions, CDRs.Hypervariable regions can also serve as antigenic determinants (idiotopes). The collection of idiotopes in a given antibody defines the idiotype. Consequently, antibodies generated to the collection of idiotopes on a single antibody molecule are termed anti-idiotypic antibodies.
------------------------------------
What is an Anti-idiotypic antibody?
When one antibody binds to an idiotope of another antibody it is referred to as an anti-idiotypic antibody. The variable part of an antibody including the unique antigen binding site is known as the idiotype. The combination of epitopes within the idiotype (i.e. the idiotopes) is unique for each antibody, figure 1.
Because most therapeutic monoclonal antibodies developed today are human or humanized, the most likely immunogenic epitopes for the induction of anti-drug antibodies (ADA) lie within the hypervariable complementarity determining regions (CDR) that provide the majority of the binding contacts.
Anti-idiotypic antibodies can be generated to bind specifically to one monoclonal antibody drug.
These highly specialized antibodies can be used to set up pharmacokinetic (PK) assays in different formats to measure free or total drug levels in preclinical and clinical samples, or as positive controls in ADA assays.
The Nobel Prize in Physiology or Medicine 1972
Gerald M. Edelman
Rodney R. Porter
------------------------
Rodney Robert Porter born 8 October 1917 at Newton-le-Willows, Lancashire, England.
He took his Ph.D. at Cambridge under the supervision of Dr. F. Sanger investigating protein chemistry.
He returned to the study of the chemical structure of antibodies leading to the finding of the three fragments produced by splitting with papain in 1958-59. He continued this work at St. Mary’s Hospital Medical School and put forward the peptide chain structure of antibodies in 1962.
-----------------------------------------
Antibodies possess both antigen binding capacity and biological activity. The antigen binding capacity resides in a structure(s) conferred by amino acid sequences in the so-called variable regions. Amino acid differences in this region also confer exquisite specificity, with respect to antigen recognition and binding.
The biological activity of different antibody molecules is the result of amino acid differences in the constant region, although the basic molecular structure of the antibodies is the same. The different constant regions define the isotype (family) of immunoglobulins, IgA, IgD, IgE, IgG and IgM, where Ig refers to the term immunoglobulin.
----------------------------
Discovery by proteolysis
Antibodies possess both an antigen binding capacity and a biological activity.This bifunctional nature of antibodies was initially demonstrated following proteolytic cleavage of antibody. Digestion with papain yields three molecules, two copies of a single antigen binding region, F(ab), and one readily crystallizable fragment (Fc) that cannot bind antigen. Digestion of antibodies with pepsin generates one molecule possessing two antigen binding sites, Fab2. In pepsin digests, the Fc portion is proteolytically degraded.
Biological effector region
The Fc region is determined by the constant region of the antibody and mediates the antibody effector function. Because the constant region of the antibody also defines the antibody isotype, the antibody isotype thus correlates with the antibody’s biological role in an immune response.
Agglutination: antibodies make microbes to stick together to be easily phagocytosed.
Complement activation through classic pathway.
ADCC;
CD40 interaction with CD40L is essential for Ab class switching.
Cytokine release from T-cell may determine the isotype of Ab produce i.e. class
Intravenous immune globulin (IVIG) also contains numerous soluble proteins with biologic activity. DC denotes dendritic cells, FcγR receptor for the Fc portion of IgG, FcRn neonatal Fc receptor, and GR glucocorticoid receptor.
--------------------------------
Fab-mediated activitiesSuppression or neutralization of autoantibodiesSuppression or neutralization of cytokinesNeutralization of activated complement componentsRestoration of idiotypic–anti-idiotypic networksBlockade of leukocyte-adhesion-molecule bindingTargeting of specific immune cell–surface receptorsModulation of maturation and function of dendritic cellsFc-dependent activitiesBlockade of the FcRnBlockade of activating FcγRUp-regulation of inhibitory FcγRIIBImmunomodulation by sialylated IgG
…………….
Fab denotes antigen-binding fragment, Fc crystallizable fragment, FcγR receptor for the Fc portion of IgG, and FcRn neonatal Fc receptor.
Intravenous immune globulin (IVIG) also contains numerous soluble proteins with biologic activity. DC denotes dendritic cells, FcγR receptor for the Fc portion of IgG, FcRn neonatal Fc receptor, and GR glucocorticoid receptor.
--------------------------------
Fab-mediated activitiesSuppression or neutralization of autoantibodiesSuppression or neutralization of cytokinesNeutralization of activated complement componentsRestoration of idiotypic–anti-idiotypic networksBlockade of leukocyte-adhesion-molecule bindingTargeting of specific immune cell–surface receptorsModulation of maturation and function of dendritic cellsFc-dependent activitiesBlockade of the FcRnBlockade of activating FcγRUp-regulation of inhibitory FcγRIIBImmunomodulation by sialylated IgG
…………….
Fab denotes antigen-binding fragment, Fc crystallizable fragment, FcγR receptor for the Fc portion of IgG, and FcRn neonatal Fc receptor.
---------------------------------------------
Immunomodulatory mechanisms of action are less well understood and are likely to differ, depending on the specific autoimmune pathogenesis and individual genetic background. Diseases responding rapidly, but with short-lived duration of efficacy, suggest that high serum levels of therapeutic IgG ‘neutralise’ pathogenic autoantibodies. Other proposed mechanisms include binding or blocking of the antigen-binding site (anti-idiotype), enhancing IgG turn-over, thereby reducing circulating pathogenic IgG, as well as scavenging circulating complement binding sites and interfering with activation of the complement cascade.---------------------------------------------
Several autoimmune disorders are caused by the reaction of IgG to self antigens. Since FcRn extends IgG half-life in the circulation, it can also extend the half-life of these pathogenic antibodies and promote autoimmune disease.[18] New therapies seek to disrupt the IgG-FcRn interaction to increase the clearance of disease-causing IgG autoantibodies from the body. One such therapy is the infusion of intravenous immunoglobulin (IVIg) to saturate FcRn's IgG recycling capacity and proportionately reduce the levels of disease-causing IgG autoantibody binding to FcRn, thereby increasing disease-causing IgG autoantibody removal.[19][20] This strategy of blocking the binding of autoantibodies to FcRn by injecting higher affinity antibodies can help prevent inflammation in response to self antigen.
---------------------------------------------------
Recycling of IgG and serum albumin
FcRn extends the half-life of IgG and serum albumin by reducing lysosomal degradation in endothelial cells[7] and bone-marrow derived cells.[8] IgG, serum albumin and other serum proteins are continuously internalized through pinocytosis. Generally, serum proteins are transported from the endosomes to the lysosome, where they are degraded. The two most abundant serum proteins, IgG and serum albumin are bound by FcRn at the slightly acidic pH (<6.5), and recycled to the cell surface where they are released at the neutral pH (>7.0) of blood. In this way IgG and serum albumin avoids lysosomal degradation. This mechanism provides an explanation for the greater serum circulation half-life of IgG and serum albumin.
Intravenous immune globulin (IVIG) also contains numerous soluble proteins with biologic activity. DC denotes dendritic cells, FcγR receptor for the Fc portion of IgG, FcRn neonatal Fc receptor, and GR glucocorticoid receptor.
--------------------------------
Fab-mediated activitiesSuppression or neutralization of autoantibodiesSuppression or neutralization of cytokinesNeutralization of activated complement componentsRestoration of idiotypic–anti-idiotypic networksBlockade of leukocyte-adhesion-molecule bindingTargeting of specific immune cell–surface receptorsModulation of maturation and function of dendritic cellsFc-dependent activitiesBlockade of the FcRnBlockade of activating FcγRUp-regulation of inhibitory FcγRIIBImmunomodulation by sialylated IgG
…………….
Fab denotes antigen-binding fragment, Fc crystallizable fragment, FcγR receptor for the Fc portion of IgG, and FcRn neonatal Fc receptor.
---------------------------------------------
Immunomodulatory mechanisms of action are less well understood and are likely to differ, depending on the specific autoimmune pathogenesis and individual genetic background. Diseases responding rapidly, but with short-lived duration of efficacy, suggest that high serum levels of therapeutic IgG ‘neutralise’ pathogenic autoantibodies. Other proposed mechanisms include binding or blocking of the antigen-binding site (anti-idiotype), enhancing IgG turn-over, thereby reducing circulating pathogenic IgG, as well as scavenging circulating complement binding sites and interfering with activation of the complement cascade.---------------------------------------------
Several autoimmune disorders are caused by the reaction of IgG to self antigens. Since FcRn extends IgG half-life in the circulation, it can also extend the half-life of these pathogenic antibodies and promote autoimmune disease.[18] New therapies seek to disrupt the IgG-FcRn interaction to increase the clearance of disease-causing IgG autoantibodies from the body. One such therapy is the infusion of intravenous immunoglobulin (IVIg) to saturate FcRn's IgG recycling capacity and proportionately reduce the levels of disease-causing IgG autoantibody binding to FcRn, thereby increasing disease-causing IgG autoantibody removal.[19][20] This strategy of blocking the binding of autoantibodies to FcRn by injecting higher affinity antibodies can help prevent inflammation in response to self antigen.
---------------------------------------------------
Recycling of IgG and serum albumin
FcRn extends the half-life of IgG and serum albumin by reducing lysosomal degradation in endothelial cells[7] and bone-marrow derived cells.[8] IgG, serum albumin and other serum proteins are continuously internalized through pinocytosis. Generally, serum proteins are transported from the endosomes to the lysosome, where they are degraded. The two most abundant serum proteins, IgG and serum albumin are bound by FcRn at the slightly acidic pH (<6.5), and recycled to the cell surface where they are released at the neutral pH (>7.0) of blood. In this way IgG and serum albumin avoids lysosomal degradation. This mechanism provides an explanation for the greater serum circulation half-life of IgG and serum albumin.
No product should be viewed as virally ‘safe’.• Full counselling about risks and benefits must be given to patient, with written information, and this must be recorded in the medical notes.
• Written consent must be obtained prior to therapy and retained in the medical notes.
• A pre-treatment serum sample should be stored, to facilitate ‘lookback’ exercises if required
----------------------------------------
- IVIGs are sterile, purified IgG products manufactured from pooled human plasma and typically contain more than 95% unmodified IgG, which has intact Fc-dependent effector functions and only trace amounts of immunoglobulin A (IgA) or immunoglobulin M (IgM).
- One of biggest advances with IVIG in recent years has been the use of sorbitol-based formulations as opposed to sucrose-based formulations which allow for IV administration with less reactions.
IgA content is variable:
Significant levels of IgA may be important when treating IgAdeficient patients, who may recognize the infused IgA as foreign and respond to it, leading to anaphylactoid responses on subsequent exposure
We of course here talk about replacement therapy.
We of course here talk about replacement therapy.
Dosage regimes range from 0.4g/kg/day for 5 days, through 1g/day for 2 days, to 2g/kg/day as a single dose. Oxford practice is to start all high-dose regimes on the 5-day schedule to assess tolerability, and then increase to 1 g/kg/day for 2 days subsequently. In adults and children, risks of renal impairment and aseptic meningitis are highest with the ultra-rapid infusion schedule of 2g/kg/day, and avoid this if possible
Rapid infusions should be avoided in all elderly patients because of the risks of hyperviscosity.
Infusion rates should follow manufacturers’ guidelines.
There must be no switching of products.Batch numbers must be recorded.
Pre-treatment IgA deficiency and high-titre rheumatoid factors should be excluded, and renal function assessed.
IgA-deficient patients require special care, and should be on products low in IgA.If there is renal impairment to start with, creatinine should be measured daily. If there is a rise of 10% or more, then therapy should be discontinued.FBC should be repeated during the course to ensure that haemolysis does not take place (haptoglobin is a sensitive indicator of intravascular haemolysis).