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Immune Work-Up for the General Pediatrician

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.

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Immune Work-Up for the General Pediatrician

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  1. Immune Work-Up for the General Pediatrician Fatima Gutierrez M.D.

  2. 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

  3. When to suspect: • 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

  4. When to suspect • 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

  5. Zebras among us • Sinusitis/Pneumonia • CF • Allergic Rhinitis • Anatomy • Low Antibody levels • Protein-losing entropathy, nephropathy • Severe eczema • Burns • 2° Immunodeficiency • Malnourishment • Diabetes • Sickle Cell

  6. Basic immunology • Primary Immunodeficiencies Can Be Categories by their Defect: • Cellular Immunity (T-Cells) • Humoral Immunity (B-Cell) • Phagocytes • Complement

  7. Immunoglobulins Plasma cells B-lymphocytes Bone Marrow Stem Cell T- cells

  8. T-Cell Defects • T-Cells directly Attack Foreign Antigens • Opportunistic infections • Candida sp, Pneumocystis jiroveci • Persistent Thrush • Diarrhea/Malabsorption • Poor Growth/Failure to Thrive

  9. B-Cell Defect • Unable to make specific antibodies • Multiple / Severe Bacterial Infections • Persistent Upper Respiratory Tract Infections • Streptococcus, Haemophilis • Usually seen after 6 months when maternal antibodies lost • Growth usually normal unless patient with chronic infections

  10. Phagocyte defects • 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

  11. Complement defects • 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

  12. Stats: • 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

  13. Stage 1: History & Exam • History • Infection History • Sex • Consanguinity • History of Miscarriage/ Death in Infants • Primary Immune Deficiency in Family • History of Autoimmune/Connective Tissue d/o • Environment (Smoke, allergies) • Delayed Cord Separation (LAD) • HIV risk factors

  14. Physical exam • Eczema , Wiskott Aldrich or Hyper IgE? • Wiskott Aldrich • Thrombocytopenia • Small platelets • Hyper IgE -Job Syndrome • Skin infections – Staph • Sinusitis • Coarse Facies • Retain Primary Teeth

  15. Physical Exam: Conical Teeth Look at Mother Incongentia Pigmenti

  16. NemO: Not just a fish • Nuclear Factor – kB Essential Modulator • X-Linked • Defect in Cellular Immunity • Variable Immunoglubulin levels • Normal B-cell numbers • Recurrent bacterial sinopulmonary and oportunistic Infections • Ectodermal Dysplasia • Conical Teeth • Treatment Stem Cell Transplant

  17. STAGE 1: important info in the CBC • Lymphocyte count • Absolute Lymphocyte count • Lymphopenia • Screen for B and T cell Deficiencies • Lymphocytosis • Omenn Syndrome, Leukocyte Adhesion Deficiency • Neutrophil Count • Leukocyte Adhesion Deficiency - >100,000/mm3 • Platelet Size and Number • Wiskott Aldrich

  18. ALC below 2000 abnormal in Infants! • WBC total x %lymphocytes = Absolute Lymphocyte Count (ALC) • Normal absolute lymphocyte count 10th-90th percentiles (#/μL) by age • 0-3months 3400-7600 • 6-12months 3900-9000 • 1-2 years 3600-8900 • Look at normal values based on Age!!

  19. Stage 1: Immunoglobulins • 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

  20. Immunoglobulin Development • 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

  21. X-Ray • 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

  22. DelayeD Hypersensitivity SkIN Test • T-cell Response • Common Antigens • Candida • Trychophyton • Tetanus • Diphtheria • PPD • Anergy (no response) • Immune suppr. Meds- Steroids • Infants < 6 months / 2yrs • Malnutrition • Collagen Vascular Disease • Fever- Leukocytosis Reaction measured at 48 hours

  23. HIV TestIng • HIV – DNA when IgG unreliable • ELISA tests IgG • Infants have Maternal IgG • Severe Hypogammaglobulinemias • Liver Disease • Guidelines : www.aidsinfo.nih.gov

  24. Abnormal Labs or Concerning clinical Picture:Immunology consult

  25. Phenotyping Measurement of Specific T, B, NK and phagocytic cells

  26. Lymphocyte studies

  27. The Case of SCID NK Cells Tcells- B-Cells

  28. Humoral Immune Panel Tests your Body’s Ability to Make Antibodies – Majority of Vaccines activate B-cells in the presence of T-cell Tests for Common Vaccines Diphtheria Tetanus Streptococcus Normal Response Diphtheria > 0.1 Tetanus > 0.1 Or… 4 fold increase of baseline 1 month after vaccine given

  29. Humoral Immune Panel Streptococcus – Note minimal response Serotypes in Prevnar: 4, 6B, 9V, 14, 18C, 19F, 23F Serotypes in PCV13 Serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F

  30. lymphocyte proliferation Assays: (Mitogens and 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 Minimal Response Assay working well Antigens: - Candida -Tetanus - Dipthera *Prior exposure required for response !! > 2yrs age

  31. Take Home message • Early Recognition of Primary Immune Deficiency – Many Primary Immune Deficiencies are Lethal! • Recognize Lab Value Diversity • Don’t forget to look for HIV

  32. References • 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

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