{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T04:13:15Z","timestamp":1793160795727,"version":"4.5.0"},"reference-count":25,"publisher":"BMJ","issue":"9","license":[{"start":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T00:00:00Z","timestamp":1758585600000},"content-version":"unspecified","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Else Kr\u00f6ner-Fresenius Stiftung","award":["2023_EKAE.197"],"award-info":[{"award-number":["2023_EKAE.197"]}],"id":[{"id":"https:\/\/ror.org\/03zcxha54","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Germany's Excellence Strategy","award":["EXC-2049, project number: 390688087"],"award-info":[{"award-number":["EXC-2049, project number: 390688087"]}]},{"name":"Berlin Institute of Health (BIH) Charit\u00e9 Clinician Scientist Program","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"DOI":"10.13039\/501100003042","name":"Else Kr\u00f6ner-Fresenius-Stiftung","doi-asserted-by":"publisher","award":["2020_EKEA.80"],"award-info":[{"award-number":["2020_EKEA.80"]}],"id":[{"id":"10.13039\/501100003042","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Clinical Research Group KFO 5023 BECAUSE-Y","award":["EN343\/16-1"],"award-info":[{"award-number":["EN343\/16-1"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2025,9,1]]},"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Immune-related myotoxicity (irM), including irMyocarditis and irMyositis, is a severe complication of immune checkpoint inhibitors (ICIs). Markers to identify patients at risk are missing. In this retrospective multicenter cohort study, we aimed to determine whether specific human leukocyte antigen (HLA) variants are associated with irM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Twenty patients with irMyocarditis and\/or irMyositis (median age (IQR), 67 (60\u201373) years; 7\/20 female) and 60 cancer controls (CC) without immune-related adverse events (median age (IQR), 68 (62\u201374) years; 26\/60 female) presenting to Charit\u00e9 - Universit\u00e4tsmedizin Berlin, Germany, or Kantonsspital St. Gallen, Switzerland, between September 2017 and June 2024, were included. As a second control cohort, we used HLA data from a historic dataset of 5.1\u00d710\u2076 German healthy donors (G-HD). Allele frequencies (AF) of two-field HLA types were compared between patients with irM, CC, and G-HD using logistic regression and two-sided z-tests of odds ratios (OR).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Comparison of single HLA AF between patients with irM and G-HD revealed moderate associations for irM with B*07:02 (OR 2.29; 95% CI 1.12 to 4.69; p=0.023), B*40:01 (OR 2.75; 95% CI 1.08 to 7.02; p=0.035), C*03:04 (OR 2.46; 95% CI 1.09 to 5.56; p=0.031), DPB1*04:02 (OR 2.37; 95% CI 1.16 to 4.85; p=0.018), and DQB1*06:02 (OR 2.28; 95% CI 1.12 to 4.67; p=0.024). No statistically significant differences were observed between patients with irM and CC. By contrast, multi-allelic HLA analysis identified a strong association between HLA-A*01:01-B*08:01-C*07:01, a component of the 8.1 ancestral haplotype (8.1 AH), and\n                      <jats:italic>early-onset<\/jats:italic>\n                      irM (onset \u22643 months after ICI initiation, n=11), compared with G-HD (22.7% vs 7.6%; OR 3.59; 95% CI 1.33 to 9.74; p=0.012) and CC (22.7% vs 7.5%; OR 3.62; 95% CI 1.09 to 12.12; p=0.036). Intriguingly, early-onset irM was linked to higher troponin T levels compared with late-onset irM (p=0.005, Cohen\u2019s r=0.63).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our results provide first evidence that early-onset irM with myocardial injury is linked to HLA-A*01:01-B*08:01-C*07:01, a component of the 8.1 AH, which is associated with various autoimmune diseases including idiopathic myopathies. If validated in larger cohorts, pretreatment screening for HLA-A*01:01-B*08:01-C*07:01 may help identify patients at risk of early-onset and severe irM.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2025-011590","type":"journal-article","created":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T04:55:38Z","timestamp":1758603338000},"page":"e011590","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":13,"title":["HLA-A*01:01-B*08:01-C*07:01 is linked to early-onset immune checkpoint inhibitor-induced myositis and myocarditis"],"prefix":"10.1136","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6388-9375","authenticated-orcid":false,"given":"Leonie","family":"M\u00fcller-Jensen","sequence":"first","affiliation":[{"name":"Department of Neurology with Experimental Neurology, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Berlin, Germany"},{"name":"BIH Charit\u00e9 Clinician Scientist Program, Berlin Institute of Health at Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, BIH Biomedical Innovation Academy, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9683-8390","authenticated-orcid":false,"given":"Lukas","family":"Flatz","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Eberhard Karls University of Tuebingen, Tuebingen, Germany"},{"name":"Department of Dermatology, Venereology and Allergology, Kantonsspital St. Gallen, St. Gallen, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5185-7520","authenticated-orcid":false,"given":"Omar","family":"Hasan Ali","sequence":"additional","affiliation":[{"name":"Institute of Immunobiology, Medical Research Center, Kantonsspital St. Gallen, St. Gallen, Switzerland"},{"name":"Department of Dermatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2403-4275","authenticated-orcid":false,"given":"Raphael","family":"Mohr","sequence":"additional","affiliation":[{"name":"Department of Hepatology & Gastroenterology, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2081-3098","authenticated-orcid":false,"given":"Nils","family":"Lachmann","sequence":"additional","affiliation":[{"name":"Institute of Transfusion Medicine, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas","family":"M\u00f6dl","sequence":"additional","affiliation":[{"name":"Institute of Biometry and Clinical Epidemiology, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6520-3720","authenticated-orcid":false,"given":"Matthias","family":"Endres","sequence":"additional","affiliation":[{"name":"Department of Neurology with Experimental Neurology, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Berlin, Germany"},{"name":"NeuroCure Cluster of Excellence, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Berlin, 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