Martinez Alfonso, Salido Marina, Bonilla Gema, Pascual-Salcedo Dora, Fernandez-Arquero Miguel, de Miguel Sonia, Balsa Alejandro, de la Concha Emilio G, Fernandez-Gutierrez Benjamin
Hospital Clinico San Carlos, Madrid, Spain.
Arthritis Rheum. 2004 Apr;50(4):1077-82. doi: 10.1002/art.20154.
To determine whether major histocompatibility complex (MHC) polymorphisms are associated with a good or poor response to infliximab therapy in patients with rheumatoid arthritis (RA).
Seventy-eight infliximab-treated patients with RA were genotyped for HLA-DRB1, HLA-DQA1, HLA-DQB1, MHC class I chain-related gene A (MICA) transmembrane polymorphism alleles, and tumor necrosis factor a (TNFa), TNFb, TNFc, TNFd, TNFe, D6S273, HLA-B-associated transcript 2 (BAT2), and D6S2223 microsatellites. Chi-square tests were performed to compare allele proportions between responder and nonresponder patients. A control sample of 342 healthy individuals was also included to detect linkage disequilibrium between pairs of markers.
Among responders, the frequency of the TNFa11;b4 minihaplotype was increased (41% versus 16% in nonresponders; P = 0.01) and that of the D6S273_3 allele was decreased (32% versus 56% in nonresponders; P = 0.04). The D6S273_4/BAT2_2 pair was much more frequently observed among responders (46% versus 11% in nonresponders; P = 0.001). When compared with controls, this pair of alleles was found to be associated only with the group of responder patients (46% in responders versus 17% in controls; P = 0.00002). Most of the time, these markers are present in a DRB1*0404/D6S273_4/BAT2_2/TNFa11;b4 context. No statistically significant differences were observed for MICA and D6S2223 polymorphisms and for shared epitope status.
The data suggest that genetic determinants of response to infliximab therapy exist in the HLA complex.
确定主要组织相容性复合体（MHC）多态性是否与类风湿关节炎（RA）患者对英夫利昔单抗治疗的反应良好或不佳相关。
对78例接受英夫利昔单抗治疗的RA患者进行HLA-DRB1、HLA-DQA1、HLA-DQB1、MHC I类链相关基因A（MICA）跨膜多态性等位基因，以及肿瘤坏死因子α（TNFα）、TNFβ、TNFγ、TNFδ、TNFe、D6S273、HLA-B相关转录本2（BAT2）和D6S2223微卫星的基因分型。进行卡方检验以比较反应者和无反应者患者之间的等位基因比例。还纳入了342名健康个体的对照样本，以检测标记对之间的连锁不平衡。
在反应者中，TNFα11;β4单倍型的频率增加（无反应者中为41%，而无反应者中为16%；P = 0.01），D6S273_3等位基因的频率降低（无反应者中为32%，而无反应者中为56%；P = 0.04）。D6S273_4/BAT2_2对在反应者中观察到的频率更高（无反应者中为46%，而无反应者中为11%；P = 0.001）。与对照组相比，发现这对等位基因仅与反应者患者组相关（反应者中为46%，而对照组中为17%；P = 0.00002）。大多数情况下，这些标记存在于DRB1*0404/D6S273_4/BAT2_2/TNFα11;β4背景中。对于MICA和D6S2223多态性以及共享表位状态，未观察到统计学上的显著差异。
数据表明，HLA复合体中存在对英夫利昔单抗治疗反应的遗传决定因素。
