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Immune Work-Up for the General Pediatrician

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Presentation on theme: "Immune Work-Up for the General Pediatrician"— Presentation transcript:

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


4 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

5 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


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

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

9 T- cells Plasma cells Immunoglobulins B-lymphocytes Bone Marrow
Stem Cell T- cells

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

11 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

12 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

13 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

14 Stats: Immunodeficiency Primary Secondary 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


16 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 Passive cigarrette smoke inhalation can predispose to otitis media, pneumonia, bronchitis. Allerigies can worsen congestion, predispose to sinusitis and otitis media

17 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 Lack of tonsils/lymph nodes – X-linked aggamaglobulinemia Lack of Pus- Leukocyte Adhesion Disorder Chronic Eczema – Wiscott Aldrich, Hyper IgE

18 Physical Exam: Conical Teeth Look at Mother Incongentia Pigmenti

19 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

20 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

21 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 6-12months 1-2 years Look at normal values based on Age!!

22 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

23 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

24 X-Ray THYMUS! May shrink in response to stress/surgery/infe ction
Thymus continues to grow until teens Largest size relative to body weight at birth No Thymus

25 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 High False negative

26 HIV TestIng HIV – DNA when IgG unreliable ELISA tests IgG
Infants have Maternal IgG Severe Hypogammaglobulinemias Liver Disease Guidelines :

27 Abnormal Labs or Concerning clinical Picture: Immunology consult

28 Measurement of Specific T, B, NK and phagocytic cells
Phenotyping Measurement of Specific T, B, NK and phagocytic cells


30 Lymphocyte studies

31 The Case of SCID NK Cells Tcells- B-Cells

32 4 fold increase of baseline 1 month after vaccine given
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 Majority of Vaccines T-Dependent Normal Response Diphtheria > 0.1 Tetanus > 0.1 Or… 4 fold increase of baseline 1 month after vaccine given

33 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 Test not accurate if patient received IVIG (Wait 3-4 weeks) Bacteriophage X1074 if patients have recenlty received IVIG

34 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 Phytohemagluttin- isolated from red kidney bean ConA- from jack beans Pokeweed mitogen from root Antigens: - Candida -Tetanus - Dipthera *Prior exposure required for response !! > 2yrs age

35 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

36 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 , 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. Immune Deficiency Foundation – Jeffrey Modell Foundation www.

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