Gastroenterology Unit, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofía, Universidad de Córdoba, 14004 Córdoba, Spain.
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 28029 Madrid, Spain.
Int J Mol Sci. 2023 May 12;24(10):8695. doi: 10.3390/ijms24108695.
Therapy with anti-tumor necrosis factor (TNF) has dramatically changed the natural history of Crohn's disease (CD). However, these drugs are not without adverse events, and up to 40% of patients could lose efficacy in the long term. We aimed to identify reliable markers of response to anti-TNF drugs in patients with CD. A consecutive cohort of 113 anti-TNF naive patients with CD was stratified according to clinical response as short-term remission (STR) or non-STR (NSTR) at 12 weeks of treatment. We compared the protein expression profiles of plasma samples in a subset of patients from both groups prior to anti-TNF therapy by SWATH proteomics. We identified 18 differentially expressed proteins ( ≤ 0.01, fold change ≥ 2.4) involved in the organization of the cytoskeleton and cell junction, hemostasis/platelet function, carbohydrate metabolism, and immune response as candidate biomarkers of STR. Among them, vinculin was one of the most deregulated proteins ( < 0.001), whose differential expression was confirmed by ELISA ( = 0.054). In the multivariate analysis, plasma vinculin levels along with basal CD Activity Index, corticosteroids induction, and bowel resection were factors predicting NSTR.
抗肿瘤坏死因子（TNF）治疗极大地改变了克罗恩病（CD）的自然病程。然而，这些药物并非没有不良反应，多达 40%的患者在长期内可能会失去疗效。我们旨在确定 CD 患者对抗 TNF 药物反应的可靠标志物。根据治疗 12 周时的短期缓解（STR）或非 STR（NSTR），对 113 例抗 TNF 初治 CD 患者进行连续队列分层。在抗 TNF 治疗之前，我们通过 SWATH 蛋白质组学比较了两组患者中部分患者的血浆样本的蛋白质表达谱。我们鉴定出 18 种差异表达的蛋白质（≤0.01，倍数变化≥2.4），这些蛋白质涉及细胞骨架和细胞连接、止血/血小板功能、碳水化合物代谢和免疫反应的组织，作为 STR 的候选生物标志物。其中，粘着斑蛋白是最失调的蛋白质之一（<0.001），其差异表达通过 ELISA 得到证实（=0.054）。在多变量分析中，血浆粘着斑蛋白水平以及基础 CD 活动指数、皮质类固醇诱导和肠切除术是预测 NSTR 的因素。
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