El-Gabalawy Hani S, Robinson David B, Smolik Irene, Hart Donna, Elias Brenda, Wong Keng, Peschken Christine A, Hitchon Carol A, Li Xuan, Bernstein Charles N, Newkirk Marianna M, Fritzler Marvin J
University of Manitoba, Winnipeg, Manitoba, Canada.
Arthritis Rheum. 2012 Jun;64(6):1720-9. doi: 10.1002/art.34449. Epub 2012 Feb 21.
Rheumatoid arthritis (RA) is prevalent in North American Native populations, with a high frequency of multicase families and seropositivity in first-degree relatives. This study was undertaken to determine whether the serum cytokine profile of first-degree relatives of North American Native patients with RA differed from that of individuals with no family history of autoimmunity and whether there was an association with RA autoantibodies.
North American Native patients with RA (n = 105), their first-degree relatives (n = 273), healthy North American Native controls (n = 200), and Caucasian controls (n = 150) were studied. Serum levels of 42 cytokines were tested using a multiplex laser bead assay. Rheumatoid factor (RF), anti-cyclic citrullinated peptide 2 (anti-CCP-2), monocyte chemotactic protein 1 (MCP-l), and high-sensitivity C-reactive protein (hsCRP) were tested by enzyme-linked immunosorbent assay, and HLA-DRB1 alleles by specific primers. Discriminant analysis and logistic regression classified individuals based on their cytokine profile.
The prevalence of RF (cutoff level predetermined to include 5% of Caucasian controls) and anti-CCP (cutoff level of ≥40 units) was, respectively, 88% and 81% in the RA patients, 34% and 9% in first-degree relatives, and 9% and 4% in North American Native controls; the prevalence of anti-CCP was 0% in Caucasian controls. Levels of most cytokines were highest in RA patients; 17 of 40 cytokines (43%) were significantly higher in first-degree relatives than in controls, including multiple proinflammatory cytokines. Discriminant analysis showed a notable distinction between the groups, with 85% classification accuracy. First-degree relatives had markedly higher MCP-1 and hsCRP levels than North American Native controls, but there was no consistent association with RA autoantibodies.
Our findings indicate that levels of multiple cytokines and hsCRP are higher in first-degree relatives of North American Native patients with RA compared to individuals from a nonautoimmune background. These data suggest that elevated baseline cytokine levels may be part of the risk profile for developing RA.
类风湿关节炎（RA）在北美原住民人群中普遍存在，多病例家族及一级亲属血清阳性率较高。本研究旨在确定北美原住民RA患者的一级亲属血清细胞因子谱是否与无自身免疫家族史个体不同，以及是否与RA自身抗体存在关联。
对北美原住民RA患者（n = 105）、其一级亲属（n = 273）、健康北美原住民对照（n = 200）和白种人对照（n = 150）进行研究。使用多重激光珠分析法检测42种细胞因子的血清水平。通过酶联免疫吸附测定法检测类风湿因子（RF）、抗环瓜氨酸肽2（抗CCP-2）、单核细胞趋化蛋白1（MCP-1）和高敏C反应蛋白（hsCRP），并通过特异性引物检测HLA-DRB1等位基因。判别分析和逻辑回归根据个体的细胞因子谱对其进行分类。
RA患者中RF（预先设定的截断水平包括5%的白种人对照）和抗CCP（截断水平≥40单位）的患病率分别为88%和81%，一级亲属中分别为34%和9%，北美原住民对照中分别为9%和4%；白种人对照中抗CCP的患病率为0%。大多数细胞因子水平在RA患者中最高；40种细胞因子中有17种（43%）在一级亲属中显著高于对照组，包括多种促炎细胞因子。判别分析显示各组之间有显著差异，分类准确率为85%。一级亲属的MCP-1和hsCRP水平明显高于北美原住民对照，但与RA自身抗体无一致关联。
我们的研究结果表明，与非自身免疫背景个体相比，北美原住民RA患者的一级亲属中多种细胞因子和hsCRP水平更高。这些数据表明，基线细胞因子水平升高可能是发生RA风险特征的一部分。
