Interleukin 15 Levels in Serum May Predict a Severe Disease Course in Patients with Early Arthritis

BackgroundInterleukin-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 ResultsData 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 ConclusionsPatients 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.研究背景 白细胞介素-15（Interleukin-15，IL-15）被认为参与类风湿关节炎（Rheumatoid Arthritis，RA）的病理生理机制，可在类风湿关节炎患者的血清及炎性关节滑膜液中检出，但无法在骨关节炎或其他炎性关节病患者体内检测到。因此本研究旨在分析血清IL-15（serum IL-15，sIL-15）水平能否作为早期关节炎（Early Arthritis，EA）患者疾病严重程度的生物标志物。 方法与结果 本研究对早期关节炎登记队列中的190例患者数据进行分析（女性占比77.2%，中位年龄53岁，入组时疾病中位病程为6个月）。系统记录了患者的临床及治疗信息，尤其关注改善病情抗风湿药（Disease Modifying Anti-Rheumatic Drugs，DMARDs）的处方情况。本研究采用两种不同因变量开展多变量纵向分析：1）疾病活动度评分28（Disease Activity Score 28，DAS28）；2）反映强化治疗情况的变量。两项分析均将sIL-15作为预测变量，并纳入其他与疾病严重程度相关的变量，包括类风湿因子（Rheumatoid Factor，RF）及抗环瓜氨酸肽抗体（Anti-Cyclic Citrullinated Peptide Antibodies，ACPA）。在完成随访的171例患者（共分析638次随访数据）中，71%被确诊为类风湿关节炎，29%被归类为未分化关节炎。该队列中29%的患者血清sIL-15水平升高，且该生物标志物与RF、ACPA并无广泛重叠。高血清sIL-15水平（β系数[95%置信区间]：0.12 [0.06–0.18]；P值）。 研究结论 基线血清sIL-15水平升高的早期关节炎患者，其疾病严重程度更高且需接受更强化的治疗。因此，sIL-15或可作为候选患者接受早期强化治疗的生物标志物。