diagnosis of primary immunodeficiency eli eisenstein, m.d. dept of pediatrics
TRANSCRIPT
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- Diagnosis of Primary Immunodeficiency Eli Eisenstein, M.D. Dept of Pediatrics
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- Ways to Diagnose a Disease Sample the universe Pattern recognition Systematic approach
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- Molecular Medicine, http://www.mm.interhealth.info
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- Cerebellar ataxia Recurrent lung infections IgG2, IgA, IgE deficiency Lavin, Nat Rev Mol Cell Biol 2008
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- Abnormal facies Congenital heart disease Hypocalcemia Lymphocytopenia
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- A greatly over-simplified approach to primary immunodeficieny Humoral Cellular Phagocytic Complement
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- Case 1 11 month old infant Recurrent fevers at least six episodes One episode of gastroenteritis, lasting six days Two episodes of otitis media
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- Relevant history Growth Development Type of infections, and how documented Duration Response to therapy Other illnesses Family history- consanguinity ? Exposure
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- PID ???
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- Case 2 Three year old boy Recurrent lobar pneumonia beginning at six months of age One episode of sepsis caused by Strep. pneumoniae
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- Relevant history Growth Development Type of infections, and how documented Duration Response to therapy Other illnesses Family history Exposure
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- PID ???
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- Humoral Cellular Phagocytic Complement
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- Hallmarks of Humoral Immune Deficiency Respiratory tract infections: Pneumonia, otitis media, sinusitis Encapsulated microorganisms: Pneumococcus, H. influenzae, Staph aureus Chronic diarrhea, other infections, various complications depending on molecular variant Begin after 6 months of age Opportunistic infections uncommon
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- Three Criteria for Diagnosis of Humoral Immune Deficiency Characteristic recurrent infections Low serum concentration of IgG (be sure to check age-appropriate norms) Response to immunizations
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- Type:JPG. Cunningham-Rundles C et al 2005
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- Clinical question What physical finding helps distinguish between B cell positive and B cell negative forms of hypogammaglobulinemia ?
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- Case 3 Eight year old boy Second episode of meningitis caused by Neisseria meningitides
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- PID ???
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- Cellular Phagocytic Complement
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- Complement Pathway Holers in: R Rich et al (eds) Clinical Immunology, 1986, p365
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- Abbas et al, Cellular and Molecular Immunology, 6E
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- Tests for Complement Deficiency Functional tests (e.g., CH50) Measure individual complement components
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- Case 4 On month old boy Failure thrive Persistent diarrhea Pneumonia Pneumocystic jirovecii Sibling died at three months of age of presumed SIDS
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- Cellular Phagocytic
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- Fischer A, Nat Rev Immunol 2:615, 2002
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- Evaluation of cellular immunity Total lymphocyte count (CBC) Presence of thymus Delayed hypersensitivty Flow cytometry Lymphocyte responses to mitogens
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- http://crl.berkeley.edu/flow_cytometry_basic.html Always order a complete blood count with lymphocyte subset analysis.
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- Molecular screening for SCID
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- Phagocytic
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- Three categories of phagocytic cell defects No cells Cells dont know where to go Cells dont know what to do when they get there
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- No cells Several genetic forms including cyclic Diagnosis: complete blood count, peripheral blood smear, bone marrow examination Bacteremia No Pus !! GCSF BMT
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- Cells dont know where to go: Leukocyte adhesion deficiency
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- LAD-1 Clinical features Delayed umbilical cord separation Marked granulocytosis in peripheral blood
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- Incompetent granulocytes Lymphpadenopathy, organomegaly Pneumonia Osteomyelitis Abscesses Staph, Aspergillus Radiographics, 25:1183, 1995
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- NBT test Flow cytometry (DHR)
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- Summary Humoral Complement Cellular Phagocytic
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- Not to forget Molecular diagnosis important for early/prenatal diagnosis and genetic counseling Whole exome sequencing