Immunoglobulin G4 (IgG4)

Immunoglobulin G4 (IgG4) is one of the four subclasses of immunoglobulin G (IgG), representing less than 5% of total serum IgG in healthy individuals. It plays a unique role in immune regulation and is notably implicated in IgG4-related disease (IgG4-RD).

• Molecular weight: ~150 kDa
• Serum concentration: 0.05–1.5 g/L
• Comprises <5% of total IgG
• Half-life: ~21 days
• Poorly activates complement via the classical pathway

• Fab-arm exchange: IgG4 molecules can exchange half-molecules, leading to functionally monovalent antibodies
• Low affinity for Fc receptors and C1q → reduced pro-inflammatory activity

• Generally considered anti-inflammatory
• Acts as a “blocking antibody” in allergy desensitization therapy
• May downregulate immune responses by competing with other IgG subclasses

• IgG4-related disease (IgG4-RD)
• Atopic dermatitis
• Parasitic infections
• Certain cancers (e.g., pancreatic)
• Chronic inflammatory diseases (non-specific)

• Often not clinically significant unless associated with other immunoglobulin deficiencies

• Serum IgG4 quantification by nephelometry or ELISA
• Used in diagnosis and monitoring of IgG4-RD, but not diagnostic alone

• Elevated serum IgG4 in ~60–70% of cases
• Tissue infiltration with IgG4+ plasma cells is key for diagnosis
• Not all patients with elevated IgG4 have IgG4-RD, and vice versa

• Immunoglobulin G4-related disease
• Allergic diseases
• Parasitic infections
• Multicentric Castleman disease
• Autoimmune pancreatitis
• Chronic sinusitis