抄録
Objective: The aim of this study was to characterize the histological and immunohistochemical properties of the synovial tissue and the biological properties of cultured synovial cells of rheumatoid arthritis (RA) patients undergoing treatment with biologics.
Methods: Samples of synovial tissue were taken from 15 RA patients who underwent surgery of the knee joint (8), hip joint (5), and ankle joint (2). Biologics were administered to these patients (infliximab, n=7; etanercept, n=5; tocilizumab, n=3); five RA patients who were given no such agents were used as the control group. The histopathological findings were evaluated using the histological scoring system reported by Rooney, and the relationship between the histological findings and the clinical features evaluated using the disease activity score (DAS) 28-ESR were investigated. The cultured synovial cells from the surgical specimen were analyzed for the expression levels of cytokines, chemokines, and growth factors by using the suspension array system. We also examined the immunohistochemical localization of each factor.
Results: Total Rooney's inflammation scores were significantly different in the biologics and non-biologics groups, and also in the scores for synoviocyte hyperplasia, blood vessel proliferation, perivascular infiltrates of lymphocytes, and focal aggregates of lymphocytes. Clinically, patients with high DAS28-ESR scores also had high scores in Rooney's evaluation. In cultured synovial tissue, suspension array evaluation showed that the expression of interleukin-6 (IL-6), IL-8, IL-9, IL-15, IL-17, granulocyte colony-stimulating factor, monocyte chemoattractant protein-1, and tumor necrosis factor-alpha were significant. Immunohistochemical examination revealed that these cytokines or growth factors were positive in the macrophages or lymphocytes beside the blood vessels.
Conclusion: We believe that treatment with biologics mediated the reduction of synovial tissue, especially the reduction in synovial cell proliferation in the lining layer, and the reduction of lymphocyte infiltration around the blood vessel formations by suppressing the expression of cytokines or growth factors.
