Tak P P, Spaeny-Dekking L, Kraan M C, Breedveld F C, Froelich C J, Hack C E
Department of Rheumatology, Leiden University Medical Centre, Leiden, The Netherlands.
Clin Exp Immunol. 1999 May;116(2):366-70. doi: 10.1046/j.1365-2249.1999.00881.x.
Cytotoxic cells possess specialized granules which contain perforin and a group of serine proteinases termed granzymes. Granzyme-positive cells have been identified in synovial fluid and tissue of patients with RA, where they may play an important role as mediators of granule-mediated apoptosis, extracellular proteolysis, and cytokine induction. The aim here was to define further the involvement of cytotoxic cells in RA. Plasma and synovial fluid samples from the knee joint were obtained from 31 RA patients. The disease controls included 20 osteoarthritis (OA) patients and 10 reactive arthritis (ReA) patients. A recently developed capture ELISA was used to detect soluble granzymes A and B in all patients. Compared with OA and ReA disease controls, markedly increased levels of soluble granzymes A and B were detected in both plasma and synovial fluid of RA patients (P < 0.00001). When values for soluble granzymes A and B in plasma and synovial fluid were used simultaneously as independent variables, logistic regression analysis indicated that a diagnosis of RA could be predicted correctly in 84% of the RA patients and a diagnosis of non-RA in 90% of the controls. The markedly elevated levels of soluble granzymes A and B in plasma and synovial fluid of RA patients strongly suggest that cytotoxic cells are active participants in the pathogenesis of RA. Moreover, the results suggest that measurement of granzymes may assist the laboratory evaluation of patients with arthritis. Larger studies in patients with early disease may clarify the role of this test system in differential diagnosis.
细胞毒性细胞拥有特殊的颗粒，其中含有穿孔素和一组称为颗粒酶的丝氨酸蛋白酶。在类风湿关节炎（RA）患者的滑液和组织中已鉴定出颗粒酶阳性细胞，它们可能作为颗粒介导的细胞凋亡、细胞外蛋白水解和细胞因子诱导的介质发挥重要作用。本文的目的是进一步明确细胞毒性细胞在RA中的作用。从31例RA患者获取膝关节的血浆和滑液样本。疾病对照组包括20例骨关节炎（OA）患者和10例反应性关节炎（ReA）患者。使用一种最近开发的捕获酶联免疫吸附测定法（ELISA）检测所有患者的可溶性颗粒酶A和B。与OA和ReA疾病对照组相比，在RA患者的血浆和滑液中均检测到可溶性颗粒酶A和B的水平显著升高（P < 0.00001）。当将血浆和滑液中可溶性颗粒酶A和B的值同时作为自变量时，逻辑回归分析表明，84%的RA患者能够被正确诊断为RA，90%的对照组能够被正确诊断为非RA。RA患者血浆和滑液中可溶性颗粒酶A和B水平的显著升高强烈表明细胞毒性细胞是RA发病机制中的积极参与者。此外，结果表明颗粒酶的检测可能有助于关节炎患者的实验室评估。对早期疾病患者进行更大规模的研究可能会阐明该检测系统在鉴别诊断中的作用。
