{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T19:46:06Z","timestamp":1792525566209,"version":"4.5.0"},"reference-count":39,"publisher":"Korean Endocrine Society","issue":"1","license":[{"start":{"date-parts":[[2022,2,28]],"date-time":"2022-02-28T00:00:00Z","timestamp":1646006400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Science, Sports, and Culture","doi-asserted-by":"crossref","award":["20K17541"],"award-info":[{"award-number":["20K17541"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Science, Sports, and Culture","doi-asserted-by":"crossref","award":["21K08544"],"award-info":[{"award-number":["21K08544"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["e-enm.org"],"crossmark-restriction":true},"short-container-title":["Endocrinol Metab"],"published-print":{"date-parts":[[2022,2,28]]},"abstract":"<jats:p>Background: Type 1 diabetes mellitus induced by immune-checkpoint inhibitors (ICI-T1DM) is a rare critical entity. However, the etiology of ICI-T1DM remains unclear.Methods: In order to elucidate risk factors for ICI-T1DM, we evaluated the clinical course and immunological status of patients with ICI-T1DM who had been diagnosed during 2016 to 2021.Results: Seven of 871 (0.8%, six men and one woman) patients developed ICI-T1DM. We revealed that the allele frequencies of human leukocyte antigen (HLA)-DPA1*02:02 and DPB1*05:01 were significantly higher in the patients with ICI-T1DM In comparison to the controls who received ICI (11\/14 vs. 10\/26, &lt;i&gt;P&lt;\/i&gt;=0.022; 11\/14 vs. 7\/26, &lt;i&gt;P&lt;\/i&gt;=0.0027, respectively). HLA-DRB1*04:05, which has been found to be a T1DM susceptibility allele in Asians, was also observed as a high-risk allele for ICI-T1DM. The significance of the HLA-DPB1*05:01 and DRB1*04:05 alleles was confirmed by an analysis of four additional patients. The absolute\/relative neutrophil count, neutrophils-lymphocyte ratio, and neutrophil-eosinophil ratio increased, and the absolute lymphocyte count and absolute\/relative eosinophil count decreased at the onset as compared with 6 weeks before. In two patients, alterations in cytokines and chemokines were found at the onset.Conclusion: Novel high-risk HLA alleles and haplotypes were identified in ICI-T1DM, and peripheral blood factors may be utilized as biomarkers.<\/jats:p>","DOI":"10.3803\/enm.2021.1282","type":"journal-article","created":{"date-parts":[[2022,2,28]],"date-time":"2022-02-28T08:14:01Z","timestamp":1646036041000},"page":"84-95","update-policy":"https:\/\/doi.org\/10.3803\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Human Leukocyte Antigens and Biomarkers in Type 1 Diabetes Mellitus Induced by Immune-Checkpoint Inhibitors"],"prefix":"10.3803","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7718-734X","authenticated-orcid":true,"given":"Hidefumi","family":"Inaba","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yosuke","family":"Kaido","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saya","family":"Ito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomonao","family":"Hirobata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gen","family":"Inoue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takakazu","family":"Sugita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masatoshi","family":"Jinnin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Kimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shintaro","family":"Iwama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Arima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takaaki","family":"Matsuoka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2119","reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxu076"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxm057"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1507\/endocrj.ej19-0163"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.2169\/internalmedicine.9518-17"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1507\/endocrj.ej19-0234"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1111\/cen.14082"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1111\/cas.14363"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1507\/endocrj.ej20-0371"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2017.07.007"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.31557\/apjcp.2020.21.6.1697"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1111\/jdi.12024"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1111\/jdi.12119"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1186\/s40425-018-0383-1"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2008.12.034"},{"key":"ref15","first-page":"1065","volume-title":"","author":"Imanishi","year":"1992"},{"key":"ref16","volume-title":"","year":"2022"},{"key":"ref17","volume-title":"","year":"2022"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2021-002493"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1507\/endocrj.ej20-0769"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.2337\/dbi18-0002"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1007\/s12094-020-02420-9"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.00913"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1016\/j.dsx.2016.12.021"},{"key":"ref24","first-page":"1084","volume-title":"HLA 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