Livshits Gregory, Zhai Guangju, Hart Deborah J, Kato Bernet S, Wang Huizhong, Williams Frances M K, Spector Tim D
King's College London, London, UK.
Arthritis Rheum. 2009 Jul;60(7):2037-45. doi: 10.1002/art.24598.
There is a great need for identification of biomarkers that could improve the prediction of early osteoarthritis (OA). We undertook this study to determine whether circulating levels of interleukin-6 (IL-6), tumor necrosis factor alpha (TNFalpha), and C-reactive protein (CRP) can serve as useful markers of radiographic knee OA (RKOA) in a normal human population.
RKOA data were obtained from the cohort of the Chingford Study, a prospective population-based study of healthy, middle-aged British women. The RKOA-affected status of the subjects was assessed using the Kellgren/Lawrence (K/L) grade as determined on radiographs obtained at baseline (n = 908) and at 10 years and 15 years thereafter. Serum levels of CRP, IL-6, and TNFalpha were assayed at 5, 8, and 15 years, using high-sensitivity commercial assays. A K/L grade of >or=2 in either knee was used as the outcome measure. Statistical analyses included analysis of variance for repeated measurements and logistic regression models, together with longitudinal modeling of dichotomous responses.
During 15 years of followup, the prevalence of RKOA (K/L grade >or=2) increased from 14.7% to 48.7% (P < 0.00001 versus baseline). The body mass index (BMI) and circulating levels of CRP and IL-6 were consistently and significantly higher in subjects diagnosed as having RKOA. When multiple logistic regression was applied to the data, the variables of older age (P = 3.93 x 10(-5)), higher BMI at baseline (P = 0.0003), and increased levels of IL-6 at year 5 (P = 0.0129) were determined to be independent predictors of the appearance of RKOA at year 10. The results were fully confirmed using longitudinal modeling of repeated measurements of the data obtained at 3 visits. The odds ratio for RKOA in subjects whose IL-6 levels were in the fourth quartile of increasing levels (versus the first quartile) was 2.74 (95% confidence interval 1.94-3.87).
This followup study showed that individuals were more likely to be diagnosed as having RKOA if they had a higher BMI and increased circulating levels of IL-6. These results should stimulate more work on IL-6 as a potential therapeutic target.
迫切需要鉴定能够改善早期骨关节炎（OA）预测的生物标志物。我们开展这项研究，以确定白细胞介素-6（IL-6）、肿瘤坏死因子α（TNFα）和C反应蛋白（CRP）的循环水平是否可作为正常人群中膝关节X线骨关节炎（RKOA）的有用标志物。
RKOA数据来自Chingford研究队列，这是一项基于人群的前瞻性研究，研究对象为健康的英国中年女性。使用Kellgren/Lawrence（K/L）分级评估受试者的RKOA患病状况，该分级根据基线（n = 908）以及此后10年和15年获得的X线片确定。在第5年、第8年和第15年使用高灵敏度商业检测法测定血清CRP、IL-6和TNFα水平。以任一膝关节的K/L分级≥2作为结局指标。统计分析包括重复测量的方差分析和逻辑回归模型，以及二分反应的纵向建模。
在15年的随访期间，RKOA（K/L分级≥2）的患病率从14.7%增至48.7%（与基线相比，P < 0.00001）。被诊断为患有RKOA的受试者的体重指数（BMI）以及CRP和IL-6的循环水平始终显著更高。对数据进行多因素逻辑回归分析时，年龄较大（P = 3.93×10⁻⁵）、基线时BMI较高（P = 0.0003）以及第5年IL-6水平升高（P = 0.0129）被确定为第10年出现RKOA的独立预测因素。使用对3次访视获得的数据进行重复测量的纵向建模，完全证实了上述结果。IL-6水平处于升高水平第四四分位数（与第一四分位数相比）的受试者患RKOA的比值比为2.74（95%置信区间1.94 - 3.87）。
这项随访研究表明，BMI较高且IL-6循环水平升高的个体更有可能被诊断为患有RKOA。这些结果应促使人们针对IL-6作为潜在治疗靶点开展更多研究。
