Alefacept treatment in psoriatic arthritis - Reduction of the effector T cell population in peripheral blood and synovial tissue is associated with improvement of clinical signs of arthritis
Alefacept treatment in psoriatic arthritis - Reduction of the effector T cell population in peripheral blood and synovial tissue is associated with improvement of clinical signs of arthritis
复制标题
DOI：
10.1002/art.10543
复制
发表时间：
2002-10-01
影响因子：
--
通讯作者：
Tak, PP
中科院分区：
文献类型：
--
作者：
Kraan, MC;van Kuijk, AWR;Tak, PP
目标。探讨alfacept（一种完全人淋巴细胞功能相关抗原3 [LFA-3]/IgG1融合蛋白，阻断LFA-3/CD2相互作用）是否能够减轻活动性银屑病关节炎（PsA）患者关节炎症的体征和症状。在一项开放标签和探索性研究中，11名活动性PsA患者接受了阿法西普治疗12周。在基线和治疗4、9、12和16周后进行临床联合评估和实验室评估。在基线和治疗4周和12周后，通过关节镜获得炎症指数关节（膝关节、踝关节、腕关节或掌指关节）的一系列滑膜组织（ST）活检标本。在治疗结束时，11例患者中有6例（55%）达到了疾病活动评分（DAS）反应标准。9名患者（82%）在研究期间的任何时候都达到了DAS反应标准。治疗12周后，ST区CD4+淋巴细胞（P < 0.05）、CD8+淋巴细胞（P = 0.05）、CD68+巨翼细胞（P < 0.02）较基线有统计学意义。满足DAS反应标准的患者的ST和外周血在基线时含有更多的CD45RO+细胞，并且与无反应的患者相比，这些细胞明显减少。alfacept治疗后ST的改变以及临床关节评分的改善支持了T细胞活化在这种慢性炎症性疾病中起重要作用的假设。此外，由于alfacept（一种T细胞特异性药物）导致巨噬细胞浸润减少，数据表明T细胞高度参与PsA滑膜炎症。
Objective. To investigate whether alefacept (a fully human lymphocyte function-associated antigen 3 [LFA-3]/IgG1 fusion protein that blocks the LFA-3/CD2 interaction) is able to reduce the signs and symptoms of joint inflammation in patients with active psoriatic arthritis (PsA).Methods. Eleven patients with active PsA were treated with alefacept for 12 weeks in an open-label and explorative study. Clinical joint assessment and laboratory assessments were performed at baseline and after 4, 9, 12, and 16 weeks of treatment. Serial synovial tissue (ST) biopsy specimens from an inflamed index joint (knee, ankle, wrist, or metacarpophalangeal joint) were obtained by arthroscopy at baseline and after 4 and 12 weeks of treatment.Results. At the completion of treatment, 6 of 11 patients (55%) fulfilled the Disease Activity Score (DAS) response criteria. Nine patients (82%) fulfilled the DAS response criteria at any point during the study. There was a statistically significant reduction in CD4+ lymphocytes (P < 0.05), CD8+ lymphocytes (P = 0.05), and CD68+ macropliages (P < 0.02) in the ST after 12 weeks of treatment compared with baseline. The ST and peripheral blood of those patients fulfilling the DAS response criteria contained more CD45RO+ cells at baseline and displayed a significant reduction in these cells compared with nonresponding patients.Conclusion. The changes in ST, together with the improvement in clinical joint scores, after treatment with alefacept support the hypothesis that T cell activation plays an important role in this chronic inflammatory disease. Furthermore, since alefacept, a T cell-specific agent, led to decreased macrophage infiltration, the data indicate that T cells are highly involved in synovial inflammation in PsA.