immune work-up for the general pediatrician
DESCRIPTION
Immune Work-Up for the General Pediatrician. Fatima Gutierrez M.D. Goals and objectives. Learn when to Suspect an Immune Deficiency Important Aspects of History Taking Physical Exam Clues Initial Laboratory Work-up When to get an Immune Consult Overview of Specialized Tests. - PowerPoint PPT PresentationTRANSCRIPT
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Fatima Gutierrez M.D.
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Learn when to Suspect an Immune Deficiency
Important Aspects of History Taking Physical Exam Clues Initial Laboratory Work-up When to get an Immune Consult Overview of Specialized Tests
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8 or more new ear infections within one year
2 or more serious sinus infections within 1 year
Two or more months on antibiotics with little effect
2 or more pneumonias within 1 year
Failure of an infant to gain weight or grow normally
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Recurrent, deep skin or or organ abscesses
Persistent thrush in mouth or elsewhere on skin, after age 1
Need for IV antibiotics to clear infections
2 or more deep-seated infections
Family history of Primary Immunodeficiency
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Sinusitis/Pneumonia CF Allergic Rhinitis Anatomy
Low Antibody levels Protein-losing
entropathy, nephropathy
Severe eczema Burns
2° Immunodeficiency Malnourishment Diabetes Sickle Cell
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Primary Immunodeficiencies Can Be Categories by their Defect: Cellular Immunity (T-Cells)
Humoral Immunity (B-Cell)
Phagocytes
Complement
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Bone Marrow
B-lymphocytes
Stem Cell
Plasma cells
Immunoglobulins
T- cells
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T-Cells directly Attack Foreign Antigens
Opportunistic infections Candida sp, Pneumocystis jiroveci
Persistent Thrush Diarrhea/Malabsorption Poor Growth/Failure to Thrive
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Unable to make specific antibodies Multiple / Severe Bacterial Infections Persistent Upper Respiratory Tract
InfectionsStreptococcus, Haemophilis
Usually seen after 6 months when maternal antibodies lost
Growth usually normal unless patient with chronic infections
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Natural Killer Cells – directly attack cells infected with Virus Phagocytes – ingest and kill microorganisms Chronic Granolomatous Disease –
- Infections caused by catalase + organisms
LAD No Pus Gingivitis/Periodontitis Skin Infections, Liver, GI Tract
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Composed of 30 proteins Function in ordered integrated fashion to
defend against infection and produce inflammation
C5- C8 deficiency associated with autoimmune
C1-C4 deficiency Associated with Rheumatic Disorders Pyogenic Infections
C5-C9 Complement deficiency Neiserria Infections
Basic Screen – CH50 – measures function of alternate pathway
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Immunodeficiency
Primary 1:500 – 1:100,000 -
All
1:500 IgA def 1:100,000 SCID 1:200,000 CGD
Secondary 1:300 - HIV
1:5 “unaware” of their HIV
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History Infection HistorySexConsanguinityHistory of Miscarriage/ Death in InfantsPrimary Immune Deficiency in FamilyHistory of Autoimmune/Connective Tissue
d/oEnvironment (Smoke, allergies)Delayed Cord Separation (LAD)HIV risk factors
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Eczema , Wiskott Aldrich or Hyper IgE?
Wiskott Aldrich Thrombocytopenia Small platelets
Hyper IgE -Job Syndrome Skin infections – Staph Sinusitis Coarse Facies Retain Primary Teeth
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Look at MotherIncongentia Pigmenti
Conical Teeth
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Nuclear Factor – kB Essential ModulatorX-LinkedDefect in Cellular Immunity
Variable Immunoglubulin levels Normal B-cell numbers
Recurrent bacterial sinopulmonary and oportunistic Infections
Ectodermal DysplasiaConical TeethTreatment Stem Cell Transplant
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Lymphocyte countAbsolute Lymphocyte count Lymphopenia
Screen for B and T cell DeficienciesLymphocytosis
Omenn Syndrome, Leukocyte Adhesion Deficiency
Neutrophil CountLeukocyte Adhesion Deficiency -
>100,000/mm3 Platelet Size and Number
Wiskott Aldrich
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WBC total x %lymphocytes = Absolute Lymphocyte Count (ALC)
Normal absolute lymphocyte count 10th-90th percentiles (#/μL) by age 0-3months 3400-76006-12months 3900-90001-2 years 3600-8900
Look at normal values based on Age!!
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IgG, IgM, IgA, IgE IgG in young infants less reliable –
largely maternal Lab Variations! Age Adjusted Normals Low IgG in Infant
Hypogammaglobulinemia of Infancy Undetectable IgA
Primary Immune Deficiency High Levels IgM + Absence of other Ig
Hyper IgM IgE
Atopic Disease or Parasitic Illness, Hyper IgE
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Immunoglobulin Immunoglobulin DevelopmentDevelopment
•IgG nadir for infants is age 3 months to 1 year of life•Premature infants will lack adequate maternal IgG•Note in IgG at approximately 6 months of life (maternal vs infant sources)
•IgM production starts immediately after birth•IgA rate of synthesis is slowest
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THYMUS!
May shrink in response to stress/surgery/infection
Thymus continues to grow until teens
Largest size relative to body weight at birth
No Thymus
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T-cell Response Common Antigens
CandidaTrychophytonTetanusDiphtheriaPPD
Anergy (no response) Immune suppr. Meds-
Steroids Infants < 6 months / 2yrs Malnutrition Collagen Vascular Disease Fever- Leukocytosis
Reaction measured at 48 hours
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HIV – DNA when IgG unreliable
ELISA tests IgG Infants have Maternal IgGSevere HypogammaglobulinemiasLiver Disease
Guidelines : www.aidsinfo.nih.gov
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Measurement of Specific T, B,
NK and phagocytic
cells
Measurement of Specific T, B,
NK and phagocytic
cells
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NK Cells
Tcells-
B-Cells
The Case of SCIDThe Case of SCID
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Tests your Body’s Ability to Make Antibodies – Majority of Vaccines activate B-cells in the presence of T-cell
Tests your Body’s Ability to Make Antibodies – Majority of Vaccines activate B-cells in the presence of T-cell
Tests for Common Vaccines
DiphtheriaTetanusStreptococcus
Tests for Common Vaccines
DiphtheriaTetanusStreptococcus
Normal ResponseDiphtheria > 0.1Tetanus > 0.1
Or…4 fold increase of baseline
1 month after vaccine given
Normal ResponseDiphtheria > 0.1Tetanus > 0.1
Or…4 fold increase of baseline
1 month after vaccine given
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Streptococcus – Note minimal responseStreptococcus – Note minimal response
Serotypes in Prevnar:4, 6B, 9V, 14, 18C, 19F, 23FSerotypes in Prevnar:4, 6B, 9V, 14, 18C, 19F, 23F
Serotypes in PCV13Serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F
Serotypes in PCV13Serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F
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Measures the ability of lymphocytes to respond to mitogens and Specific
antigens
Measures the ability of lymphocytes to respond to mitogens and Specific
antigens
Strongly Mitogenic on T-Cells - PHA (Phytohemagluttin) - ConA (Concanavalin-A)
Stimulates T&B cells (Mitogen - Pokeweed
Strongly Mitogenic on T-Cells - PHA (Phytohemagluttin) - ConA (Concanavalin-A)
Stimulates T&B cells (Mitogen - PokeweedAntigens: - Candida -Tetanus - Dipthera
*Prior exposure required for response !! > 2yrs age
Antigens: - Candida -Tetanus - Dipthera
*Prior exposure required for response !! > 2yrs age
Minimal Response
Assay working well
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Early Recognition of Primary Immune Deficiency – Many Primary Immune Deficiencies are Lethal!
Recognize Lab Value Diversity
Don’t forget to look for HIV
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Noroski MD, L., Shearer MD, W. Short Screening for Primary Immunodeficiencies in the Clinical Immunology Laboratory. Clinical Immunology and Immunopathology. Vol. 86, No3, March pp. 2237-245, 1998
Fleisher, Shearer, Kotzin, Schroder. Clinical Immunology – Principles and Practice 2nd Ed. Rich, R.
Schmitz PhD, Folds PhD. Clinical and Laboratory Assesment of Immunity. Journal of Allergy and Immunology 2003: 111:S702-11
American Academy of Allergy Asthma and Immunology – www. aaai.org
Immune Deficiency Foundation – primaryimmune.org
Jeffrey Modell Foundation www. jfmworld.org