Interleukin 10 and Tumor Necrosis Factor-α Genotypes in Rheumatoid Arthritis - Association with Clinical Response to Glucocorticoids
Interleukin 10 and Tumor Necrosis Factor-α Genotypes in Rheumatoid Arthritis - Association with Clinical Response to Glucocorticoids
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DOI：
10.3899/jrheum.090566
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发表时间：
2010-03-01
影响因子：
3.9
通讯作者：
Suarez, Ana
中科院分区：
文献类型：
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作者：
de Paz, Banesa;Alperi-Lopez, Mercedes;Suarez, Ana
目标。类风湿关节炎（RA）中存在白细胞介素10 （IL-10）和肿瘤坏死因子α (tnf - α)水平失调，它们在疾病中的作用尚存争议。我们分析了IL-10和tnf - α的功能多态性与诊断时的易感性和疾病特征的关系，并评估了它们作为临床治疗反应预测因子的可能性。新近发病的RA患者（n = 162）和健康对照（n = 373）被分型为-1082个IL-10和-308个tnf - α多态性，数据与诊断时患者的临床和免疫学测量相关。通过疾病活动评分（DAS28）的绝对变化和美国风湿病学会的改善标准来确定125例患者6个月后对治疗的反应。我们发现，与对照组相比，RA患者中IL-10低制造者基因型（-1082AA）的频率降低（26.5% vs 38.9%; p = 0.006），而这是抗环瓜氨酸肽抗体（anti-CCP）阳性的危险因素（p = 0.028）。对治疗的临床反应评估表明，携带高IL-10基因型与良好的结果相关（p = 0.009）。特别是对强的松治疗（p = 0.0003）。单独使用tnf - α多态性未观察到显著影响；然而，与IL-10基因型联合使用，则增加了这些相关性的强度。结果显示低IL-10产生基因型与RA的保护作用相关；然而，当其他特定的遗传和/或环境因素触发RA发病时，该基因型可能倾向于抗ccp + RA疾病的发展，并且对强的松治疗的反应降低。（首次发布2010年1月15日；J Rheumatol 2010;37:503-11; doi: 10.3899/ jrheumat. 090566）
Objective. There are dysregulated levels of interleukin 10 (IL-10) and tumor necrosis factor-alpha (TNF-alpha) in rheumatoid arthritis (RA), and their role in (lie disease is controversial. We analyzed the association of functional polymorphisms of IL-10 and TNF-alpha with susceptibility and disease characteristics at the time of diagnosis, and we also evaluated their possible use as predictors of clinical response to treatments.Methods. Patients with recent-onset RA (n = 162) and healthy controls (n = 373) were genotyped for -1082 IL-10 and -308 TNF-alpha polymorphisms and data were related to clinical and immnunological measurements of patients at the time of diagnosis. Response to treatment after 6 months was determined in 125 patients by the absolute change in Disease Activity Score (DAS28) and the American College of Rheumatology criteria for improvement.Results. We found a reduced frequency of the low IL-10 producer genotype (-1082AA) in patients with RA compared to controls (26.5% vs 38.9%; p = 0.006), while it is a risk factor for anticyclic citrullinated peptide antibodies (anti-CCP) positivity (p = 0.028). Evaluation of clinical response to treatments indicated that carriage of the high IL-10 genotype was associated with a favorable outcome (p = 0.009). specifically to prednisone therapy (p = 0.0003). No significant effects were observed with TNF-alpha polymorphism alone; however, in combination with the IL-10 genotype, it increased the strength of these associations.Conclusion. Results show an association between the low IL-10 producer genotype and protection from RA; nevertheless, when other specific genetic and/or environmental factors trigger onset of RA, this genotype may predispose to development of anti-CCP+ RA disease with reduced response to prednisone treatment. (First Release Jan 15 2010; J Rheumatol 2010;37:503-11; doi: 10.3899/jrheum.090566)