{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T19:14:11Z","timestamp":1781118851255,"version":"3.54.1"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,8,26]],"date-time":"2024-08-26T00:00:00Z","timestamp":1724630400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,8,26]],"date-time":"2024-08-26T00:00:00Z","timestamp":1724630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004047","name":"Karolinska Institute","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004047","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pediatr Rheumatol"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Juvenile Idiopathic Arthritis (JIA) is a complex autoimmune disease and the most common chronic rheumatological disease affecting children under the age of 16. The etiology of JIA remains poorly understood, but evidence suggests a significant genetic predisposition.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We analyzed a Swedish cohort of 329 JIA patients and 728 healthy adult controls using the Illumina OmniExpress array for genotyping. HLA alleles were imputed from GWAS data using the SNP2HLA algorithm.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Case\u2013control analysis yielded 12 SNPs with genome-wide significant association to JIA, all located on chromosome 6 within the MHC class II gene region. Notably, the top SNP (rs28421666) was located adjacent to <jats:italic>HLA-DQA1<\/jats:italic> and <jats:italic>HLA-DRB1<\/jats:italic>. <jats:italic>HLA-DRB1*<\/jats:italic>08:01, <jats:italic>HLA-DQA1*<\/jats:italic>04:01, and <jats:italic>HLA-DQB1*<\/jats:italic>04:02 were the haplotypes most strongly associated with an increased risk of JIA in the overall cohort. When analyzing disease specific subtypes, these alleles were associated with oligoarthritis and RF-negative polyarthritis. Within the complex linkage disequilibrium of the <jats:italic>HLA-DRB1-DQA1-DQB1<\/jats:italic> haplotype, our analysis suggests that <jats:italic>HLA-DRB1*<\/jats:italic>08 might be the primary allele linked to JIA susceptibility. The <jats:italic>HLA-DRB1*<\/jats:italic>11 allele group was also independently associated with JIA and specifically enriched in the oligoarthritis patient group. Additionally, our study revealed a significant correlation between antinuclear antibody (ANA) positivity and specific HLA alleles. The ANA-positive JIA group showed stronger associations with the <jats:italic>HLA-DRB1-DQA1-DQB1<\/jats:italic> haplotype, <jats:italic>HLA-DRB1*<\/jats:italic>11, and <jats:italic>HLA-DPB1*<\/jats:italic>02, suggesting a potential connection between genetic factors and ANA production in JIA. Furthermore, logistic regression analysis reaffirmed the effects of HLA alleles, female sex, and lower age at onset on ANA positivity.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>This study identified distinct genetic associations between HLA alleles and JIA subtypes, particularly in ANA-positive patients. These findings contribute to a better understanding of the genetic basis of JIA and provide insights into the genetic control of autoantibody production in ANA-positive JIA patients. This may inform future classification and personalized treatment approaches for JIA, ultimately improving patient outcomes and management of this disease.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12969-024-01017-8","type":"journal-article","created":{"date-parts":[[2024,8,26]],"date-time":"2024-08-26T12:02:17Z","timestamp":1724673737000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Genetic association of antinuclear antibodies with HLA in JIA patients: a Swedish cohort study"],"prefix":"10.1186","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-0748-0794","authenticated-orcid":false,"given":"Raya","family":"Saleh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Sundberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mia","family":"Olsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarina","family":"Tengvall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Alfredsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid","family":"Kockum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonid","family":"Padyukov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena Erlandsson","family":"Harris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,8,26]]},"reference":[{"issue":"2","key":"1017_CR1","first-page":"390","volume":"31","author":"RE Petty","year":"2004","unstructured":"Petty RE, et al. 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