BCA-1 (CXCL13) and SLC (CCL21) production and lymphoid neogenesis in rheumatoid synovitis

Objective

To relate the production of BCA-1 and SLC to lymphoid neogenesis in the rheumatoid arthritis (RA) synovium, in order to analyse their expression in relationship to the development of lymphoid features (T/B cell segregation, follicular dendritic cells [FDC] and expression of peripheral node addressin [PNAd]).

Methods

Fifty synovial-membrane samples from 20 RA patients were studied using immunohystochemistry and in situ hybridization. Samples were stained for T, B and FDC, PNAd, BCA-1 and SLC. In situ hybridisation was performed for BCA-1 and SLC. Grading analysis was assessed according to the radial cell count from the central blood vessel to the point of widest infiltration: grade 1 (2–5 cells), grade 2 (6–10) and grade 3 (>10). The percentage of aggregates positive for each factor within each grading group was calculated.

Results

Samples from 17 patients showed the presence of grade 2 and/or 3 aggregates; in three cases only perivascular cuffing was demonstrated. Fully formed follicular-like structures, with centrally located CD21⁺ FDC and T/B segregation, were seen in 7 of the 20 patients (35%). BCA-1 and SLC were expressed within lymphocytic clusters in 18 of 20 and 15 of 20 patients, respectively. BCA-1 and SLC expression was associated with mature follicular organisations. However they were detected also in the absence of fully formed lymphoid-like structures. Production of BCA-1 and SLC was established by in situ hybridisation to localize within lymphocytic clusters but even in the absence of mature follicles.

Conclusions

This study confirms that the expression of BCA-1 and SLC is associated with the ectopic lymphoid organisation seen in RA. Furthermore, it demonstrates by in situ hybridisation the precise site of production of these chemokines. Finally, grading analysis indicates a relationship between their expression and the progressive enlargement and organisation of infiltrating cell.