Ectopic lymphoid neogenesis in psoriatic arthritis

Abstract

Background: Ectopic lymphoid neogenesis (LN) occurs in rheumatoid synovium, where it is thought to drive local antigen-dependent B cell development and autoantibody production. This process involves the expression of specific homing chemokines and the development of high endothelial venules (HEV). Objective: To investigate whether these mechanisms occur in psoriatic arthritis (PsA) synovium, where autoantibodies have not been described and the organisation and function of B cells is not clear, and to analyse their clinical correlates. Methods: Arthroscopic synovial biopsy specimens from patients with PsA before and after tumour necrosis factor a blockade were characterised by immunohistochemical analysis for T/B cell segregation, peripheral lymph node addressin (PNAd)-positive HEV, and the expression of CXCL13, CCL21 and CXCL12 chemokines in relation to the size of lymphoid aggregates. Results: Lymphoid aggregates of variable sizes were observed in 25 of 27 PsA synovial tissues. T/B cell segregation was often observed, and was correlated with the size of lymphoid aggregates. A close relationship between the presence of large and highly organised aggregates, the development of PNAd+ HEV, and the expression of CXCL13 and CCL21 was found. Large organised aggregates with all LN features were found in 13 of 27 tissues. LN in PsA synovitis was not related to the duration, pattern or severity of the disease. The synovial LN pattern remained stable over time in persistent synovitis, but a complete response to treatment was associated with a regression of the LN features. Conclusions: LN occurs frequently in inflamed PsA synovial tissues. Highly organised follicles display the characteristic features of PNAd+ HEV and CXCL13 and CCL21 expression, demonstrating that the microanatomical bases for germinal centre formation are present in PsA. The regression of LN on effective treatment indicates that the pathogenic and clinical relevance of these structures in PsA merits further investigation.

B Lymphocyte Autoimmunity in Rheumatoid Synovitis Is Independent of Ectopic Lymphoid Neogenesis

“…1B), independently of potentially confounding factors such as the MHC background (HLA-DR shared epitope) and the presence of intracellular citrullinated proteins (data not shown) (31,32). These data confirm and extend our previous observations (26,28) showing that ectopic lymphoid neogenesis in the synovial membrane is neither restricted to nor preferentially associated with autoantibody positive rheumatic conditions.…”

“…Moreover, we recently demonstrated that B cell depletion by Rituximab decreased synovial tissue infiltration as well as lymphoid neogenesis after 16 wk of treatment (48). Taken together with the coexistence of different degrees of lymphoid organization in a single sample (23,26), these data indicate that synovial lymphoid neogenesis is a dynamic process which could be related to inflammation rather than a fixed pathological feature committed to specific B cell autoantigens. In SLO, Ag-driven B cell responses require the full maturation of lymphoid structures toward GC-reactions, a complex process orchestrated by lymphoid chemokines and cytokines (49,50) Defective expression of these mediators leads to abortive follicle formation and impaired B cell responses (49,51).…”

Alterations of the synovial T cell repertoire in anti–citrullinated protein antibody–positive rheumatoid arthritis

“…Synovial tissue biopsy samples were processed and evaluated for lining layer thickness, vascularity, global inflammatory infiltration, and lymphoid aggregates, as described previously (35)(36)(37). Synovial tissues from the 158 RA patients were divided into 2 groups.…”

Increased numbers of CD5+ B lymphocytes with a regulatory phenotype in spondylarthritis

“…B cells and plasma cells are found in the involved peripheral synovium of SpA patients with peripheral synovitis (3,4) as well as in the subchondral bone marrow of patients with axial SpA (5). The B cell infiltration in SpA patients with peripheral synovitis is often organized in aggregates (6,7) and, even if germinal center-like features remain rare, can display molecular features of antigen-driven clonal B cell expansion (8,9). Besides this indirect evidence from immunopathologic studies, a direct functional role of B cells in SpA pathogenesis is suggested by the contribution of humoral immunity to versican in the induction of experimental spondylitis and sacroiliitis in BALB/c mice (10).…”