Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
The First Clinical Medical College, Anhui Medical University, Hefei, China.
Int J Immunogenet. 2024 Dec;51(6):380-387. doi: 10.1111/iji.12696. Epub 2024 Oct 10.
Carriage of HLA-DQA105 is thought to increase the formation of anti-tumour necrosis factor alpha (TNF-α) antibodies, reducing the drug efficacy in Crohn's disease (CD) patients. However, little data are currently available for small-bowel Crohn's disease (SB-CD). A specific assessment of the impact of HLA-DQA105 on the clinical response to treatment with infliximab (IFX), a TNF-α antagonists, in SB-CD patients is necessary. We conducted a single-center retrospective study that included 106 SB-CD patients treated with IFX. The serum samples were collected for antibodies to infliximab (ATI) testing and HLA-DQA105 genotyping. Double-balloon enteroscopy (DBE) was performed following the IFX treatment, with endoscopic outcomes evaluated using the partial simple endoscopic score for CD (pSES-CD), whereas the clinical response was assessed with the Crohn's disease activity index (CDAI). Multivariate logistic regression and multivariate COX regression analyses were employed to analyze the correlation of the HLA-DQA105 genotypes with other clinical variables. In this study, 30.2% of SB-CD patients carried the HLA-DQA105 allele, which significantly increased their risk of ATI generation (odds ratio [OR] = 2.337, p = .043), but it was not associated with the clinical response to IFX and drug persistence (OR = 2.356, p = .145; OR = 0.457, p = .249). The endoscopic remission rates were 40.6% (13/32) and 55.4% (41/74) in HLA-DQA105 carriers and non-carriers, respectively. HLA-DQA105 was not associated with endoscopic remission (OR = 0.684, p = .414). The HLA-DQA105 variant is identified as a significant risk factor of ATI formation in Chinese patients with SB-CD, but is not associated with the clinical response of IFX treatment and endoscopic remission of SB lesions.
携带 HLA-DQA105 被认为会增加抗肿瘤坏死因子-α(TNF-α)抗体的形成,从而降低克罗恩病(CD)患者使用 TNF-α拮抗剂英夫利昔单抗(IFX)的疗效。然而,目前关于小肠道 CD(SB-CD)的数据很少。因此,有必要对 HLA-DQA105 对 SB-CD 患者接受 IFX 治疗的临床反应的影响进行专门评估。我们进行了一项单中心回顾性研究,纳入了 106 例接受 IFX 治疗的 SB-CD 患者。采集血清样本进行抗 IFX 抗体(ATI)检测和 HLA-DQA105 基因分型。在 IFX 治疗后进行双气囊小肠镜检查(DBE),采用 CD 部分简单内镜评分(pSES-CD)评估内镜结果,采用克罗恩病活动指数(CDAI)评估临床反应。采用多变量逻辑回归和多变量 COX 回归分析来分析 HLA-DQA105 基因型与其他临床变量的相关性。在这项研究中,30.2%的 SB-CD 患者携带 HLA-DQA105 等位基因,这显著增加了他们产生 ATI 的风险(比值比 [OR] = 2.337,p =.043),但与 IFX 的临床反应和药物维持无关(OR = 2.356,p =.145;OR = 0.457,p =.249)。HLA-DQA105 携带者和非携带者的内镜缓解率分别为 40.6%(13/32)和 55.4%(41/74)。HLA-DQA105 与内镜缓解无关(OR = 0.684,p =.414)。HLA-DQA105 变异被确定为中国 SB-CD 患者 ATI 形成的重要危险因素,但与 IFX 治疗的临床反应和 SB 病变的内镜缓解无关。