IgG4-related disease: History and overview

Abstract

IgG4-related disease (IgG4-RD) is a recently established disease concept closely associated with increased levels of IgG4 in serum and elevated concentrations of IgG4+ plasma cells within affected tissues. IgG4-RD is currently considered to be an immune-mediated condition with possible contributions from autoimmunity, but the precise mechanisms remain to be established. The characteristic features of IgG4-RD can be summarized as follows: (1) systemic organ involvement, in which individual organ manifestations may require different approaches to management; (2) the ability to involve multiple organs either simultaneously or in a metachronous fashion; (3) imaging findings of swelling, nodules, or increased organ wall thickness; (4) elevated serum IgG4 concentrations, frequently to dramatic levels; (5) lymphoplasmacytic infiltrate within affected organs, characterized by abundant IgG4-bearing plasma cells; and, (6) favorable response to glucocorticoid therapy in most cases. The establishment of this entity originated with the discovery of high serum IgG4 concentration and marked IgG4-bearing plasma cell infiltration in patients with autoimmune pancreatitis (AIP). This was followed by the recognition of systemic extra-pancreatic lesions complicating AIP that exhibited the same clinical features, such as IgG4-bearing plasma cell infiltration and a favorable response to glucocorticoid therapy. These observations suggested a common pathophysiological background for AIP and its extra-pancreatic lesions and culminated in the proposal of a systemic disease that encompassed IgG4, AIP, and systemic lesions. Although considerable advances in IgG4-RD diagnosis and treatment are being made, the etiology, exact disease spectrum and long-term outcomes of this new disease entity require further study.