Immunoglobulin G (IgG), the most abundant plasma antibody (8–18 mg/mL), comprises four subclasses (IgG1–4) with distinct effector functions mediated by structural variations in their Fc regions. IgG neutralizes pathogens through Fab-mediated antigen binding and Fc-dependent mechanisms, including complement activation (via C1q binding to IgG1/IgG3) and antibody-dependent cellular cytotoxicity (ADCC) through FcγRIIIa engagement on natural killer cells. IgG’s extended half-life (21 days) arises from pH-dependent FcRn recycling, which also facilitates placental transfer, conferring neonatal immunity.

Clinically, IgG deficiencies manifest as recurrent sinopulmonary infections: selective IgG subclass deficiencies (e.g., IgG2 impairing antipolysaccharide responses), while agammaglobulinemia features near-absent IgG (<200 mg/dL). Autoimmune disorders exhibit subclass-specific involvement-IgG4 drives MuSK myasthenia gravis through functional blockade, whereas IgG1/IgG3 mediate tissue damage in pemphigus via complement activation.

Therapeutically, intravenous IgG (IVIG) at 2 g/kg modulates immunity in Guillain-Barré syndrome by Fc receptor saturation and anti-idiotypic effects. Diagnostic applications leverage IgG’s specificity in serological assays, with subclass profiling guiding immunodeficiency management.