Schirru E, Rossino R, Jores RD, Corpino M, Muntoni S, Cucca F, Congia M. Clinical settings in which human leukocyte antigen typing is still useful in the diagnosis of celiac disease. World J Gastroenterol 2025; 31(14): 104397 [PMID: 40248378 DOI: 10.3748/wjg.v31.i14.104397]
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Mauro Congia, MD, Doctor, Department of Pediatrics, Clinic of Pediatric and Rare Diseases, Microcitemico Pediatric Hospital, A.Cao, ASL8, Via Jenner Cagliari, Cagliari 09121, Sardegna, Italy. maurocongia1957@gmail.com
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Schirru E, Rossino R, Jores RD, Corpino M, Muntoni S, Cucca F, Congia M. Clinical settings in which human leukocyte antigen typing is still useful in the diagnosis of celiac disease. World J Gastroenterol 2025; 31(14): 104397 [PMID: 40248378 DOI: 10.3748/wjg.v31.i14.104397]
World J Gastroenterol. Apr 14, 2025; 31(14): 104397 Published online Apr 14, 2025. doi: 10.3748/wjg.v31.i14.104397
Clinical settings in which human leukocyte antigen typing is still useful in the diagnosis of celiac disease
Enrico Schirru, Rossano Rossino, Rita D Jores, Mara Corpino, Sandro Muntoni, Francesco Cucca, Mauro Congia
Enrico Schirru, University Service Center for Animal Facility (CeSASt), University of Cagliari, Monserrato 09042, Sardinia, Italy
Rossano Rossino, Department of Medical Science and Public Health, University of Cagliari, Monserrato 09042, Sardegna, Italy
Rossano Rossino, Mara Corpino, Mauro Congia, Department of Pediatrics, Clinic of Pediatric and Rare Diseases, Microcitemico Pediatric Hospital, A.Cao, ASL8, Cagliari 09121, Sardegna, Italy
Rita D Jores, Department Outpatient Clinic, ASL8 Outpatient Clinic, Quartu Sant’Elena 09045, Sardegna, Italy
Sandro Muntoni, Department of Biomedical Science, University of Cagliari, Monserrato 09042, Sardegna, Italy
Francesco Cucca, Department of Biomedical Science, University of Sassari, Sassari 07100, Sardegna, Italy
Author contributions: Schirru E, Congia M, and Jores RD contributed to the conception and design of the work; Corpino M and Muntoni S worked on the acquisition, analysis, and interpretation of the data; Cucca F and Congia M collaborated in drafting the work and in its critical revision; Schirru E, Rossino R, Jores RD, Corpino M, Muntoni S, Cucca F, and Congia M read and approved the final version of the manuscript.
Supported by Fondazione di Sardegna, No. 2020.2284.
Conflict-of-interest statement: The authors declare that they have no conflicts of interest.
Corresponding author: Mauro Congia, MD, Doctor, Department of Pediatrics, Clinic of Pediatric and Rare Diseases, Microcitemico Pediatric Hospital, A.Cao, ASL8, Via Jenner Cagliari, Cagliari 09121, Sardegna, Italy. maurocongia1957@gmail.com
Received: December 19, 2024 Revised: February 1, 2025 Accepted: March 21, 2025 Published online: April 14, 2025 Processing time: 113 Days and 9.4 Hours
Abstract
Celiac disease (CD) is a systemic autoimmune disorder triggered by gluten ingestion ingenetically predisposed individuals. It is characterized by intestinal histological damage and the production of specific autoantibodies. The latest European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) 2020 guidelines have excluded human leukocyte antigen (HLA) genotyping from the no-biopsy diagnostic approach due to its weak positive predictive value, limited availability, and high cost in some countries. However, HLA genetic testing remains valuable in certain clinical contexts. This study provided practical indications for when to request and how to interpret HLA genotyping, emphasizing its continued relevance for CD diagnosis in specific cases. We also proposed a strategy for monitoring the risk of developing type 1 diabetes (T1D) in patients with CD, based on the risk stratification carried by different HLA genotypes. A retrospective analysis of 746 patients with CD and 627 controls was conducted at our hospital starting in 2012, when HLA genotyping became mandatory for the diagnosis of CD. We identified key clinical scenarios where HLA testing remains useful. Several high risk HLA-DQ genotypes strongly associated with CD were highlighted, including HLA-DQ2.5/HLA-DQ2.2 and HLA-DQ2.5/HLA-DQ2.5. Notably, while the HLA-DQ2.5/HLA-DQ2.2 genotype is linked to CD, it appears to confer protection against T1D. To support clinical practice, we presented a table clarifying commonly used HLA terminology, and another summarized the main clinical situations in which HLA genotyping should still be considered. These findings underscore the dual role of HLA testing: Not only can it help rule out CD in selected cases, but it also identifies patients with CD at risk for T1D, guiding personalized monitoring strategies.
Core Tip: This guide explained how to interpret human leukocyte antigens (HLA) genetics associated with celiac disease (CD) and the different clinical situations where HLA genotyping can be useful in the diagnosis of CD. It also provided a strategy based on HLA genotyping for monitoring patients with CD at risk for the future development of type 1 diabetes (T1D). Only a subset of HLA genotypes linked to CD is associated with the development of T1D. Interestingly, some HLA genotypes that carry a high risk for CD may offer protection against T1D. Therefore, HLA genotyping in patients with CD could help in identifying those at high risk for T1D, enabling proactive interventions and therapies to preserve beta cell function.
