Immune deficiencies Flashcards
what defect causes X-linked (Bruton) agammaglobulinemia
defect in BTK ( a tyrosine kinase)
how do patients with Bruton agammaglobulinemia present clinically
recurrent bacterial infections and enteroviral infections after 6 months of age (after maternal IgG disappears), absent or underdeveloped lymph nodes and tonsils
what are the significant lab findings for Bruton agammaglobulinemia
absent CD 19+ B cell count, low Ig of all classes, low pro-B
what symptoms do the majority of patients with selective IgA deficiency have
trick question! most patients are asymptomatic;
in some patients you may see Airway and GI infections, Autoimmune disease, Atopy and Anaphylaxis to IgA containing products
what lab findings would you see in patients with selective IgA deficiency
IgA < 7 mg/dL with normal IgG and IgM
what is the causal defect in common variable immunodeficiency
defect in B-cell maturation (due to many causes)
when do patients tend to present with common variable immunodeficiency
20s-30s
what symptoms are seen with common variable immunodeficiency
increased risk of autoimmune disease, bronchiectasis, lymphoma, sinopulmonary infections
what are the lab findings for common variable immunodeficiency
decreased plasma cells, decreased immunoglobulins
name three B-cell immune deficiencies
Bruton’s agammagobulinemia
selective IgA deficiency
common variable immunodeficiency
name four T-cell immune deficiencies
Thymic aplasia (DiGeroge syndrome) IL-12 receptor deficiency autosomal dominant hyper IgE syndrome (Job syndrome) Chronic mucocutaneous candidiasis
what chromosal deletion results in DiGeorge syndrome and what pharyngeal pouches fail as a result
22q11;
3rd and 4th pharyngeal pouches fail to develop as a result
in DiGeorge syndrome what anatomical structures are absent as a result of defective 3rd and 4th pharyngeal pouches
thymus and parathyroids
what is the clinical presentation of DiGeorge syndrome
tetany (hypocalcemia), recurrent viral/fungal infections due to T-cell deficiency, conotruncal abnormalities like tetralogy of Fallot and truncus arteriosus
what are the relevant lab findings for DiGeorge syndrome
low PTH, low Ca, low T cell count
what is the inheritance pattern of IL-12 receptor deficiency
autosomal recessive
what defect is associated with IL-12 receptor deficiency
low Th1 response
what is the clinical presentation of IL-12 receptor deficiency
disseminated mycobacterial and fungal infections; may present after BCG administration
what cytokine is low in IL-12 receptor deficiency
IFN-gamma
what defect is associated with Job syndrome (autosomal dominant hyper IgE syndrome)
STAT3 mutation causes deficiency of Th17 leading to impaired recruitment of neutrophils to sites of infection
what is the clinical presentation of Job syndrome
FATED: coarse Facies, cold (non-inflamed) staphylococcal Abscesses, retained primary Teeth, increased IgE, Dermatological problems like eczema
what are the relevant lab findings in Job syndrome
high IgE, low IFN-gamma
what is the presentation of chronic mucocutaneous candidiasis
noninvasive C. albicans infections of skin and mucous membranes
why can’t the body respond to candidal infection in chronic mucocutaneous candidiasis
T-cell dysfunction (many causes) leading to absent T-cell response in vitro in response to C. albicans and absent cutaneous reaction to Candida antigens
name two common causes of SCID
defective IL-2 receptor gamma chain (X-linked, most common)
adenosine deaminase deficiency (autosomal recessive)
what is the clinical presentation of sCID
failure to thrive; chronic diarrhea; thrush; recurrent viral, bacterial, fungal and protozoal infections
how do you treat SCID
bone marrow transplant (no concern for rejection)
low T-cell receptor excision circles (TREC’s) are associated with what disease
SCID
what causes ataxia-telangiectasia
defects in ATM gene leads to DNA double strand breaks leading to cell cycle arrest
what is the classic triad of ataxia telangiectasia
- cerebellar defects
- spider angiomas
- IgA deficiency
what are the significant lab findings for ataxia telangiectasia
high AFP, low IgA, low IgE, low IgE, lyphopenia and cerebellar atrophy
what causes hyper IgM syndrome
most commonly due to defective CD40L on Th cells => inhibited class switching
what is the inheritance pattern of hyper IgM syndrome
X-linked recessive
what is the clinical presentation of hyper IgM syndrome
severe pyogenic infections early in life, opportunistic infection with pneumocystis, cryptosporidium and CMV
what are the significant lab findings for hyper IgM syndrome
high IgM,
low IgE, low IgG, low IgA
what causes Wiskott-Aldrich syndrome
mutation in WAS gene –> T cells are unable to reorganize their actin cytoskeleton
what is the inheritance pattern of Wiskott-Aldrich syndrome
X-linked recessive
what is the clinical presentation of Wiskot-Aldrich syndrome
WATER: Wiskott-Aldrich, Thrombocytopenic purpura, Eczema, Recurrent infections as well as increased risk of autoimmune disease and malignancy
what are the significant lab findings for Wiskott-Aldrich syndrome
low to normal IgG and IgM
high IgE and IgA
fewer and smaller platelets
name 3 immune deficiencies involving phagocyte dysfunction
Leukocyte adhesion deficiency (type I),
Chediak-Higashi syndrome,
Chronic granulomatous disease
what causes leukocyte adhesion deficiency
defect in LFA-1 integrin (CD18) protein on phagocytes leads to impaired migration and chemotaxis
what is the inheritance pattern of leukocyte adhesion deficiency (type I)
autosomal recessive
what is the clinical presentation of leukocyte adhesion deficiency (type I)
recurrent bacterial skin and mucosal infections, absent pus formation, impaired wound healing, delayed separation of umbilical cord (>30 days)
what happens to neutrophils in leukocyte adhesion deficiency (type I)
increased neutrophil count, but decreased neutrophils at site of infection
what causes Chediak-Higashi syndrome
defect in lysosomal trafficking regulator gene (LYST) leading to microtubule dysfunction in phagoome-lysosome fusion
what is the inheritance pattern of Chediak-Higashi syndrome
autosomal recessive
what is the clinical presentation of Chediak-Higashi syndrome
recurrent pyogenic infections by staph and strep, partial albinism, peripheral neuropathy, progressive neurodegeneration, infiltrative lyphohistiocytosis
what are the significant lab findings for Chediak-Higashi syndrome
giant granules in neutrophils and platelets, pancytopenia, mild coagulation defects
what causes chronic granulomatous disease
defect of NADPH oxidase leading to decreased reactive oxygen species and absent respiratory burst in neutrophils
what is the inheritance pattern of Chronic granulomatous disease
X-linked recessive
what is the clinical presentation of chronic granulomatous disease
increased susceptibility to catalase positive organisms (PLACESS= pseudomonas, listeria, aspergillus, candida, E. coli, S. aureus, Serratia)
how can diagnosis of chronic granulomatous disease be made in the laboratory
abnormal dihydrorhodamine (flow cytometry) test
negative nitroblue tetrazolium dye reduction test (not really done anymore)
