Approach of Primary Immune Deficiencies - PowerPoint Presentation

1. Approach ofPrimary Immune Deficiencies دکتر افشین شیرکانیفوق تخصص آسم و آلرژی و بیماری های نقص ایمنیاستادیار دانشگاهعضو آکادمی آسم و آلرژی و ایمونولوژی آمریکا

2. Comparison of hypersensitivity reactionsreactionLymphocyteEffector cells Antibody AntigenTime Complement DiseasesType I B Eosinophils and basophils IgE Allergen 15-20 min-Asthma, atopic dermatitis urticaria Type IIBPMNIgM , IgGSurface Ag?+Hemolytic disease of newbornsType IIIBPMNIgM, IgGSoluble Ag6-8 h+SLEType IVT Macrophages-Intracellular Ag 24-72 h _Tuberculosis

3. Immunity Innate & AdaptiveFirst line of defenseNonspecificRapid onsetNo protective immunityNo memoryPhagocyte- mediatedActivatedVery specificSlowerProtective immunity possibleMemory possibleLymphocyte- mediated

4. Definition Any defect in the integrity of the immune systems It may be congenital or late onsetIt may be inherited or non hereditary It may be in innate or adaptive parts of immune system

5. Components of ImmunitySkin and mucosal barriersInnate immune system (nonspecific)Phagocytic cells, NK cells, complementAdaptive immune system (specific)T and B lymphocytes, antibodies

6. Increasing susceptibility to infections Increasing duration of infections Increasing severity of infection Continuous illness Dependence to antibiotics Infection with opportunistic agents Unusual infectionCharacteristics of infections

7. Eight or more new ear infections within 1 year.Recurrent, deep skin ororgan abscesses.Two or more serious sinus infections within 1 year.Persistent thrush in mouth orelsewhere on skin, after age 1.Two or more months on antibiotics with little effect.Need for intravenousantibiotics to clear infections.Two or moredeep-seated infections.A family history ofPrimary Immunodeficiency.Two or more pneumonias within 1 year.Failure of an infant to gainweight or grow normally.The 10 Warning Signs Of Primary Immunodeficiency

8. Primary Immunodeficiency B cell (Antibody ) systemT cell (cellular ) systemPhagocyte (PMN and mononuclear )Complement

9. Classification of ImmunodeficiencyHumoral (B-cell) – quantitative or qualitative defects in antibody production account for more than 50% of defects.Cellular (T-cell) – usually combined with humoral; account for 20-30%.Phagocytic – defects in migration, or killing; account for ~18%.Complement – account for ~2%

10. About %40 of cases are diagnosed in the first year Another %40 by age 5 years Another %15 by age 16 Only %5 in adulthood About %10 of registered cases are adults Late-onset Patients exhibit CVID

11. Common Risk Factors for Frequent InfectionsDay-care, schoolSecond-hand smokeAtopyAnatomic abnormalities including ciliary defectsRetained foreign bodyGastroesophageal reflueCystic fibrosis

12. Children referred for evaluation for immuno deficiency %50 Turn out to be normal %30 have allergy %10 have a serious but nonimmunologic disorder Only %10 have an immunodeficiency

13. Allergic disorders in contrast to immunodeficiency Absence fo fever Clear nonpurulent discharge Prior history of colic, food intolerance, ezema or other allergic symptoms A Positive family history of allergy A Characteristic seasonal or exposure pattern Poor respons to antibiotic Good respons to antihistamines or bronchodilators

14. Approach for Suspected Immune Deficiency are as following:

15. FAMILY HISTORYConsanguinity of the parents History of a sibling dying early in life of infections Family history of an X-linked or autosomal recessive inheritance of a primary immunodeficiency

16. GENERALComplete blood count, including hemoglobin, differential white blood cell count(ALC , ANC) and morphology, and platelet count,ESRRadiographs to document infection in chest, sinus, mastoids, and long bones, if indicated by clinical historyCultures, if appropriate

17. History Our GuidePredominant B-Cell defectsOnset after maternal antibodies diminish, usually after 5-7 mos, later childhood to adulthood.Bacteria: strep, staph, H.flu; Campylobacter, enteroviruses, giardia, cryptosporidiaRecurrent sinopulmonary infections, chronic GI symptoms, malabsorption, arthritis, viral meningoencephalitisAutoimmunity, lymphoreticular malignancy; thymoma, lymphoma

18. SCREENING TESTS FOR B CELLIMMUNE FUNCTIONQuantitative serum immunoglobulinsSpecific antibodies to vaccine responsesTetanus, diphtheria (IgG1)Pneumococcal and meningococcal polysaccharides (IgG2)Viral respiratory pathogens (IgG1 and IgG3)Other vaccines: hepatitis B, influenza, MMR, polio (killed vaccine)Isohemagglutinins (IgM antibodies to A and B blood groupantigens)B cell quantitation by flow cytometry

19. Laboratory EvaluationQualitative Evaluation of AntibodiesIsohemagglutins – Antibodies to ABO blood-group determinantsAntibodies to tetanus and diptheria glycoproteins and pneumococcal polysaccharides.If low titers, give booster, then repeat titers 4 weeks later.

20. History Our GuidePredominant T-Cell DefectsEarly onset, usually 2-6 mosBacteria, mycobacteria, viruses: CMV, EBV, varicella; fungi, parasites, PCP, -intracellulareFTT, diarrhea, extensive mucocutaneous candidiasisGVHD caused by nonirradiated bloodHypocalcemic tetany in infancy(DiGorje)

21. SCREENING TESTS FOR T CELLIMMUNITYNewborn screening for TREC analysis (not available in iran)Absolute lymphocyte countChest radiograph for thymus shadow in newbornsDelayed skin hypersensitivity to recall antigensQuantification of T cell subsets

22. History Our Guide for B and T cell defficiencyATAXIA TELLANGIECTASIASCIDWISKOTT- ALDERICHE SYNDROME

23. History Our GuideGranulocyte DefectsEarly onset, delayed separation of cord (>8 weeks), poor wound healing(LAD)Bacteria: staph, Pseudomonas, Serratia, Klebsiella; Fungi: Candida, Nocardia, Aspergillus(CGD)Dermatitis, impetigo, cellulitis, abscesses, lymphadenitis, periodontitis, osteomyelits

24. History Our GuideComplement DefectsLate (C5-C9) – Neisserial infections: meningitidis, septic arthritis from gonorrhoeae.Early (C1, C4, and C2) – autoimmune diseaseC3 deficiency – overwhelming sepsis, especially with gram negative organisms

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26. SCREENING TESTS FOR INNATEDEFENSE FACTORSAbsolute granulocyte count, cell morphologySerum total hemolytic complement for classic pathway (CH50), alternative pathway hemolytic activity (AH50)Nitroblue tetrazolium (NBT) test or flow cytometry using dihydrorhodamine (DHR) « Staphylococcus aureus, Serratia marcescens, and Aspergillus”Flow cytometry for leukocyte adhesion molecules (CD11/CD18and CD15a)IgE (JOB )

27. B Cell ImmunodeficienciesBruton Bruton’ s (X-linked) AgammaglobulinemiaAutosomal Recessive Hyper-IgM Syndrome X-linked Lymphoproliferative SyndromeTransient Hypogammaglobulinemia of InfancyCommon Variable Immunodeficiency (CVID)Selective IgA Deficiency IgG Subclass Deficiency

28. General Management of Patients withImmunodeficiencyAvoid transfusions with blood products unless they are irradiated and cytomegalovirus-negative.Avoid live virus vaccines, especially in patients with severe T-cell deficiencies or agammaglobulinemia, and in household members.Use prophylaxis to Pneumocystis jiroveci (carinii) in T-cell immunodeficiency, and in X-linked hyper-IgM, consider antifungal prophylaxis in T-cell immunodeficiency.Follow pulmonary function in patients with recurrent pneumonia.Use chest physiotherapy and postural drainage in patients with recurrent pneumonia.

29. Consider using prophylactic antibiotics because minor infections can quickly disseminate.Examine diarrheal stools for Giardia lamblia and Clostridium difficile.Avoid unnecessary exposure to individuals with infection.Boil water for T-cell defects and hyper-IgM syndrome (Cryptosporidium risk).Use immunoglobulin for severe antibody deficiency states (400–600mg/kg q3–4 wk IV).BMT for T cell and Innate defect

30. When IgG level are normal or near normal but Antibody deficiency is susceptible IgG subclasses should be measured (IgG=70%, IgG 2 =20%, IgG3=7%, IgG4=3%) Antibody function should be measured In patient with selective IgA deficiency IgG subclasses should be measured Many IgA deficiency patients have IgG2 subclass deficiency

31. In older children and adults , a total Ig level above 800 mg/ dl with normal screening antibody test excludes antibody deficiency Total Ig (IgG+IgM +IgA )< 400 or IgG level <200 mg /dl usually indicates antibody immunodeficiency

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