Immunodeficiency Syndromes

Immunodeficiency syndromes are classified as primary (congenital/genetic) or secondary (acquired). Primary immunodeficiencies (PIDs) are genetic defects in immune system components, usually presenting in childhood with recurrent, severe, or unusual infections. They are classified by which immune component is affected: B-cell deficiencies (humoral — most common PIDs, ~50%) present with recurrent sinopulmonary infections from encapsulated bacteria (S. pneumoniae, H. influenzae) beginning after 6 months of age (maternal IgG wanes). Examples: X-linked agammaglobulinemia (Bruton — BTK mutation; absent B cells and all immunoglobulins; boys only), common variable immunodeficiency (CVID — most common symptomatic PID; low IgG ± IgA/IgM; onset teens-30s; increased autoimmune and malignancy risk), selective IgA deficiency (most common PID overall, 1:500; usually asymptomatic; risk of anaphylaxis with blood products containing IgA). T-cell deficiencies present with viral, fungal, and intracellular bacterial infections: DiGeorge syndrome (22q11.2 deletion — absent thymus, hypoparathyroidism, cardiac defects, facial dysmorphism), severe combined immunodeficiency (SCID — absent T and B cell function; 'bubble boy' disease; fatal without stem cell transplant). Phagocytic defects: chronic granulomatous disease (CGD — NADPH oxidase deficiency; cannot generate reactive oxygen species to kill catalase-positive...