title: IgG4-related disease and the kidney.
abstract: IgG4-related disease (IgG4-RD) is a systemic fibroinflammatory condition that involves almost every organ system. In this Review, we summarize current knowledge of IgG4-RD and its most frequent manifestations in the kidney—IgG4-related tubulointerstitial nephritis (TIN) and membranous glomerulonephropathy (MGN). Diagnosis of IgG4-RD relies on histopathology: the typical features are a dense lymphoplasmacytic infiltrate and storiform fibrosis. A high percentage of plasma cells observed within lesions stain positively for IgG4. IgG4-related TIN bears the hallmark pathological findings of IgG4-RD; distinctive radiographic characteristics are also frequently observed with use of contrast-enhanced CT. MGN secondary to IgG4-RD seems to be distinct from idiopathic MGN. Humoral and cell-mediated immunity seem to have roles in the pathophysiology of IgG4-RD, but the details of these roles remain unclear. The IgG4 molecule itself is unlikely to be the primary driver of inflammation; rather, it probably downregulates the immune response. Fibrosis might be caused by activation of innate immune cells by polarized CD4(+) T cells. Glucocorticoids are the standard initial treatment for IgG4-RD, but their long-term adverse effects and the high frequency of relapse and renal damage associated with use of this treatment has prompted a search for more effective options. B-cell depletion and the targeting of plasmablasts are both promising approaches.
authors.affiliation: Nephrology Unit, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA.
authors.forename: Frank B
authors.initials: FB
authors.lastname: Cortazar
authors.affiliation: Rheumatology Unit, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA.
authors.forename: John H
authors.initials: JH
authors.lastname: Stone
mesh_terms: D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007674:Kidney Diseases / Q000097:blood / Q000175:diagnosis / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy; D010265:Paraproteinemias / Q000097:blood / Q000150:complications* / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy
chemical_list: D007074:Immunoglobulin G