title: IgG4-related disease: pathophysiologic insights drive emerging treatment approaches.
abstract: IgG4-related disease (IgG4-RD) is a fibroinflammatory condition that can affect essentially any organ. The disease shows similar histopathology findings across organ systems, consisting of a lymphoplasmacytic infiltrate enriched in IgG4-positive plasma cells, storiform fibrosis, and obliterative phlebitis. IgG4 itself appears to be a reactive phenomenon rather than the primary disease driver. Recent investigations have focused on the interactions between cells of the B cell lineage and a novel CD4+ SLAMF7+ cytotoxic T cells capable of promoting fibrosis. Plasmablasts appear to play a crucial role along with B cells in the presentation of antigen to this T cell. IgG4-RD is marked by responsiveness to glucocorticoids, but frequent disease relapse, the inability to taper glucocorticoids completely, and steroid toxicity are problematic. Targeted treatment approaches against the B cell lineage appear promising, and therapeutic efforts focused upon the CD4+ SLAMF7+ cytotoxic T cell may also be feasible.
authors: Rheumatology Clinic/Yawkey 2, Massachusetts General Hospital, Boston, USA. jhstone@partners.org.
authors: John H
authors: JH
authors: Stone
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D005938:Glucocorticoids / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D058990:Molecular Targeted Therapy; D015398:Signal Transduction; D000071176:Signaling Lymphocytic Activation Molecule Family / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D007074:Immunoglobulin G; C448987:SLAMF7 protein, human; D000071176:Signaling Lymphocytic Activation Molecule Family