X-Linked Agammaglobulinemia: Pathogenesis and clinical findings The epidemiology of this disease is 1/340,000 births and roughly double this rate in male births. 40% of patients diagnosed with XLA have a family history of the disease. The remainder likely arises via sporadic mutation. Signs of immunodeficiency may appear 3-9 months after birth, due to a decline in maternal antibody. Genetic Predisposition -> Mutation of BTK gene on the X chromosome -> Impaired function of BTK, a signal transduction protein involved in B cell maturation -> Decreased Phospholipase C signaling downstream of BTK -> Impaired maturation of B cells from precursor cells -> Impaired B cell function -> Inability to produce all classes of immunoglobulin proteins (antibodies) -> Complete deficiency in adaptive humoral immunity Signs/Symptoms/Findings: • Absence of mature B cells (CD19+) and plasma cells in blood and bone marrow • Absence of tonsils, adenoids, +/- lymph nodes • Increased susceptibility to infection, especially bacterial infections (e.g. bacterial pneumonia) • Decreased or undetectable levels of IgA, IgG, and IgM • Decreased or undetectable antibodies in response to immunizations and common antigens #Agammaglobulinemia #XLinked #pathophysiology #immunology
