Maksic Mladen, Corovic Irfan, Maksic Tijana, Zivic Jelena, Zivic Milos, Zdravkovic Natasa, Begovic Aleksa, Medovic Marija, Kralj Djordje, Todorovic Zeljko, Cekerevac Milica, Medovic Rasa, Nikolic Milos
Department of Internal Medicine, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34000 Kragujevac, Serbia.
Clinic of Gastroenterology and Hepatology, University Clinical Centre Kragujevac, Zmaj Jovina 30, 34000 Kragujevac, Serbia.
Int J Mol Sci. 2025 Jul 28;26(15):7274. doi: 10.3390/ijms26157274.
The emergence of anti-TNF agents has revolutionized the management of inflammatory bowel disease, yet a significant proportion of patients experience primary non-response or secondary loss of response due to immunogenicity. As the field of precision medicine advances, genetic predictors such as human leukocyte antigen (HLA) variants are gaining increasing attention. This review provides a comprehensive synthesis of current evidence on the role of HLA genotypes in inflammatory bowel disease susceptibility and disease behavior, with a focus on their mechanistic and clinical relevance in anti-TNF therapy. Special emphasis is placed on HLA-DQA1*05, a validated predictor of anti-drug antibody formation and reduced therapeutic durability. We explore the immunological basis of HLA-mediated immunogenicity, summarize pharmacogenetic and biomarker findings, and discuss how HLA typing may be integrated into treatment algorithms to improve patient stratification and long-term outcomes. As immunogenetics continues to inform clinical decision-making, understanding the interplay between HLA polymorphisms and therapeutic response offers new opportunities for biomarker-guided, personalized care in inflammatory bowel disease.
抗TNF药物的出现彻底改变了炎症性肠病的治疗方式，但由于免疫原性，仍有相当一部分患者出现原发性无反应或继发性反应丧失。随着精准医学领域的发展，诸如人类白细胞抗原（HLA）变体等基因预测指标越来越受到关注。本综述全面综合了目前关于HLA基因型在炎症性肠病易感性和疾病行为中的作用的证据，重点关注其在抗TNF治疗中的机制和临床相关性。特别强调了HLA-DQA1*05，它是抗药物抗体形成和治疗持久性降低的有效预测指标。我们探讨了HLA介导的免疫原性的免疫学基础，总结了药物遗传学和生物标志物研究结果，并讨论了如何将HLA分型纳入治疗算法以改善患者分层和长期预后。随着免疫遗传学不断为临床决策提供依据，了解HLA多态性与治疗反应之间的相互作用为炎症性肠病中生物标志物指导的个性化治疗提供了新的机会。
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