{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T00:15:24Z","timestamp":1758672924762,"version":"3.44.0"},"reference-count":23,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T00:00:00Z","timestamp":1741564800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Japan Society for the Promotion of Science KAKENHI Grant-in-Aid for Young Scientists","award":["23K14991"],"award-info":[{"award-number":["23K14991"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Very-early-onset ulcerative colitis (VEO-UC) is a severe form of inflammatory bowel disease that manifests before the age of 6 years. Compared to typical pediatric UC, it is characterized by distinct genetic and immunological factors. This study aimed to investigate the roles of specific human leukocyte antigen (HLA) alleles and maternal microchimerism (MMc) in the pathogenesis of VEO-UC in a Japanese population.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>This study included 27 VEO-UC patients, including 4 patients treated with colorectal resection. HLA typing was performed by polymerase chain reaction\u2013sequence-specific oligonucleotide probing (PCR-SSOP) and compared with the Japanese general population. Immunohistochemistry and fluorescence in situ hybridization were used to evaluate MMc in intestinal tissues. Statistical comparisons of HLA were performed against data from the general Japanese population, with Bonferroni corrections applied to handle multiple comparisons.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>HLA-B52 and HLA-DR15 were more prevalent in cases of VEO-UC than in the general Japanese population, although the statistical significance decreased after the Bonferroni correction. MMc was found in the intestinal tissues of three VEO-UC cases, whereas it was absent in the control UC cases. Maternal HLA concordance with specific alleles associated with VEO-UC was noted in several cases, suggesting maternal immune involvement in the pathogenesis of the disease.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>VEO-UC seems to share genetic traits with adult UC, such as an association with HLA-B52 and HLA-DR15, and is also affected by maternal immune contributions, as shown by the presence of MMc in the affected tissues. These findings highlight the complex interaction between genetic and immunological factors in the pathogenesis of VEO-UC and underscore the need for further research to develop targeted therapeutic strategies that address these mechanisms.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ibd\/izaf048","type":"journal-article","created":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T13:24:41Z","timestamp":1741613081000},"page":"2451-2457","source":"Crossref","is-referenced-by-count":0,"title":["The Role of Human Leukocyte Antigen Alleles and Maternal Microchimerism in Very-Early-Onset Ulcerative Colitis in Japanese Children"],"prefix":"10.1093","volume":"31","author":[{"given":"Masanori","family":"Toda","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Juntendo University Graduate School of Medicine , Tokyo ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6317-4305","authenticated-orcid":false,"given":"Keisuke","family":"Jimbo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Juntendo University Faculty of Medicine , Tokyo ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9969-3454","authenticated-orcid":false,"given":"Mitsuyoshi","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Juntendo University Faculty of Medicine , Tokyo ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masumi","family":"Nagata","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Juntendo University Faculty of Medicine , Tokyo ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7276-8201","authenticated-orcid":false,"given":"Nobuyasu","family":"Arai","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Juntendo University Faculty of Medicine , Tokyo ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaori","family":"Tokushima","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Juntendo University Graduate School of Medicine , Tokyo ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eri","family":"Miyata","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Juntendo University Faculty of Medicine , Tokyo ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuka","family":"Nagano","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate School of Medicine , Mie ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuki","family":"Koike","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate School of Medicine , Mie ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keiichi","family":"Uchida","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Mie Prefectural General Medical Center , Mie ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4708-8049","authenticated-orcid":false,"given":"Takahiro","family":"Kudo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Juntendo University Graduate School of Medicine , Tokyo ,","place":["Japan"]},{"name":"Department of Pediatrics, Juntendo University Faculty of Medicine , Tokyo ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuji","family":"Toiyama","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate School of Medicine , Mie ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshiaki","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Juntendo University Graduate School of Medicine , Tokyo ,","place":["Japan"]},{"name":"Department of Pediatrics, Juntendo University Faculty of Medicine , Tokyo ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,3,10]]},"reference":[{"issue":"4-5","key":"2025092307421921800_CIT0001","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1016\/j.autrev.2014.01.028","article-title":"Diagnosis and classification of ulcerative colitis","volume":"13","author":"Conrad","year":"2014","journal-title":"Autoimmun Rev."},{"issue":"27","key":"2025092307421921800_CIT0002","doi-asserted-by":"publisher","first-page":"6296","DOI":"10.3748\/wjg.v22.i27.6296","article-title":"Environmental risk factors for inflammatory bowel diseases: evidence based literature review","volume":"22","author":"Abegunde","year":"2016","journal-title":"World J Gastroenterol."},{"issue":"6","key":"2025092307421921800_CIT0003","doi-asserted-by":"publisher","first-page":"1704","DOI":"10.1053\/j.gastro.2011.02.046","article-title":"Recent insights into the genetics of inflammatory bowel disease","volume":"140","author":"Cho","year":"2011","journal-title":"Gastroenterology."},{"issue":"9","key":"2025092307421921800_CIT0004","doi-asserted-by":"publisher","first-page":"e0274117","DOI":"10.1371\/journal.pone.0274117","article-title":"Current and projected incidence trends of pediatric-onset inflammatory bowel disease in Germany based on the Saxon Pediatric IBD Registry 2000-2014\u2014a 15-year evaluation of trends","volume":"17","author":"Kern","year":"2022","journal-title":"PLoS One."},{"issue":"2","key":"2025092307421921800_CIT0005","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1097\/MPG.0000000000002035","article-title":"Management of paediatric ulcerative colitis, part 1: ambulatory care\u2014an evidence-based guideline from European Crohn\u2019s and Colitis Organization and European Society of Paediatric Gastroenterology, Hepatology and Nutrition","volume":"67","author":"Turner","year":"2018","journal-title":"J Pediatr Gastroenterol Nutr."},{"issue":"2","key":"2025092307421921800_CIT0006","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1053\/j.gastro.2012.06.025","article-title":"The age of gene discovery in very early onset inflammatory bowel disease","volume":"143","author":"Muise","year":"2012","journal-title":"Gastroenterology."},{"issue":"6","key":"2025092307421921800_CIT0007","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1038\/sj.gene.6364114","article-title":"Mapping of a disease susceptibility locus in chromosome 6p in Japanese patients with ulcerative colitis","volume":"5","author":"Nomura","year":"2004","journal-title":"Genes Immun."},{"issue":"11","key":"2025092307421921800_CIT0008","doi-asserted-by":"publisher","first-page":"2227","DOI":"10.1093\/ibd\/izad273","article-title":"HLA-DQA1*05 not associated with ustekinumab loss of response and antidrug antibodies in ulcerative colitis and Crohn\u2019s disease patients","volume":"30","author":"Colombel","year":"2024","journal-title":"Inflamm Bowel Dis."},{"issue":"1","key":"2025092307421921800_CIT0009","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1053\/j.gastro.2019.09.041","article-title":"HLA-DQA1*05 carriage associated with development of anti-drug antibodies to infliximab and adalimumab in patients with Crohn\u2019s disease","volume":"158","author":"Sazonovs","year":"2020","journal-title":"Gastroenterology."},{"issue":"9","key":"2025092307421921800_CIT0010","doi-asserted-by":"publisher","first-page":"2768","DOI":"10.1002\/art.21256","article-title":"Maternal HLA class II compatibility in men with systemic lupus erythematosus","volume":"52","author":"Anne","year":"2005","journal-title":"Arthritis Rheum."},{"issue":"9248","key":"2025092307421921800_CIT0011","doi-asserted-by":"publisher","first-page":"2156","DOI":"10.1016\/S0140-6736(00)03500-5","article-title":"Chimerism in children with juvenile dermatomyositis","volume":"356","author":"Reed","year":"2000","journal-title":"Lancet."},{"issue":"9","key":"2025092307421921800_CIT0012","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1016\/j.humimm.2018.07.001","article-title":"Ethnic variation in the incidence of biliary atresia correlates with the frequency of the most prevalent haplotype in its population","volume":"79","author":"Muraji","year":"2018","journal-title":"Hum Immunol."},{"issue":"1","key":"2025092307421921800_CIT0013","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1007\/s10875-016-0339-5","article-title":"Targeted sequencing and immunological analysis reveal the involvement of primary immunodeficiency genes in pediatric IBD: a Japanese Multicenter Study","volume":"37","author":"Suzuki","year":"2017","journal-title":"J Clin Immunol."},{"issue":"2","key":"2025092307421921800_CIT0014","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1053\/j.gastro.2007.05.029","article-title":"Development, validation, and evaluation of a pediatric ulcerative colitis activity index: a prospective multicenter study","volume":"133","author":"Turner","year":"2007","journal-title":"Gastroenterology."},{"issue":"6","key":"2025092307421921800_CIT0015","doi-asserted-by":"publisher","first-page":"1314","DOI":"10.1002\/ibd.21493","article-title":"Pediatric modification of the Montreal classification for inflammatory bowel disease: the Paris classification","volume":"17","author":"Levine","year":"2011","journal-title":"Inflamm Bowel Dis."},{"issue":"4","key":"2025092307421921800_CIT0016","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1111\/tan.12536","article-title":"Determination of HLA-A, -C, -B, -DRB1 allele and haplotype frequency in Japanese population based on family study","volume":"85","author":"Ikeda","year":"2015","journal-title":"Tissue Antigens."},{"author":"Haplotype Estimation Tool","key":"2025092307421921800_CIT0017"},{"issue":"1","key":"2025092307421921800_CIT0018","doi-asserted-by":"publisher","first-page":"27","DOI":"10.33160\/yam.2018.03.004","article-title":"Association of clinical features with human leukocyte antigen in Japanese patients with ulcerative colitis","volume":"61","author":"Iwamoto","year":"2018","journal-title":"Yonago Acta Med."},{"issue":"1","key":"2025092307421921800_CIT0019","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1097\/PAP.0000000000000327","article-title":"A pattern-based pathology approach to very early-onset inflammatory bowel disease: thinking beyond Crohn disease and ulcerative colitis","volume":"29","author":"Wilkins","year":"2022","journal-title":"Adv Anat Pathol."},{"issue":"2","key":"2025092307421921800_CIT0020","doi-asserted-by":"publisher","first-page":"50","DOI":"10.4161\/chim.2.2.16556","article-title":"Maternal microchimerism in pediatric inflammatory bowel disease","volume":"2","author":"Suskind","year":"2011","journal-title":"Chimerism"},{"issue":"5","key":"2025092307421921800_CIT0021","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1093\/ecco-jcc\/jjy212","article-title":"Distinct histopathological features at diagnosis of very early onset inflammatory bowel disease","volume":"13","author":"Conrad","year":"2019","journal-title":"J Crohns Colitis."},{"issue":"3","key":"2025092307421921800_CIT0022","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1203\/PDR.0b013e3181eb2eb4","article-title":"Maternal microchimerism in juvenile tonsils and adenoids","volume":"68","author":"Jonsson","year":"2010","journal-title":"Pediatr Res."},{"issue":"12","key":"2025092307421921800_CIT0023","doi-asserted-by":"publisher","first-page":"2131","DOI":"10.1111\/dme.14221","article-title":"Low prevalence of maternal microchimerism in peripheral blood of Japanese children with type 1 diabetes","volume":"37","author":"Ushijima","year":"2020","journal-title":"Diabet Med."}],"container-title":["Inflammatory Bowel Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ibdjournal\/advance-article-pdf\/doi\/10.1093\/ibd\/izaf048\/62369144\/izaf048.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ibdjournal\/article-pdf\/31\/9\/2451\/62369144\/izaf048.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ibdjournal\/article-pdf\/31\/9\/2451\/62369144\/izaf048.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T11:45:17Z","timestamp":1758627917000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ibdjournal\/article\/31\/9\/2451\/8068873"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,10]]},"references-count":23,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,3,10]]},"published-print":{"date-parts":[[2025,9,1]]}},"URL":"https:\/\/doi.org\/10.1093\/ibd\/izaf048","relation":{},"ISSN":["1078-0998","1536-4844"],"issn-type":[{"type":"print","value":"1078-0998"},{"type":"electronic","value":"1536-4844"}],"subject":[],"published-other":{"date-parts":[[2025,9]]},"published":{"date-parts":[[2025,3,10]]}}}