Immunodeficiencies Flashcards
Selective IgA Deficiency:
Unknown defect; Decreased IgA with normal IgG, IgM and B cell counts
Airway and GI infections, AI dz, Atopy, Anaphylaxis to IgA containing products (blood transfusion)
Presentation of IgA Deficiency
Patients with IgA deficiency are susceptible to what disease?
Giardiasis
XLR defect in the BTK tyrosine kinase gene leading to no B-cell maturation
X-linked (Bruton) Agammaglobulinemia
Absent B cells in peripheral blood, decrease Ig of all classes
Absent/scanty LNs and tonsils
live vaccines CI
Lab findings in Bruton’s Agammaglobulinemia:
Recurrent bacterial and enteroviral infections after 6 mos. d/t decreased maternal IgG
Presentation of Bruton Agammagloublinemia
Defect in B cell differentiation
Common Variable Immunodeficiency
Lab findings in Common Variable Immunodeficiency:
Decreased plasma cells and immunoglobulins
Presentation of Common Variable Immunodeficiency:
Presents after age 2 and may be delayed
Increased risk of AI dz, bronchiectasis, lymphoma and sinopulmonary infections
Thymic Aplasia (Digeorge Syndrome:
22q11 deletion–failure of the 3rd and 4th branchial pouches to develop leading to an absent thymus and absent parathyroids
Lab findings in Thymic Aplasia:
decreased T cells, PTH and Calcium; Absent thymic shadow on CXR
Clinical presentation of Thymic Aplasia
Tetany, recurrent viral/fungal infections, conotruncal abnormalities
IL-12 receptor deficiency:
AR Decreased Th1 response
Lab findings in IL-12 deficiency:
Decreased IFN-gamma
Clinical presentation of IL-12 receptor deficiency:
Disseminated mycobacterial and fungal infections; may present after the administration of the BCG vaccine
AD Deficiency of Th17 cells d/t STAT3 mutation leading to impaired recruitment of neutrophils to the site of infection
AD Hyper-IgE syndrome (Job):
Lab findings in Hyper-IgE syndrome:
Increased IgE and eosinophils
coarse facies, non-inflamed Staph abscesses, retained primary teeth, dermatologic problems
Hyper-IgE syndrome:
T cell dysfunction d/t congenital defects in IL-17 or IL-17 receptors
Chronic mucocutaneous candidiasis:
Absent in vitro T-cell proliferation response to candida antigens; Absent cutaneous reaction to candida antigens
Lab findings of Chronic mucocutaneous candidiasis
Defective IL-2R gamma chain (XLR)
Adenosine Deaminase deficiency (AR)
SCID
Lab findings in SCID:
Decreased TCR excision circles
Absent thymic shadow, germinal centers, and T cells
Clinical presentation of SCID:
FTT, chronic diarrhea, thrush
Recurrent viral, bacterial, fungal and protozoal infections
Avoid live vaccines, antimicrobial prophylaxis and IVIG, BM transplant
AR Defect in ATM gene leading to failure to detect DNA damage –> failure to halt progression of cell cycle –> accumulation of mutation
Ataxia Telangiectasia
Increased AFP
Decrease IgA, IgE, and IgE
Lymphopenia, cerebellar atrophy
Increased risk of lymphoma and leukemia
Lab finding of Ataxia Telangiectasia
Cerebellar defects, spider angioma, IgA deficiency
Ataxia, telangiectasias, IgA deficiency, poor smooth pursuit of moving target
Clinical presentation of Ataxia Telangiectasia
Hyper-IgM Syndrome:
XLR Defective CD40L on Th cells leading to a class-switching defect
Lab values in Hyper-IgM Syndrome:
Normal or increased IgM
Decrease IgG, IgA, IgE
Failure to make germinal centers
Wiskott Aldrich Syndrome
XLR Mutation in WASp gene;
Leukocytes nd platelets are unable to recognize actin skeleton–> defecting atigen presentation
Lab findings in Wiskott Aldrich Syndrome:
Decreased to normal IgG, IgM
Increased IgE and IgA
Fewer and smaller platelets
Clinical manifestation of Wiskott-Aldrich Syndrome:
Thrombocytopenia, Eczema, Recurrent pyogenic infections
Increased risk of AI Dz and malignancy
Leukocyte Adhesion Deficiency (LAD):
AR defect in LFA-1 integrin (CD18) protein on phagocytes leading to impaired migration and chemotaxis
Lab findings in LAD:
Increased neutrophils in blood
Absence of neutrophils at infection site, noabscess formation
Clinical manifestations of LAD:
recurrent mucosal and skin infections
absent pus
delayed separation of the umbilical cord (>30 days)
impaired wound healing (thin blue scars)
Chediak-Higashi Syndrome:
AR defect in lysosomal trafficking regulator gene (LYST)
Microtubule dysfunction in phagosome-lysosome fusion
Lab findings in Chediak-Higashi syndrome:
Giant granules in granulocytes and platelets
Pancytopneia
Mild coagulation defects
Clinical Presentation of Chediak Higashi Syndrome:
Progression neurodegeneration
Lymphohistiocytosis
Partial Albinism
Recurrent pyogenic infections by staphylococcal and streptococcal organisms
Peripheral neuropathy
Chronic Granulomatous Disease:
XLR defect in NADPH oxidase leading to a decrease in the formation of reactive oxygen species (superoxide) and decreased respiratory burst from neutrophil
Lab findings in CGD:
Abnormal dihydrorhodamine test (decreased green fluorescence) and Nitroblue tetrazolium dye reduction test fails to turn blue
Clinical presentation of CGD:
Increased susceptibility to catalase + organisms
C3 deficiency:
Low C3; decreased opsonization of encapsulated bacteria
Clinical presentation of C3 deficiency
Recurrent sinus infections ad respiratory tract infections with encapsulated organism
Increased susceptibility to type III HS reactions
Paroxysmal Nocturnal Hemoglobinuria (PNH):
Defect in the PIGA gene encoding for the anchors for complement inhibitors (DAF/CD55) and membrane inhibitor of reactive lysis (MIRL/CD59)
Clinical presentation of PNH:
Complement mediated lysis of RBCs during acidic conditions (sleeping)
Terminal complement deficiencies (C5-9):
Increase susceptibility to recurrent Neisseria bactermia
Early complement deficiencies (C1-C4):
Increased risk of severe, recurrent pyogenic sinus and respiratory tract infections
Increased risk of SLE
