IgG4

IgG4 is one of the four human subclasses of immunoglobulin G (IgG) and typically represents a small fraction of circulating IgG, about 3 to 6 percent. It is produced by plasma cells in response to antigen exposure and is often associated with long-term or repeated antigen contact, such as chronic infections, parasite exposure, or allergen immunotherapy.

A distinctive feature of IgG4 is its ability to undergo Fab-arm exchange, in which half-molecules (comprising one heavy and one light chain) swap with others. This process creates bispecific antibodies that are functionally monovalent for any given antigen, reducing the likelihood of cross-linking immune complexes. As a result, IgG4 has relatively weak effector functions: it binds poorly to certain Fc gamma receptors and activates the classical complement pathway inefficiently, contributing to a generally anti-inflammatory profile. IgG4 can still interact with the neonatal Fc receptor (FcRn) and maintain serum half-life similarly to other IgG subclasses.

In immunology, IgG4 is often associated with blocking antibody activity, particularly in allergy and tolerance. It can compete with IgE for allergen binding and may dampen allergic responses, a feature exploited during some immunotherapies.

Clinically, elevated serum IgG4 levels can be observed in IgG4-related disease (IgG4-RD), a fibroinflammatory condition characterized by infiltration of IgG4-positive plasma cells into tissues and storiform fibrosis. Diagnosis typically relies on tissue histology and clinical features, with serum IgG4 supporting but not being solely diagnostic. IgG4 levels can also rise in other conditions, so interpretation requires context.