Immunomodulatory effects of anti-tumor necrosis factor alpha therapy on synovium in spondylarthropathy - Histologic findings in eight patients from an open-label pilot study

Objective. To assess the effects of treatment with anti-tumor necrosis fact or alpha (anti-TNF alpha) on synovial histology in patients with spondylart hropathy (SpA) in order to confirm the effect on peripheral synovitis and t o investigate the immunologic mechanisms involved in anti-TNF alpha therapy . Methods. Patients with treatment-resistant SpA were treated with infliximab (5 mg/kg) at weeks 0, 2, and 6 in an open-label pilot study. In 8 patients , synovial biopsy tissues obtained at baseline, week 2, and week 12 were us ed for histologic and immunohistochemical evaluation. Results. In all 8 patients (3 with ankylosing spondylitis, 1 with undiffere ntiated SpA, and 4 with psoriatic arthritis), there was a clear clinical im provement in the peripheral arthritis after anti-TNF alpha therapy. Histolo gic analysis of the synovial biopsy tissues indicated that the synovial lin ing layer thickness tended to decrease, with a significant reduction of CD5 5+ synoviocytes, at week 12. in the sublining layer, vascularity was reduce d at week 12, with a decreased endothelial expression of vascular cell adhe sion molecule 1 but not intercellular adhesion molecule 1, platelet endothe lial cell adhesion molecule I, and E-selectin. Although at week 2 and week 12, the number of neutrophils and CD68+ macrophages in the sublining layer was decreased, the overall degree of inflammatory infiltration remained unc hanged. This could be related to the lymphocyte infiltration since at week 12, only CD4+ cells (but not CD3+, CD45RO+, and CD8+ cells) tended to decre ase, while CD20+ lymphocytes and plasma cells were clearly increased. Conclusion. The reduction in lining layer thickness, vascularity, and infil tration with neutrophils and macrophages paralleled the beneficial effect o f anti-TNF alpha therapy on peripheral synovitis in 8 patients with differe nt subtypes of SpA. The adhesion molecule expression, T cell infiltration, and, most important, B cell infiltration seemed to contrast,vith previous o bservations in RA. Although these preliminary data need to be confirmed in a larger cohort, they suggest distinct immunomodulatory mechanisms of anti- TNF alpha in SpA.