{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T23:30:04Z","timestamp":1791847804539,"version":"4.3.4"},"reference-count":67,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"31","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:p>Bullous pemphigoid (BP) is a common autoimmune skin disorder caused by autoantibodies targeting BP180. Recent evidence shows that dipeptidyl peptidase-4 inhibitors (DPP4i), used in diabetes management, can induce BP (DPP4i-BP). DPP4i-BP differs from typical BP in its genetic, clinical, and immunological features, but methods to specifically detect DPP4i-BP autoantibodies have been unavailable. This study used enzyme-linked immunosorbent assay with \u201cdomain-swapped BP180\u201d proteins to identify autoantibodies in DPP4i-BP, which targeted BP180 regions from the seventh noncollagenous domain to the fourth collagenous domain (NC7-Col4). These epitopes were associated with DPP4i-BP\u2013specific human leukocyte antigen class II peptide epitopes. Notably, the duration of DPP4i intake before BP onset was significantly shorter in patients with anti\u2013NC7-Col4 autoantibodies than those without them. Measuring the autoantibodies enabled the early diagnosis of DPP4i-BP before epitope spreading. Furthermore, anti\u2013NC7-Col4 autoantibodies were detected in some patients with diabetes taking DPP4i without BP, suggesting that these assays may offer potential tools for early identification of at-risk individuals.<\/jats:p>","DOI":"10.1126\/sciadv.adv9423","type":"journal-article","created":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T17:58:22Z","timestamp":1754071102000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":6,"title":["Identification of distinct epitopes in dipeptidyl peptidase-4 inhibitor\u2013associated bullous pemphigoid"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5468-6851","authenticated-orcid":true,"given":"Shoko","family":"Mai","sequence":"first","affiliation":[{"name":"Department of Dermatology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6356-7192","authenticated-orcid":true,"given":"Yosuke","family":"Mai","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7931-949X","authenticated-orcid":true,"given":"Inkin","family":"Ujiie","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8221-9644","authenticated-orcid":true,"given":"Kentaro","family":"Izumi","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3865-6366","authenticated-orcid":true,"given":"Ken","family":"Natsuga","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0486-9112","authenticated-orcid":true,"given":"Wataru","family":"Nishie","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3489-5418","authenticated-orcid":true,"given":"Hideyuki","family":"Ujiie","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)61140-4"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2017.03.010"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2020.02.013"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2021.11.003"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2018.00220"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116368"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12319337"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0625.1998.tb00329.x"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114036"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12616580"},{"key":"e_1_3_2_12_2","first-page":"352","article-title":"Cloning of the human type XVII collagen gene (COL17A1), and detection of novel mutations in generalized atrophic benign epidermolysis bullosa","volume":"60","author":"Gatalica B.","year":"1997","unstructured":"B. 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