{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T21:56:07Z","timestamp":1791410167463,"version":"4.3.3"},"reference-count":60,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Type 1 diabetes mellitus (T1D) is an autoimmune disease with a strong genetic predisposition, largely conferred by human leukocyte antigen (HLA) class II genes. Patients with T1D frequently develop additional autoimmune diseases (AIDs). However, data on HLA class II alleles and haplotypes associated with concomitant autoimmune diseases in T1D remain limited, particularly in Central European populations. This study aimed to investigate the distribution of HLA class II allele variants and haplotypes in patients with T1D with and without concomitant autoimmune diseases affecting the thyroid, gastrointestinal tract, and skin.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This cross-sectional study included 149 T1D patients who underwent low- to intermediate-resolution HLA typing of\n                      <jats:italic>HLA-DRB1, -DQA1<\/jats:italic>\n                      and\n                      <jats:italic>-DQB1<\/jats:italic>\n                      loci at the Department of HLA Typing and Genomic Diagnostics, University Hospital Centre Osijek, Croatia, between 2009 and 2026. Clinical data on associated autoimmune diseases were retrieved from electronic medical records. Previously published HLA class-II typing data of 111 unrelated blood donors from eastern Croatia were used as the control group.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 149 T1D patients, 55 (36.9%) had a concomitant autoimmune disease, most commonly affecting the thyroid (23.5%), gastrointestinal tract (7.4%), or skin (6.0%). The\n                      <jats:italic>HLA-DRB1*03<\/jats:italic>\n                      allele variant and\n                      <jats:italic>HLA-DQA1*05-DQB1*02-DRB1*03<\/jats:italic>\n                      (DR3-DQ2) haplotype showed the strongest association of T1D (OR 5.15 and OR 5.52, respectively; p &amp;lt; 0.001), whereas\n                      <jats:italic>HLA-DRB1*04<\/jats:italic>\n                      allele variant and\n                      <jats:italic>HLA-DQA1*03-DQB1*03(DQ8)-DRB1*04<\/jats:italic>\n                      (DR4-DQ8) haplotype showed the strongest association of T1D with concomitant autoimmune disease (OR 4.86 and OR 5.91, respectively; p &amp;lt; 0.001). No significant differences in HLA allele or haplotype frequencies were observed between patients with T1D alone and those with T1D and concomitant autoimmune disease.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings confirm the established role of the HLA-DR3-DQ2 and HLA-DR4-DQ8 haplotypes in genetic susceptibility to T1D in a Central European population. Because a direct comparison between the T1D-alone and T1D+AID groups did not reveal significant differences, DR4-DQ8 should be interpreted as being associated with an increased risk of both phenotypes relative to healthy controls, rather than as specifically distinguishing patients with autoimmune comorbidities from those without. Given the small number of patients within individual comorbidity subgroups, disease-specific HLA associations could not be evaluated separately. Independent replication in larger, multicenter cohorts with high-resolution HLA typing is needed before these findings can be applied in clinical practice.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1928474","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T04:46:04Z","timestamp":1785905164000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["HLA class II alleles and haplotypes associated with susceptibility to type 1 diabetes and to type 1 diabetes with concomitant autoimmune diseases: a cross-sectional study from Eastern Croatia"],"prefix":"10.3389","volume":"17","author":[{"given":"Ivan","family":"Leki\u0107","sequence":"first","affiliation":[{"name":"Department of Internal Medicine and History of Medicine, Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek","place":["Osijek, Croatia"]},{"name":"Department of Internal Medicine, 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