IgG4 is the least abundant of the four IgG subclasses and has unique structural and functional properties — including the ability to exchange half-molecules with other IgG4 antibodies (Fab-arm exchange), effectively becoming bispecific and functionally monovalent. This property reduces its ability to form immune complexes and makes IgG4 primarily anti-inflammatory.

Markedly elevated serum IgG4 is the hallmark of IgG4-related disease (IgG4-RD) — a systemic fibro-inflammatory condition that can affect virtually any organ including the pancreas (autoimmune pancreatitis), bile ducts, salivary glands, kidneys, and orbits. IgG4-RD typically responds dramatically to corticosteroid treatment. Elevated IgG4 can also occur in other conditions including atopic disease, parasite infections, and pemphigus.