Clinical utility of serum IgG4 measurement.

This article will review the structure and function of IgG4, methods of measuring serum IgG4 concentrations, clinical conditions associated with increased and decreased serum IgG4, and the test characteristics of serum IgG4 in the diagnosis and management of Immunoglobulin G4-Related Disease (IgG4-RD). The four subclasses of IgG were discovered in 1964 through experiments on monoclonal IgG in patients with myeloma. Since 2001, interest in measuring serum IgG subclasses has increased dramatically due to the emergence of IgG4-RD, a multisystem fibroinflammatory condition wherein polyclonal serum IgG4 concentration is increased in approximately 70% of cases. Increased serum IgG4 typically manifests as a restriction in the anodal gamma region on serum protein electrophoresis, often with beta-gamma bridging, and can be mistaken as a monoclonal protein or polyclonal increase in IgA. Limitations of current clinical methods used in quantitation of serum IgG4 concentrations will be discussed, including the common immunonephelometric assays and LC-MS/MS based assays. Polyclonal IgG4 elevation is not specific for IgG4-RD, and may also occur in conditions such as eosinophilic granulomatosis with polyangiitis (EGPA), lymphoma, and multicentric Castleman disease (MCD). Race and gender differences also affect interpretation of serum IgG4 concentrations, for instance Asians have a higher serum IgG4 concentration than Whites and males have a higher concentration than females.