Department of Medicine I (Gastroenterology), Ulm University, Albert-Einstein-Allee 23, 89081 Ulm, Germany.
Dig Dis Sci. 2012 Apr;57(4):879-86. doi: 10.1007/s10620-011-1977-3. Epub 2011 Dec 7.
Great efforts have been made to predict disease behavior over time and the response to treatment in Crohn's disease (CD). Such understanding could personalize therapy. Early introduction of more aggressive therapies to patients at high risk and no introduction of predictable refractory treatments could become possible. We hence tested the influence of the NOD2 carrier status on treatment response.
In 185 CD patients (age 45 ± 9.8 years, female n = 108, minimum disease duration 10 years), the three most common polymorphisms (p.Arg702Trp, p.Gly908Arg, p.Leu1007fsX1008) of NOD2 were tested by polymerase chain reaction and sequencing. Detailed clinical and medical history were obtained with a standardized questionnaire and by reviewing the medical charts. Treatments introduced were chosen by physicians blinded to genotype data.
The frequency of the NOD2 variant allele was about one-third (67, 30.2%) of CD patients. NOD2 carriers were more often treated with systemic and locally active steroids and with an immunosuppressant (Azathioprine/6-MP). NOD2 mutation carrier status was more often associated with systemic steroid [8.9% vs. wild-type (WT) 1.2%, P = 0.0086] and local-steroid refractory (14.9% vs. WT 3.5%; P = 0.001). The WT patients were significantly higher refractory to immunosuppressant (12.8% vs. NOD2 carriers, 0.5%, P = 0.03). Most WT patients were treated with TNF-α antagonists and remission rates were significantly higher in this group after 1 year of treatment (84% vs. NOD2 carriers, 33%, P = 0.07).
The study presents first hints for the NOD2 carrier status to be predictive for response to therapy. A higher percentage of CD patients with NOD2 mutation carrier status was steroid refractory but could be treated well with immunosuppressants. The WT status showed a higher response to steroids and remission rates within 1 year of anti-TNF-α therapy. On the way to personalized medicine, this approach should be further investigated in larger studies.
人们在预测克罗恩病（CD）的疾病行为和对治疗的反应方面付出了巨大努力。这种理解可以使治疗个性化。对于高危患者，可以尽早引入更积极的治疗方法，并且可以避免使用可预测的难治性治疗方法。因此，我们检测了 NOD2 携带者状态对治疗反应的影响。
在 185 名 CD 患者（年龄 45 ± 9.8 岁，女性 n = 108 名，最短疾病持续时间 10 年）中，通过聚合酶链反应和测序检测 NOD2 的三种最常见的多态性（p.Arg702Trp、p.Gly908Arg、p.Leu1007fsX1008）。通过标准化问卷和审查病历获得详细的临床和病史。引入的治疗方法由对基因型数据盲法的医生选择。
NOD2 变异等位基因的频率约为三分之一（67 例，30.2%）的 CD 患者。NOD2 携带者更常接受全身性和局部活性类固醇和免疫抑制剂（硫唑嘌呤/6-MP）治疗。NOD2 突变携带者状态更常与全身性类固醇相关[8.9%比野生型（WT）1.2%，P = 0.0086]和局部类固醇难治性（14.9%比 WT 3.5%；P = 0.001）。WT 患者对免疫抑制剂明显更具难治性（12.8%比 NOD2 携带者，0.5%，P = 0.03）。大多数 WT 患者接受 TNF-α 拮抗剂治疗，并且在治疗 1 年后，该组的缓解率显著更高（84%比 NOD2 携带者，33%，P = 0.07）。
该研究首次提示 NOD2 携带者状态可预测治疗反应。具有 NOD2 突变携带者状态的 CD 患者的比例较高，对类固醇具有难治性，但可以用免疫抑制剂很好地治疗。WT 状态对类固醇的反应更高，并且在抗 TNF-α 治疗 1 年内缓解率更高。在迈向个体化医学的道路上，应该在更大的研究中进一步研究这种方法。
