Effects of rituximab and infliximab on carboxypeptidase B and its substrates in RA synovium
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Objective: Carboxypeptidase b (CPB) promotes coagulation and may have an anti-inflammatory role in arthritis through its ability to cleave pro-inflammatory mediators osteopontin (OPN) and complement C5a. We evaluated synovial expression of CPB, C5a and OPN at baseline and post-treatment with biologics and explored associations with clinical response. Methods: RA patients receiving infliximab (n=9) or rituximab (n=5) had a synovial biopsy at baseline and 16 weeks post therapy. Expression of CPB, C5a, OPN, the macrophage marker CD68, B-cell marker CD20 and T-cell marker CD3 was assessed using immunohistochemistry and image analysis. Two blinded investigators independently calculated expression. Clinical disease activity scores (DAS28) were obtained at baseline, the second arthroscopy, and one year. Synovial expression and associations between biomarkers with clinical activity were evaluated using non-parametric tests. Results: The patients receiving infliximab and rituximab were clinically similar. CPB staining was most intense in the synovial lining layer, around blood vessels and in some lymphocytic infiltrates. OPN and C5a staining was more diffuse throughout the synovium. At baseline, CPB expression correlated with macrophages as well as T and B lymphocytes. C5a staining correlated with B lymphocytes. Synovial expression did not correlate with baseline DAS28. At 16 weeks C5a expression correlated with DAS28 and with DAS 1 year post treatment. Conclusion: CPB expression may be linked to macrophages and B&T lymphocytes. Of these, it is likely that synovial macrophages play the greatest role in CPB expression.