血清IL-15可预测早期关节炎患者的病情严重程度

血清IL-15可预测早期关节炎患者的病情严重程度

赵金霞

    摘要  背景：白介素-15（IL-15）参与类风湿关节炎的病理生理机制，RA患者血清和滑液中可以检测到IL-15，而骨关节炎和其他炎性关节疾病中则检测不到。因此，本研究的目的是分析血清IL-15（sIL-15）是否可以作为早期类风湿关节炎患者疾病活动度的生物学标志物。

     方法和结果：分析190例早期类风湿关节炎患者的资料（77.2% 为女性; 中位年龄53岁；纳入分析时的中位病程为6个月）。详细记录患者临床和治疗信息，尤其是DMARD药物的应用。依据不同的因变量进行二次多变量纵向分析：1) DAS28和 2) 反应强化治疗的变量。均将sIL-15作为预测变量，并包括其他与疾病严重程度相关的变量。包括类风湿因子、抗环瓜氨酸肽（ACPA）抗体。在完成随访的171例患者中，71%确诊为类风湿关节炎，29%为未分化关节炎。29%的患者sIL-15水平升高，该指标与RF或ACPA并无广泛的重叠。在校正了性别、年龄和治疗等混杂因素之后，高水平sIL-15 (β -系数 [95%CI]: 0.12 [0.06-0.18]; p<0.001) 或 ACPA (0.34[0.01-0.67]; p = 0.044) 均与高DAS28评分显著且独立相关。此外，sIL-15水平升高的患者接受强化治疗的危险性显著升高(RR 1.78, 95% CI 1.18-2.7; p = 0.007).

    结论：基线时sIL-15水平升高的早期类风湿关节炎患者病情更严重，且接受更强化的治疗措施。因此，sIL-15可能作为患者需要接受早期且更积极治疗的生物学标志物。

     附原文：BACKGROUND: Interleukin-15 (IL-15) is thought to be involved in the physiopathological mechanisms of RA and it can be detected in the serum and the synovial fluid of inflamed joints in patients with RA but not in patients with osteoarthritis or other inflammatory joint diseases. Therefore, the objective of  this work is to analyse whether serum IL-15 (sIL-15) levels serve as a biomarker of disease severity in patients with early arthritis (EA). METHODOLOGY AND RESULTS: Data from 190 patients in an EA register were analysed (77.2% female; median age 53 years; 6-month median disease duration at entry). Clinical and treatment information was recorded systematically, especially the prescription of disease modifying anti-rheumatic drugs. Two multivariate longitudinal analyses were performed with different dependent variables: 1) DAS28 and 2) a variable reflecting intensive treatment. Both included sIL-15 as predictive variable and other variables associated with disease severity, including rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (ACPA). Of the 171 patients (638 visits analysed) completing the follow-up, 71% suffered rheumatoid arthritis and 29% were considered as undifferentiated arthritis. Elevated sIL-15 was detected in 29% of this population and this biomarker did not overlap extensively with RF or ACPA. High sIL-15 levels (β Coefficient [95% confidence interval]: 0.12 [0.06-0.18]; p<0.001) or ACPA (0.34 [0.01-0.67]; p = 0.044) were significantly and independently associated with a higher DAS28 during follow-up, after adjusting for confounding variables such as gender, age and treatment. In addition, those patients with elevated sIL-15 had a significantly higher risk of receiving intensive treatment (RR 1.78, 95% confidence interval 1.18-2.7; p = 0.007). CONCLUSIONS: Patients with EA displaying high baseline sIL-15 suffered a more severe disease and received more intensive treatment. Thus, sIL-15 may be a biomarker for patients that are candidates for early and more intensive treatment.

    引自: González-Álvaro I, Ortiz AM, Alvaro-Gracia JM, et al. Interleukin 15 levels in serum may predict a severe disease course in patients with early arthritis. PLoS One. 2011;6(12):e29492. Epub 2011 Dec 29.