{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T12:12:43Z","timestamp":1777896763806,"version":"3.51.4"},"reference-count":53,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014810","name":"Fondazione di Sardegna","doi-asserted-by":"crossref","award":["RICALTRO_CTC_2020_ROSSINO"],"award-info":[{"award-number":["RICALTRO_CTC_2020_ROSSINO"]}],"id":[{"id":"10.13039\/100014810","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Celiac disease (CD) is a multifactorial autoimmune disorder strongly associated with specific HLA class II molecules, particularly HLA-DQ\u2013encoding haplotypes. Although the genetic contribution of these loci is well established, the structural features accompanying allele-specific disease susceptibility remain incompletely explored. Methods: In this study, molecular HLA typing was integrated with in silico secondary structure analysis to examine the relationship between genetic predisposition and structural organization of HLA class II molecules in a Sardinian population. A total of 100 patients with CD and 100 healthy controls were genotyped for HLA-DR and HLA-DQ alleles, and allelic and haplotypic distributions were compared between groups. Secondary structure predictions were performed using PSIPRED on selected HLA class II alleles, focusing on groove-forming domains of HLA-DRB1 and HLA-DQA1. Results: CD patients showed a marked enrichment of the DR3\u2013DQ2.5 haplotype, together with a population-specific predominance of DQ2.5 and a reduced contribution of DQ8. Secondary structure analysis of the HLA-DRB1 \u03b21 domain revealed a largely conserved organization, with only modest allele-dependent variations. In contrast, comparative analysis of HLA-DQA1 identified localized differences within the \u03b11 domain, with the DQ2.5 molecule displaying a more coherent secondary structure organization compared with the lower-risk DQ2.2 variant. Conclusions: By integrating genetic and in silico structural analyses, this study highlights that HLA-associated susceptibility to celiac disease reflects not only allele and haplotype distribution but also subtle, allele-specific features in the structural organization of peptide-binding regions. These findings provide a refined framework for interpreting HLA-DQ\u2013mediated genetic risk and support the relevance of structural coherence as a complementary dimension in the assessment of disease susceptibility.<\/jats:p>","DOI":"10.3390\/genes17020145","type":"journal-article","created":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T15:04:46Z","timestamp":1769612686000},"page":"145","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Structural Insights into HLA-DQ\u2013Associated Susceptibility to Celiac Disease Through an Integrated Genetic and In Silico Approach in a Sardinian Population"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1604-1918","authenticated-orcid":false,"given":"Faustina Barbara","family":"Cannea","sequence":"first","affiliation":[{"name":"Department of Life and Environmental Sciences (DiSVA), Biomedical Section, University of Cagliari, Cittadella Universitaria di Monserrato, 09042 Monserrato, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9191-6941","authenticated-orcid":false,"given":"Daniela","family":"Diana","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences (DiSB), University of Cagliari, Cittadella Universitaria di Monserrato, 09042 Monserrato, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3850-2949","authenticated-orcid":false,"given":"Rossano","family":"Rossino","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Public Health (DSMSP), University of Cagliari, AOU Presidio Microcitemico, Via Jenner, 09121 Cagliari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0540-3082","authenticated-orcid":false,"given":"Alessandra","family":"Padiglia","sequence":"additional","affiliation":[{"name":"Department of Life and Environmental Sciences (DiSVA), Biomedical Section, University of Cagliari, Cittadella Universitaria di Monserrato, 09042 Monserrato, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1016\/0016-5085(93)90912-V","article-title":"HLA susceptibility genes in celiac disease: Genetic mapping and role in pathogenesis","volume":"105","author":"Sollid","year":"1993","journal-title":"Gastroenterology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1136\/gutjnl-2011-301346","article-title":"The Oslo definitions for coeliac disease and related terms","volume":"62","author":"Ludvigsson","year":"2013","journal-title":"Gut"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1146\/annurev-immunol-040210-092915","article-title":"Integration of genetic and immunological insights into a model of celiac disease pathogenesis","volume":"29","author":"Abadie","year":"2011","journal-title":"Annu. 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