IL-17A levels in systemic lupus erythematosus associated with inflammatory markers and lower rates of malignancy and heart damage: Evidence for a dual role.
IL-17A levels in systemic lupus erythematosus associated with inflammatory markers and lower rates of malignancy and heart damage: Evidence for a dual role.
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DOI：
10.5152/eurjrheum.2017.16059
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发表时间：
2017-03
影响因子：
1.9
通讯作者：
W. Raymond;G. Ostli-Eilertsen;S. Griffiths;J. Nossent
中科院分区：
文献类型：
--
作者：
W. Raymond;G. Ostli-Eilertsen;S. Griffiths;J. Nossent
目的白细胞介素17（IL-17）家族细胞因子参与多种慢性炎症性疾病。尽管在临床研究中存在矛盾的发现和缺乏因果关系，但在强直性脊柱炎中表现出疾病改善能力后，IL-17抑制系统性红斑狼疮（SLE）作为一种潜在的治疗途径重新受到关注。我们研究了SLE患者白细胞介素17 A（IL-17 A）的临床相关性。材料与方法一项横断面研究，涉及SLE患者（n=102;年龄：49岁; 86%为女性）从区域登记处招募。通过免疫测定法测定IL-17 A水平，通过系统性红斑狼疮疾病活动指数-2K（SLEDAI-2K）测定疾病活动性，并通过系统性狼疮国际合作临床损伤指数（SDI）评分测定累积损伤。使用非参数技术来检查IL-17 A与疾病活动性之间的关联，并将自身抗体谱与健康对照（n=31）进行比较：使用主成分分析（PCA）来确定SLE患者中免疫细胞在疾病状态和损伤发展中的相互作用。结果SLE患者IgG水平较高，T细胞和B细胞计数较低，但IL-17 A水平中位数与对照组无差异（28.4 vs. 28.4 pg/mL，p=0.9）。在SLE患者中，IL-17 A与SLEDAI-2K或SDI不相关，但与年龄呈负相关（相关系数，Rs.=- 0.29，p<0.05），收缩压（Rs.=- 0.31，p<0.05），吸烟年数（Rs.=- 0.43，p<0.05），累积心脏（Rs.=- 0.22，p<0.05）和恶性损害（Rs.=- 0.18，p<0.05）。IL-17 A与免疫球蛋白G（IgG）水平存在血清学相关性（Rs.= 0.21，p<0.05）、高敏C反应蛋白（hs-CRP）水平（Rs.= 0.21，p<0.05）0.28，p<0.05），蛋白尿（Rs.= 0.28，p <0.05 0.64，p<0.05）和前白蛋白（Rs.=- 0.22，p<0.05）。纵向数据显示IL-17 A水平仅适度波动，独立于SLEDAI-2K。结论IL-17 A在参与SLE患者炎症反应的同时，可能具有一定的保护作用。
OBJECTIVE The interleukin 17 (IL-17) cytokine family is involved in a number of chronic inflammatory diseases. In spite of contradictory findings and a lack of causality in clinical studies, IL-17 inhibition for systemic lupus erythematosus (SLE) has regained attention as a potential therapeutic pathway, after demonstrating disease-modifying capabilities in ankylosing spondylitis. We investigated the clinical associations of interleukin 17 A (IL-17A) in patients with SLE. MATERIAL AND METHODS A cross-sectional study was performed involving SLE patients (n=102; age: 49 years; 86% female) recruited from a regional registry. IL-17A levels were determined by immunoassay, disease activity by Systemic Lupus Erythematosus Disease Activity Index-2K (SLEDAI-2K), and cumulative damage by Systemic Lupus International Collaborative Clinics Damage Index (SDI) scores. Non-parametric techniques were used to examine the association between IL-17A and disease activity and autoantibody profiles were compared with healthy controls (n=31): principal component analysis (PCA) was used to determine the interplay of immune cells across disease states and damage development in SLE patients. RESULTS SLE patients had higher IgG levels, lower T-cell and B-cell counts, but median IL-17A levels did not differ from the controls (28.4 vs. 28.4 pg/mL, p=0.9). In SLE patients, IL-17A did not correlate with SLEDAI-2K or SDI, but was inversely related with age (correlation coefficients, Rs.=-0.29, p<0.05), systolic blood pressure (Rs.=-0.31, p<0.05), years of smoking (Rs.=-0.43, p<0.05), cumulative heart (Rs.=-0.22, p<0.05), and malignancy damage (Rs.=-0.18, p<0.05). Serological correlations for IL-17A existed with immunoglobulin G (IgG) levels (Rs.=0.21, p<0.05), high sensitivity C-reactive protein (hs-CRP) levels (Rs.=0.28, p<0.05), proteinuria (Rs.=0.64, p<0.05), and pre-albumin (Rs.=-0.22, p<0.05). Longitudinal data showed only modest fluctuation in IL-17A levels, independent of SLEDAI-2K. CONCLUSION These results suggest that IL-17A, while participating in inflammation, may also serve a protective purpose in SLE patients.