IgG4-Related Sclerosing Disease, an Emerging Entity: A Review of a Multi-System Disease

Abstract

Immunoglobulin G4-related systemic disease (IgG4-RSD) is a recently defined emerging entity characterized by a diffuse or mass forming inflammatory reaction rich in IgG4-positive plasma cells associated with fibrosclerosis and obliterative phlebitis. IgG4-RSD usually affects middle aged and elderly patients, with a male predominance. It is associated with an elevated serum titer of IgG4, which acts as a marker for this recently characterized entity. The prototype is IgG4-related sclerosing pancreatitis or autoimmune pancreatitis (AIP). Other common sites of involvement are the hepatobiliary tract, salivary gland, orbit, and lymph node, however practically any organ can be involved, including upper aerodigestive tract, lung, aorta, mediastinum, retroperitoneum, soft tissue, skin, central nervous system, breast, kidney, and prostate. Fever or constitutional symptoms usually do not comprise part of the clinical picture. Laboratory findings detected include raised serum globulin, IgG and IgG4. An association with autoantibody detection (such as antinuclear antibodies and rheumatoid factor) is seen in some cases. Steroid therapy comprises the mainstay of treatment. Disease progression with involvement of multiple organ-sites may be encountered in a subset of cases and may follow a relapsing-remitting course. The principal histopathologic findings in several extranodal sites include lymphoplasmacytic infiltration, lymphoid follicle formation, sclerosis and obliterative phlebitis, along with atrophy and destruction of tissues. Immunohistochemical staining shows increased IgG4+ cells in the involved tissues (>50 per high-power field, with IgG4/IgG ratio >40%). IgG4-RSD may potentially be rarely associated with the development of lymphoma and carcinoma. However, the nature and pathogenesis of IgG4-RSD are yet to be fully elucidated and provide immense scope for further studies.

The S228P Mutation Prevents in Vivo and in Vitro IgG4 Fab-arm Exchange as Demonstrated using a Combination of Novel Quantitative Immunoassays and Physiological Matrix Preparation

“…4), provides a buffered, physiologically relevant matrix to specifically monitor FAE of IgG4 Abs of interest in the absence of contaminating endogenous IgG4 WT molecules. The 600 g/ml of endogenous IgG4 Abs depleted from plasma by anti-IgG4 affinity chromatography is in good agreement with previous reports which state that IgG4 plasma concentrations can range from 0.1 to 1.4 mg/ml in healthy individuals (33,34). There was no significant difference in the extent of in vitro FAE in, IgG4-depleted plasma from a healthy volunteer or buffer alone (Fig.…”

Igg4-Related Disorder and Endocrine Diseases: A Review of the Literature

“…Many criteria have been developed to diagnose AIP and avoid surgery in cases that are steroid responsive [35]. These criteria include the Asian diagnostic criteria for auto-immune pancreatitis as well as the Mayo clinic diagnostic criteria (the HISORt criteria).…”

IgG4-related Hashimoto’s thyroiditis – A new variant of a well known disease

“…Laboratory testing revealed a normal hemoglobin level of 15.1 g/dL (normal, 14-18), a normal white blood cell count of 10.4 X 10 3 /µL (normal, [4][5][6][7][8][9][10][11] and an elevated platelet count of 521 X 10 3 /µL (normal, 150-450). Increased erythrocyte sedimentation rate (ESR) of 81 mm/h (normal, < 31) and C-reactive protein of 8.2 mg/dL (normal, < 1) were found, with an elevated thyroid-stimulating hormone (TSH) of 19 mIU/L (normal, 0.1-4) and a normal free thyroxine (FT 4 ) of 0.99 ng/dL (normal, 0.93-1.7).…”