Padyukov L, Lampa J, Heimbürger M, Ernestam S, Cederholm T, Lundkvist I, Andersson P, Hermansson Y, Harju A, Klareskog L, Bratt J
Unit of Rheumatology, Karolinska Hospital, Karolinska Institutet, Stockholm, Sweden.
Ann Rheum Dis. 2003 Jun;62(6):526-9. doi: 10.1136/ard.62.6.526.
Rheumatoid arthritis (RA) is a genetically complex disease where the response to different treatments varies greatly between different patients. This is the case with the tumour necrosis factor (TNF) blocking agents, where 20-40% of patients have been described as non-responders. No predictive markers exist as yet for the prognosis of response.
To analyse whether polymorphisms of several cytokine genes are associated with the responsiveness to TNF blockade with etanercept.
123 patients with active RA were treated with etanercept and response rates were determined after three months using American College of Rheumatology (ACR)20 and disease activity score (DAS)28 response criteria. Genotyping was done for TNF (-308 TNFA), interleukin (IL)10 (-1087 IL10), transforming growth factor (TGF)beta1 (codon 25 TGFB1), and IL1 receptor antagonist (intron 2 IL1RN).
24 patients (20%) were defined as non-responders owing to their failure to fulfil any of the ACR20 or DAS28 response criteria. None of the recorded alleles was alone significantly associated with responsiveness to treatment. However, a certain combination of alleles (-308 TNF1/TNF1 and -1087 G/G) was associated with good responsiveness to etanercept (p<0.05). In addition, a combination of alleles influencing interleukin 1 receptor antagonist (IL1Ra) and TGFbeta1 production (A2 allele for IL1RN and rare C allele in codon 25 of TGFB1 gene) was associated with non-responsiveness (p<0.05).
Genetic polymorphisms, which may influence the balance of pro- and anti-inflammatory cytokines of relevance for the course of RA, are associated with clinical responsiveness to etanercept treatment.
类风湿关节炎（RA）是一种基因复杂的疾病，不同患者对不同治疗的反应差异很大。肿瘤坏死因子（TNF）阻断剂的情况就是如此，据描述有20% - 40%的患者对其无反应。目前尚无反应预后的预测标志物。
分析几种细胞因子基因的多态性是否与依那西普TNF阻断反应性相关。
123例活动期RA患者接受依那西普治疗，3个月后根据美国风湿病学会（ACR）20和疾病活动评分（DAS）28反应标准确定反应率。对TNF（-308 TNFA）、白细胞介素（IL）10（-1087 IL10）、转化生长因子（TGF）β1（密码子25 TGFB1）和IL1受体拮抗剂（内含子2 IL1RN）进行基因分型。
24例患者（20%）因未达到ACR20或DAS28反应标准而被定义为无反应者。所记录的等位基因中没有一个单独与治疗反应性显著相关。然而，特定的等位基因组合（-308 TNF1/TNF1和-1087 G/G）与依那西普的良好反应性相关（p<0.05）。此外，影响白细胞介素1受体拮抗剂（IL1Ra）和TGFβ1产生的等位基因组合（IL1RN的A2等位基因和TGFB1基因密码子25中的罕见C等位基因）与无反应性相关（p<0.05）。
可能影响与RA病程相关的促炎和抗炎细胞因子平衡的基因多态性与依那西普治疗的临床反应性相关。
