B-cell disorders      
X-linked (Bruton) agammaglobulinemia Defect in BTK (Bruton tyrosine kinase) gene → no B-cell maturation into plasma cells. X-linked recessive (↑ in Boys). Recurrent bacterial (no IgG → no opsonization) and enteroviral, Giardia infections after 6 months of life (↓ maternal IgG). Absent B cells in peripheral blood, ↓ Ig of all classes.

Absent/scanty lymph nodes and tonsils. Live vaccines contraindicated.

Selective IgA deficiency IgE antibodies directed against IgA (anti-IgA antibodies)

Most common 1° immunodeficiency.

Majority Asymptomatic. Can see Airway and GI infections (mucosa), especially viral, Autoimmune disease, Atopy, Anaphylaxis to IgA-containing products, transfusions

Celiac disease is associated with IgA deficiency

↓ IgA with normal IgG, IgM levels. ↑ susceptibility to giardiasis.
Common variable immunodeficiency Defect in B-cell differentiation. Cause is unknown in most cases.

Low immunoglobulin due to B-cell or helper T-cell defects

Usually presents after age 2 and may be considerably delayed; ↑ risk of autoimmune disease, bronchiectasis, lymphoma, sinopulmonary infections. Common pathogens: bacterial, enterovirus, Giardia. ↓ plasma cells, ↓ immunoglobulins.
T-cell disorders      
Thymic aplasia (DiGeorge syndrome) 22q11 deletion; failure to develop 3rd and 4th pharyngeal pouches → absent thymus and parathyroids. Tetany (hypocalcemia), recurrent viral/fungal infections (T-cell deficiency), conotruncal abnormalities (eg, tetralogy of Fallot, truncus arteriosus). ↓ T cells, ↓ PTH, ↓ Ca2+. Thymic shadow absent on CXR.
IL-12 receptor deficiency ↓ Th1 response. Autosomal recessive. Disseminated mycobacterial and fungal infections; may present after administration of BCG vaccine. ↓ IFN-γ.
Autosomal dominant hyper-IgE syndrome (Job syndrome) Deficiency of Th17 cells due to STAT3 mutation → impaired recruitment of neutrophils to sites of infection. FATED: coarse Facies, cold (noninflamed) staphylococcal Abscesses, retained primary Teeth, ↑ IgE, Dermatologic problems (eczema). Bone fractures from minor trauma. ↑ IgE. ↑ eosinophils.
Chronic mucocutaneous candidiasis T-cell dysfunction. Can result from congenital genetic defects in IL-17 or IL-17 receptors. Noninvasive Candida albicans infections of skin and mucous membranes. Neutrophils can still prevent hematogenous spread. Absent in vitro T-cell proliferation in response to Candida antigens. Absent cutaneous reaction to Candida antigens.
B- and T-cell disorders      
Severe combined immunodeficiency Several types including

defective IL-2R gamma chain (most common, X-linked recessive), adenosine deaminase deficiency (adenosine buildup is toxic to lymphocytes – autosomal recessive), cytokine receptor defects, MHC class II deficiency.

Failure to thrive, chronic diarrhea, thrush. Recurrent viral, bacterial, fungal, and protozoal infections. Absent CD3+ T-cells, hypogammaglobulinemia


  • Avoid live vaccines
  • Antimicrobial prophylaxis and IVIG;
  • Sterile isolation
  • Bone marrow/stem cell transplant curative (no concern for rejection).
↓ T-cell receptor excision circles (TRECs). Absence of thymic shadow (CXR), germinal centers (lymph node biopsy), and T cells (flow cytometry).




Defects in ATM gene → failure to detect DNA damage  (especially ionizing radiation) → failure to halt progression of cell cycle → mutations accumulate; autosomal recessive. Triad: cerebellar defects (Ataxia), spider Angiomas (telangiectasia [A]), IgA deficiency (sinopulmonary infections). ↑ AFP.

↓ IgA, IgG, and IgE. Lymphopenia, cerebellar atrophy.

↑ risk of lymphoma and leukemia.

Hyper-IgM syndrome Defective CD40L (most common) or CD40 receptor on Th cells → second signal cannot be delivered to helper T cells during B-cell activation → cytokines necessary for Ig class switching not produced → low IgA, IgG, IgE; X-linked recessive. Severe pyogenic infections early in life, especially in mucosa; opportunistic infection with Pneumocystis, Cryptosporidium, CMV. Normal or ↑ IgM.

↓↓ IgG, IgA, IgE. Failure to make germinal centers.

Wiskott-Aldrich syndrome Mutation in WASp gene; leukocytes and platelets unable to reorganize actin cytoskeleton → defective antigen presentation; X-linked recessive. WATER: Wiskott-Aldrich: Thrombocytopenia, Eczema, Recurrent (pyogenic) infections (defective humoral and cellular immunity).

↑ risk of autoimmune disease and malignancy.

↓ to normal IgG, IgM.↑ IgE, IgA. Fewer and smaller platelets.
Phagocyte dysfunction      
Leukocyte adhesion deficiency (type 1) Defect in LFA-1 integrin (CD18) protein on phagocytes; impaired migration and chemotaxis; autosomal recessive. Recurrent skin and mucosal bacterial infections, absent pus, impaired wound healing, delayed (> 30 days) separation of umbilical cord. ↑ neutrophils in blood. Absence of neutrophils at infection sites.
Chédiak-Higashi syndrome






Defect in lysosomal trafficking regulator gene (LYST). Microtubule dysfunction in phagosome-lysosome fusion; autosomal recessive. PLAIN: Progressive neurodegeneration, Lymphohistiocytosis, Albinism (partial) because melanin cannot migrate from melanocytes, recurrent pyogenic Infections by staphylococci and streptococci because phagocytosis is impaired, peripheral Neuropathy because most distal nerves are not nourished with proteins. Giant granules ([B], arrows) in granulocytes and platelets because granules from Golgi apparatus are not trafficked out. Pancytopenia due to defect in microtubules in mitosis. Mild coagulation defects due to platelet dysfunction.
Chronic granulomatous disease Defect of NADPH oxidase → ↓ reactive oxygen species (eg, superoxide) and ↓ respiratory burst in neutrophils; X-linked form most common > AR. ↑ risk for infection by catalase ⊕ species capable of neutralizing their own H2O2, leaving phagocytes without ROS for fighting infections.


Abnormal dihydrorhodamine (flow cytometry) test (↓ green fluorescence).

Activation of neutrophils with phorbol myristate acetate (PMA) results in oxidation of DHR to a fluorescent compound, rhodamine 123, which can be measured by flow cytometry.

Nitroblue tetrazolium dye reduction test (obsolete) fails to turn blue (turns blue if NADPH oxidase can convert O2 to O2-).

Filipino MD

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