Immunoglobulin G subclass 4 (IgG4)

Immunoglobulin G subclass 4 (IgG4) is the least abundant subtype of human IgG, making up about 4% of total IgG[1][2][5]. It is characterized by structural features such as a short hinge region (12 amino acids) and unique properties including Fab-arm exchange, giving rise to functionally monovalent molecules[1][2]. Unlike other IgG subclasses, IgG4 has relatively weak binding to activating Fcγ receptors and complement, leading to its largely anti-inflammatory profile[1][3][6]. IgG4 responses are driven by prolonged antigen exposure and T-helper 2 cell signaling[4][1]. Pathologically, IgG4 plays a role in the spectrum of IgG4-related diseases, which are systemic immune-mediated disorders featuring tissue infiltration by IgG4-positive plasma cells, inflammation, and progressive fibrosis in multiple organ systems[4][5][6]. Diagnostic measurement of serum IgG4 and tissue biopsy for IgG4+ plasma cells are essential for clinical management. IgG4’s role is primarily associated with modulation and attenuation of immune responses, rather than direct pathogen clearance, making it a unique element of human immunity[1][3].

Other names

IgG4Human IgG subclass 4Immunoglobulin G4Gamma-4 immunoglobulinIgG-4

Depletion of IgG4-secreting B cells by anti-CD20 agents (e.g., rituximab); Immunosuppression to reduce IgG4 production (e.g., glucocorticoids)