Association of CXCL13 and CCL21 expression with the progressive organization of lymphoid‐like structures in Sjögren's syndrome
Open Access
- 2 June 2005
- journal article
- research article
- Published by Wiley in Arthritis & Rheumatism
- Vol. 52 (6) , 1773-1784
- https://doi.org/10.1002/art.21062
Abstract
Objective Ectopic lymphoneogenesis can occur in the salivary glands of Sjögren's syndrome (SS) patients and is associated with local antigen‐driven B cell responses, autoantibody formation, and potential lymphomatous transformation. CXCL13 and CCL21 have been identified in salivary glands, but their role in ectopic lymphoneogenesis in SS remains unclear. This study aimed to evaluate the microanatomic association between CXCL13 and CCL21 expression and the acquisition of lymphoid features in periductal foci. Methods Salivary glands from 37 SS patients and 9 chronic sialadenitis patients were analyzed by immunohistochemistry for T cell/B cell segregation, CD21+ follicular dendritic cell networks, and peripheral lymph node addressin (PNAd)–positive high endothelial venules (HEVs) in relationship to the size of the aggregates and the expression of CXCL13 and CCL21 within infiltrating cells, epithelium, and endothelium. Results Grade 1 aggregates (10–50 lymphocytes) demonstrated predominance of nonorganized CD3+ cells, while grade 2 (>50 lymphocytes) and grade 3 (>50 with germinal centers) showed a progressive increase in CD20+ B cells and T cell/B cell segregation. This higher degree of lymphoid organization was significantly related to an increased expression of CXCL13 within infiltrating cells and PNAd+ HEV–associated CCL21‐producing cells. Conversely, no association between lymphoid organization and lymphoid chemokine expression by epithelial cells was observed. Conclusion The acquisition of lymphoid features by inflammatory foci in SS is critically associated with the enlargement of the inflammatory foci and with the expression of CXCL13 and CCL21 within the infiltrate, but is not associated with their expression by epithelial cells. These data strongly support an active participation of CXCL13 and CCL21 in regulating the progressive organization and maintenance of periductal foci.Keywords
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