Synovial Fibroblast Hyperplasia in Rheumatoid Arthritis Clinicopathologic Correlations and Partial Reversal by Anti-Tumor Necrosis Factor Therapy
Synovial Fibroblast Hyperplasia in Rheumatoid Arthritis Clinicopathologic Correlations and Partial Reversal by Anti-Tumor Necrosis Factor Therapy
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DOI：
10.1002/art.30433
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发表时间：
2011-09-01
影响因子：
--
通讯作者：
Pablos, Jose L.
中科院分区：
文献类型：
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作者：
Izquierdo, Elena;Canete, Juan D.;Pablos, Jose L.
客观的。滑膜成纤维细胞（SF）增生导致类风湿性关节炎（RA）的发病机制，但有关这一过程的定量信息很少。本研究旨在评估成纤维细胞特异性标记物 Hsp47 作为 SF 的定量标记物，并分析其临床病理相关性和抗肿瘤坏死因子 α（抗 TNF α）治疗后的演变。方法。滑膜活检样本取自 48 名 RA 患者和 20 名健康或患有骨关节炎 (OA) 的对照者。 25 名在活检时患有活动性疾病的 RA 患者在抗 TNF α 治疗后接受了第二次活检。对 Hsp47、炎症细胞和血管细胞标记物进行免疫标记。对 Hsp47 阳性衬层和亚衬层分数面积进行量化，并分析它们与临床病理变量的相关性。结果。在正常和患病的滑膜组织中，Hsp47 由内膜、内膜下和血管周围成纤维细胞特异性且均匀地表达。与正常组织相比，RA 和晚期 OA 组织的衬里 SF 面积均显着增加。与正常组织相比，RA 组织中的衬里 SF 面积增加，但晚期 OA 组织中没有增加。内层 SF 面积与巨噬细胞密度、28 个关节的疾病活动评分以及 RA 病程呈正相关。相反，下层 SF 面积与 RA 疾病持续时间和活动度呈负相关。抗TNFα治疗后观察到衬里SF面积显着减少，但衬里SF面积没有显着减少。结论。我们的研究结果表明，Hsp47 是量化人类滑膜组织中 SF 的可靠标记。我们的数据表明，内层和下层 SF 在疾病过程中经历不同的动态。内层 SF 扩张与 RA 的活动和时间进展平行，并且可以通过抗 TNF α 治疗部分逆转。
Objective. Synovial fibroblast (SF) hyperplasia contributes to the pathogenesis of rheumatoid arthritis (RA), but quantitative information on this process is scarce. This study was undertaken to evaluate the fibroblast-specific marker Hsp47 as a quantitative marker for SFs and to analyze its clinicopathologic correlates and evolution after anti-tumor necrosis factor alpha (anti-TNF alpha) therapy.Methods. Synovial biopsy samples were obtained from 48 patients with RA and 20 controls who were healthy or had osteoarthritis (OA). Twenty-five RA patients who had active disease at the time of biopsy underwent a second biopsy after anti-TNF alpha therapy. Immunolabeling for Hsp47, inflammatory cells, and vascular cell markers was performed. Hsp47-positive lining and sublining fractional areas were quantified, and their correlation with clinicopathologic variables was analyzed.Results. In normal and diseased synovial tissue, Hsp47 was specifically and uniformly expressed by lining, sublining, and perivascular fibroblasts. Lining SF area was significantly increased in both RA and late OA tissue compared to normal tissue. Sublining SF area was increased in RA tissue but not in late OA tissue compared to normal tissue. Lining SF area was positively correlated with macrophage density, Disease Activity Score in 28 joints, and RA disease duration. In contrast, sublining SF area was negatively correlated with RA disease duration and activity. A significant reduction in lining SF area but not sublining SF area was observed after anti-TNF alpha therapy.Conclusion. Our findings indicate that Hsp47 is a reliable marker for quantifying SFs in human synovial tissue. Our data suggest that lining and sublining SFs undergo different dynamics during the course of the disease. Lining SF expansion parallels the activity and temporal progression of RA and can be partially reversed by anti-TNF alpha therapy.