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Immunoglobulin Therapy in Primary Immunoglobulin Therapy in Primary

Immunoglobulin Therapy in Primary - PowerPoint Presentation

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Immunoglobulin Therapy in Primary - PPT Presentation

Immunodeficiencies By Angela Migowa Pediatric Rheumatologist Aga Khan University EPLS Instructor RCUK MBCHB UON MMED Pediatrics and Child Health AKUHN Pediatric Rheumatology McGill ID: 909650

frequent immunoglobulin rare therapy immunoglobulin frequent therapy rare infections administration patients immunol deficiency 2013 iga effects severe ivig antibodies

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Slide1

Immunoglobulin Therapy in Primary Immunodeficiencies

By Angela MigowaPediatric Rheumatologist Aga Khan UniversityEPLS Instructor (RCUK) MBCHB (UON), MMED Pediatrics and Child Health (AKUHN), Pediatric Rheumatology (McGill)

Slide2

Slide3

Objectives

To understand the mechanism of action of Immunoglobulin Therapy in management of Primary ImmunodeficienciesTo describe the indications of Immunoglobulin Therapy in primary immunodeficiencies

To outline the formulations and dosing of immunoglobulins

Slide4

OutlineHistorical perspective of Immunoglobulin

TherapyThe status of Immunoglobulin Therapy in Africa and KenyaMode of action of Immunoglobulin TherapyIndications of Immunoglobulin Therapy in PID’sDosing, Formulation and Toxicity of Immunoglobulin TherapyQuestionsSummary

Slide5

The Great Overlap

Slide6

Definitions

Therapeutic immunoglobulin is a blood product derived from thousands of healthy, pooled donors and preparations are made up of almost exclusively IgG (although commercially available products also contain trace amounts of IgA and IgM).Schwab I et al. Nat Rev Immunol. 2013;13(3):176–189.

Sandomenico A et al. Mol Biotechnol. 2013;54 (3):983–995.

Slide7

Historical PerspectiveS

erum from animals or convalescent humans for treatment and prevention by end of the 19 century.Purification of Immunoglibulin G (IgG) in the 1940’s Human Ig

subcut replacement therapy first performed in 1952, by Bruton, in patient with agammaglobulinemia Since

the 1960’s, different

intravenous preparations

S

ubcutaneous

administration

increasingly

used in the last 10 to 15

years

Berger M et al. United States: Academic Press; 2014. pp. 307–377

.

Wasserman RL et al. Allergy

Clin

Immunol.2015;135(2

Suppl

)

Slide8

Raising Awareness to improve the current status of PID on the Continent: The A Project

56 African Countries

Gross undiagnosis

and misdiagnosis of PIDs on the continent

Caregivers cannot easily access congresses/resources

Patients have no voice

Urgent need to improve lives of African PID patients

Urgent need to document the African genetic PID landscape

Courtesy Prof J. Chipeta

Slide9

Slide10

Mode of Action of IVIG

Slide11

Slide12

Indications of Therapy

Slide13

Goal of Therapy

The goal of therapy is to provide levels of functional serum IgG expected in normal subjects, and sufficient amounts of passive antibodies capable of neutralization and opsonization of broad categories of infectious pathogens.Albin S et al. Immunotherapy. 2014; 6(10): 1113–1126

.

Slide14

Pre-requisites to IVIG Administration

Improved education among healthcare workersAppropriate patient workup before initiation of therapy. Baseline immunoglobulin levelsSpecific antibodies to prior vaccinations

Screening for potential blood borne infections eg HIV, Hepatitis

Slide15

Administration

Currently two routesIntravenous (IVIG), first approved for use in 1979 subcutaneous (SCIG), first approved for use in 2006 [80].Biochemical properties should be considered in the context of unique patient profiles

.Starting in doses between 400 and 600 mg/kg every 3–4 weeks intravenously or twice weekly subcutaneouslyImmune Deficiency Foundation. Immunoglobulin products. www.primaryimmune.org/treatment-information/immunoglobulin-products/

Slide16

Indications

Slide17

X-Linked Agammaglobulinemia

Caused by a mutation in the gene for Bruton’s tyrosine kinase, which leads to a marked reduction in B cells and agammaglobulinemia.Present with recurrent bacterial infections such as otitis, sinusitis and pneumonia, with physical exam findings of absent or barely detectable tonsillar

lymph node tissue. Immunoglobulin replacement proven successful in preventing infections and allowing patients to lead healthy and productive lives.Debost-Legrand A et al. Gene. 2013;527(1):

426–428

.

Slide18

Common Variable Immunodeficiency

Hypogammaglobulinemia with a variety of T cell abnormalitiesClinical manifestations include infections, autoimmunity and cancer.Infections from encapsulated, atypical bacteria and parasites eg GiardiaImmunoglobulin replacement may be used in conjunction with prophylactic antibiotics

.Immunoglobulin does not primarily treat the noninfectious manifestations of CVIDCunningham-Rundles C et al. Blood. 2010;116(1):7–15.

Slide19

Hyper IgM Syndromes

Hyper IgM syndromes (HIGM) are a group of antibody deficiencies characterized by defective CD40/CD40L interactionsImmunoglobulin therapy is indicated for all forms Additional treatments include prophylactic antibiotics GCSF for neutropenia and bone marrow transplant

Quartier P et al. Clin Immunol. 2004;110(1):22–29.

Slide20

Wiskott Aldrich Syndrome

Wiskott-Aldrich syndrome is a triad of recurrent infections, microthrombocytopenia and eczemaPatients also are predisposed to autoimmune disorders and malignancies

It is an X-linked disease caused by mutations in the WASP gene. WASP protein is involved in the transduction of signals from receptorsBone marrow transplant is the only cure Supportive treatment includes immunoglobulin therapy, antimicrobials, platelet transfusions

Massaad

MJ et al.

Ann NY Acad Sci. 2013;1285:26–43.

Slide21

Severe Combined Immunodeficiency

Severe combined immunodeficiency (SCID) is a heterogeneous group of genetic disorders characterized by significant T-cell deficiency, with variable production and function of B and NK cells [67].Infants born are normal at birth, but infection and failure to thrive manifest as passively transferred maternal antibodies begin to waneConsidered

a pediatric emergencyWhile awaiting transplant, patients are given prophylactic antibiotics and immunoglobulin replacement.Bousifa A et al. Front

Immunol

. 2011;2:54

.

Dvorak CC et al. J

Clin

Immunol

. 2013;33(7):1156–1164.

The Bubble Boy

Slide22

When to be cautious with IVIG therapy

Slide23

Selective Ig A Deficiency

Asymptomatic patients with selective IgA deficiency do not need immunoglobulin treatmentRecurrent infections should be treated as neededSelective IgA deficiency is not an indication for immunoglobulin, and administration may lead to anaphylaxis or similarly severe reactions for IgA-deficient patients who have IgG or IgE

anti-IgA antibodies Burks AW et al. N Engl J Med. 1986;314(9):560–564.

Slide24

Toxicity

Slide25

Adverse Effects

Symptoms and signs

FrequencyRelated to infusion rate

Chills

Frequent

Headache

Frequent

Dyspnea

Frequent

Chest pain or tightness

Frequent

Back pain

Frequent

Fatigue and malaise

Frequent

Fever

Frequent

Hypotension or hypertension

Frequent

Myalgia

Frequent

Nausea and vomiting

Frequent

Pruritus

Frequent

Skin rash and hives

Frequent

Flu-like symptoms

Frequent

Tachycardia

Frequent

Types and frequency of adverse effects associated with administration of intravenous immunoglobulin

https

://

www.ncbi.nlm.nih.gov/pmc/articles/PMC5823061

Slide26

Adverse Effects

Symptoms and signs

FrequencyTachycardiaFrequent

Central nervous system

Aseptic meningitis

Rare

Severe headache

Rare

Renal

Acute renal failure (acute tubular necrosis)

Rare (usually associated with sucrose as a stabilizer)

Azotemia

Rare

Thromboembolic events

Thrombosis and cerebral infarction

Rare

Myocardial infarction

Rare

Pulmonary thromboembolism

Rare

Posterior leukoencephalopathy syndrome

Rare

Types and frequency of adverse effects associated with administration of intravenous immunoglobulin

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5823061/

Slide27

Imperatives for the Primary Care Provider

Accurate

record of immunizations

Maintain

accurate and ongoing growth charts

Complete

family history with genogram

Follow-up

after antibiotic treatment (i.e. did what you

prescribe

work?)

Slide28

Questions?

Slide29

Summary

Slide30

Slide31

Thank you

Slide32

Summary