{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T23:04:47Z","timestamp":1790809487439,"version":"4.1.0"},"reference-count":126,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T00:00:00Z","timestamp":1753660800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms26157274","type":"journal-article","created":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T10:51:14Z","timestamp":1753699874000},"page":"7274","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Molecular Insight into the Role of HLA Genotypes in Immunogenicity and Secondary Refractoriness to Anti-TNF Therapy in IBD Patients"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8259-6060","authenticated-orcid":false,"given":"Mladen","family":"Maksic","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34000 Kragujevac, Serbia"},{"name":"Clinic of Gastroenterology and Hepatology, University Clinical Centre Kragujevac, Zmaj Jovina 30, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4675-4344","authenticated-orcid":false,"given":"Irfan","family":"Corovic","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34000 Kragujevac, Serbia"},{"name":"Department of Internal Medicine, General Hospital of Novi Pazar, Generala Zivkovica 1, 36300 Novi Pazar, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tijana","family":"Maksic","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34000 Kragujevac, Serbia"},{"name":"Pediatric Clinic, University Clinical Centre Kragujevac, Zmaj Jovina 30, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jelena","family":"Zivic","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34000 Kragujevac, Serbia"},{"name":"Clinic of Gastroenterology and Hepatology, University Clinical Centre Kragujevac, Zmaj Jovina 30, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9119-0692","authenticated-orcid":false,"given":"Milos","family":"Zivic","sequence":"additional","affiliation":[{"name":"Department of Dentistry, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34000 Kragujevac, Serbia"},{"name":"Department of Maxillofacial Surgery, Clinic of Otorhinolaryngology, University Clinical Centre Kragujevac, Zmaj Jovina 30, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasa","family":"Zdravkovic","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34000 Kragujevac, Serbia"},{"name":"Clinic of Gastroenterology and Hepatology, University Clinical Centre Kragujevac, Zmaj Jovina 30, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0230-4369","authenticated-orcid":false,"given":"Aleksa","family":"Begovic","sequence":"additional","affiliation":[{"name":"Digestive Endoscopy Unit, University Clinic Dr Dragisa Misovic-Dedinje, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marija","family":"Medovic","sequence":"additional","affiliation":[{"name":"Department of Dermatovenerology, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34000 Kragujevac, Serbia"},{"name":"Centre for Dermatovenerology, University Clinical Centre Kragujevac, Zmaj Jovina 30, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9153-2153","authenticated-orcid":false,"given":"Djordje","family":"Kralj","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, University Hospital Medical Center Zvezdara, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9989-5921","authenticated-orcid":false,"given":"Zeljko","family":"Todorovic","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34000 Kragujevac, Serbia"},{"name":"Clinic of Hematology, University Clinical Centre Kragujevac, Zmaj Jovina 30, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milica","family":"Cekerevac","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34000 Kragujevac, Serbia"},{"name":"Pediatric Clinic, University Clinical Centre Kragujevac, Zmaj Jovina 30, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rasa","family":"Medovic","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34000 Kragujevac, Serbia"},{"name":"Pediatric Clinic, University Clinical Centre Kragujevac, Zmaj Jovina 30, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6960-3438","authenticated-orcid":false,"given":"Milos","family":"Nikolic","sequence":"additional","affiliation":[{"name":"Department of 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