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Apoptosis, loss of B-cell tolerance and lymphoid neogenesis in Sjögren's syndrome

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Background

Sjögren's syndrome is a chronic autoimmune and rheumatic disorder of the mucous membranes caused by lack of proper exocrine secretions, with prominent sicca complaints. The molecular mechanisms of the pathogenesis are virtually unknown.

Objectives

To investigate functional properties of lymphoid aggregates and its surroundings observed in salivary glands of patients with Sjögren's syndrome and in in vitro systems combined with serological analysis of blood and saliva.

Methods

Biopsy material from 178 inflamed minor salivary gland biopsies formed the basis for studies of lymphoid neogenesis. Cell surface markers, proliferation markers, adhesion molecules, chemokines, B-cell activating factor (BAFF) and local production of autoantibodies were investigated by immunohistochemistry, ELISPOT, ELISA and apoptosis determination.

Results

About every sixth biopsy contained lymphoid aggregations with germinal center-like morphology. Elevation of autoantibody production was observed related to inflamed salivary glands. Germinal center-positive patients had high expression of the lymphocyte-homing and retention chemokines and adhesion molecules. Induced apoptosis disclosed subcellular redistribution and cell surface exposure of autoantigens of high relevance for Sjögren's syndrome. Attenuated apoptosis was detected among BAFF+ B cells.

Conclusions

Ectopic secondary lymphoid follicles in Sjögren's syndrome contain all elements of relevance for driving an autoimmune response. BAFF seems to direct the lifespan of infiltrating B cells by enhancing their proliferation and maturation.

Altogether, the studies have shed light on factors involved in directing lymphocytes into inflamed tissue and maintaining inflammation in Sjögren's syndrome.

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Jonsson, R. Apoptosis, loss of B-cell tolerance and lymphoid neogenesis in Sjögren's syndrome. Arthritis Res Ther 5, 161 (2003) doi:10.1186/ar962

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Keywords

  • Salivary Gland
  • Lymphoid Follicle
  • Minor Salivary Gland
  • Autoantibody Production
  • Rheumatic Disorder