{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T18:30:32Z","timestamp":1784140232148,"version":"3.55.0"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T00:00:00Z","timestamp":1751241600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012659","name":"Foundation for Innovative Research Groups of the National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81772261"],"award-info":[{"award-number":["81772261"]}],"id":[{"id":"10.13039\/501100012659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>A novel fully automated chemiluminescent immunoassay (CLIA) has been developed to quantify autoantibodies specific for desmogleins (Dsg1, Dsg3), BP180, and BP230, key target antigens in pemphigus and bullous pemphigoid. This study aims to evaluate the diagnostic accuracy of the CLIA in diagnosing pemphigus and BP and its correlation with disease severity and clinical features.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Sera from 106 bullous pemphigoid and 54 pemphigus patients and control sera from 153 patients with other skin disease and 121 healthy volunteers were included. CLIA and BIOCHIP mosaic-based indirect immunofluorescence (IIFT-BIOCHIP) were performed for all bullous pemphigoid and pemphigus patients, with ELISA conducted for most. Disease severity was assessed using the Body Surface Area scoring.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>This CLIA showed strong agreement with IIFT-BIOCHIP, achieving area under the curve (AUC) values of 0.92 for anti-Dsg1\/anti-Dsg3 and 0.84 for anti-BP180\/anti-BP230 for differentiating pemphigus and BP. It outperformed ELISA (AUC: 0.73, 0.75) and was comparable to IIFT-BIOCHIP (AUC: 0.93, 0.87). The assay showed superior detection range and sensitivity compared to ELISA. Autoantibody levels correlated with disease severity and clinical symptoms, with elevated levels of anti-Dsg3 associated with mucosal lesions, anti-Dsg1\/anti-Dsg3 associated with Nikolsky sign, and elevated anti-BP180\/anti-BP230 levels linked to pruritus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The novel CLIA, the first to quantify four major autoimmune blister disease autoantibodies (anti-Dsg1\/anti-Dsg3\/anti-BP180\/anti-BP230) using a single sample tube, offers a simple and time-efficient test for diagnosing and screening pemphigus and BP. Its ability to assess disease severity and clinical relevance makes it a valuable tool for managing these conditions.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1576635","type":"journal-article","created":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T01:26:34Z","timestamp":1751246794000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Evaluation of a novel chemiluminescent immunoassay for autoantibody detection in pemphigus and bullous pemphigoid"],"prefix":"10.3389","volume":"16","author":[{"given":"Na","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanyu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luyang","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongwei","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxuan","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuping","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixia","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangming","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai-Zhou","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-012615-044313","article-title":"Mechanisms of disease: pemphigus and bullous pemphigoid","volume":"11","author":"Hammers","year":"2016","journal-title":"Annu Rev Pathol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.15770","article-title":"Validation of the BIOCHIP test for the diagnosis of bullous pemphigoid, pemphigus vulgaris and pemphigus foliaceus","volume":"34","author":"Yang","year":"2020","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1111\/1346-8138.12486","article-title":"Japanese guidelines for the management of pemphigus","volume":"41","author":"Amagai","year":"2014","journal-title":"J Dermatol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1111\/j.1346-8138.2011.01382.x","article-title":"Quality of life and psychological status of patients with pemphigus vulgaris using Dermatology Life Quality Index and General Health Questionnaires","volume":"39","author":"Ghodsi","year":"2012","journal-title":"J Dermatol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.clindermatol.2013.01.004","article-title":"Pemphigus: etiology, pathogenesis, and inducing or triggering factors: facts and controversies","volume":"31","author":"Ruocco","year":"2013","journal-title":"Clin Dermatol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1111\/ddg.12612","article-title":"S2k guideline for the diagnosis of pemphigus vulgaris\/foliaceus and bullous pemphigoid","volume":"13","author":"Schmidt","year":"2015","journal-title":"J Dtsch Dermatol Ges"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.18220","article-title":"Updated S2 K guidelines for the management of bullous pemphigoid initiated by the European Academy of Dermatology and Venereology (EADV)","volume":"36","author":"Borradori","year":"2022","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)61140-4","article-title":"Pemphigoid diseases","volume":"381","author":"Schmidt","year":"2013","journal-title":"Lancet"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.15679","article-title":"Review of autoimmune blistering diseases: the Pemphigoid diseases","volume":"33","author":"Daniel","year":"2019","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2014.01.011","article-title":"Diagnosis and classification of pemphigus and bullous pemphigoid","volume":"13","author":"Kershenovich","year":"2014","journal-title":"Autoimmun Rev"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1684\/ejd.2020.3839","article-title":"BIOCHIP mosaic for the diagnosis of autoimmune bullous diseases in Chinese patients","volume":"30","author":"Wang","year":"2020","journal-title":"Eur J Dermatol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1515\/cclm-2019-1031","article-title":"Detection of circulating anti-skin antibodies by indirect immunofluorescence and by ELISA: a comparative systematic review and meta-analysis","volume":"58","author":"Van de Gaer","year":"2020","journal-title":"Clin Chem Lab Med"},{"key":"B13","doi-asserted-by":"publisher","first-page":"11809","DOI":"10.3389\/bjbs.2023.11809","article-title":"Diagnostic techniques in autoimmune blistering diseases","volume":"80","author":"Mee","year":"2023","journal-title":"Br J BioMed Sci"},{"key":"B14","doi-asserted-by":"publisher","first-page":"2098","DOI":"10.3390\/diagnostics11112098","article-title":"Comparative analysis of BIOCHIP mosaic-based indirect immunofluorescence with enzyme-linked immunosorbent assay for diagnosing myasthenia gravis","volume":"11","author":"Gambino","year":"2021","journal-title":"Diagnostics (Basel)"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1363032","article-title":"State-of-the-art diagnosis of autoimmune blistering diseases","volume":"15","author":"van Beek","year":"2024","journal-title":"Front Immunol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2010.07.025","article-title":"Enhanced immunoassay sensitivity using chemiluminescent acridinium esters with increased light output","volume":"406","author":"Natrajan","year":"2010","journal-title":"Analytical Biochem"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(51)91975-7","article-title":"The exposure treatment of burns","volume":"1","author":"Wallace","year":"1951","journal-title":"Lancet"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1001\/jamadermatol.2013.8175","article-title":"Pemphigus disease activity measurements: pemphigus disease area index, autoimmune bullous skin disorder intensity score, and pemphigus vulgaris activity score","volume":"150","author":"Rahbar","year":"2014","journal-title":"JAMA Dermatol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.35541\/cjd.20240222","article-title":"Guidelines for diagnosis and treatment of pemphigus in China","volume":"57","year":"2024","journal-title":"Chin J Dermatol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2018.00296","article-title":"Diagnosis of autoimmune blistering diseases","volume":"5","author":"Witte","year":"2018","journal-title":"Front Med (Lausanne)"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.4103\/2229-5178.156386","article-title":"Role of direct immunofluorescence in dermatological disorders","volume":"6","author":"Mysorekar","year":"2015","journal-title":"Indian Dermatol Online J"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.4103\/0019-5154.135488","article-title":"A cross-sectional study of direct immunofluorescence in the diagnosis of immunobullous dermatoses","volume":"59","author":"Buch","year":"2014","journal-title":"Indian J Dermatol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/S0190-9622(94)70010-9","article-title":"The sensitivity and specificity of direct immunofluorescence testing in disorders of mucous membranes","volume":"30","author":"Helander","year":"1994","journal-title":"J Am Acad Dermatol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1159\/000368347","article-title":"Michel\u2019s transport medium as an alternative to liquid nitrogen for PCR analysis of skin biopsy specimens","volume":"1","author":"Boraiy","year":"2014","journal-title":"Dermatopathology (Basel)"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2133.2000.03538.x","article-title":"The use of two substrates to improve the sensitivity of indirect immunofluorescence in the diagnosis of pemphigus","volume":"142","author":"Harman","year":"2000","journal-title":"Br J Dermatol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.1992.tb00651.x","article-title":"Serological diagnosis of bullous pemphigoid (BP): comparison of the sensitivity of indirect immunofluorescence on salt-split skin to immunoblotting","volume":"126","author":"MaChado","year":"1992","journal-title":"Br J Dermatol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2013.07.009","article-title":"Comparative study of direct and indirect immunofluorescence and of bullous pemphigoid 180 and 230 enzyme-linked immunosorbent assays for diagnosis of bullous pemphigoid","volume":"69","author":"S\u00e1rdy","year":"2013","journal-title":"J Am Acad Dermatol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1186\/1750-1172-7-49","article-title":"Serological diagnosis of autoimmune bullous skin diseases: prospective comparison of the BIOCHIP mosaic-based indirect immunofluorescence technique with the conventional multi-step single test strategy","volume":"7","author":"van Beek","year":"2012","journal-title":"Orphanet J Rare Dis"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-3083.2007.02254.x","article-title":"Desmoglein 1 and 3 enzyme-linked immunosorbent assay in Iranian patients with pemphigus vulgaris: correlation with phenotype, severity, and disease activity","volume":"21","author":"Daneshpazhooh","year":"2007","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2016.12.007","article-title":"Validation of chemiluminescent enzyme immunoassay in detection of autoantibodies in pemphigus and pemphigoid","volume":"85","author":"Fujio","year":"2017","journal-title":"J Dermatol Sci"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1001\/jamadermatol.2024.3425","article-title":"Bullous pemphigoid severity and levels of antibodies to BP180 and BP230: A systematic review and meta-analysis","volume":"160","author":"Chou","year":"2024","journal-title":"JAMA Dermatol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2133.2001.04132.x","article-title":"The severity of cutaneous and oral pemphigus is related to desmoglein 1 and 3 antibody levels","volume":"144","author":"Harman","year":"2001","journal-title":"Br J Dermatol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2004.10.007","article-title":"Correlation of clinical severity and ELISA indices for the NC16A domain of BP180 measured using BP180 ELISA kit in bullous pemphigoid","volume":"37","author":"Tsuji-Abe","year":"2005","journal-title":"J Dermatol Sci"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1001\/archderm.1979.04010040006002","article-title":"Correlation of antibodies in skin and serum with disease severity in pemphigus","volume":"115","author":"Judd","year":"1979","journal-title":"Arch Dermatol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1001\/archderm.1966.01600230074020","article-title":"Clinical significance of autoantibodies in pemphigus","volume":"93","author":"Chorzelski","year":"1966","journal-title":"Arch Dermatol"},{"key":"B36","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1038\/jid.1968.94","article-title":"The immunopathology of pemphigus and bullous pemphigoid","volume":"51","author":"Beutner","year":"1968","journal-title":"J Invest Dermatol"},{"key":"B37","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1111\/j.1365-2133.1971.tb14190.x","article-title":"Correlation of pemphigoid and pemphigus antibody titres with activity of disease","volume":"84","author":"Sams","year":"1971","journal-title":"Br J Dermatol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12531752","article-title":"Comparison of different epithelial substrates useful for indirect immunofluorescence testing of sera from patients with active pemphigus","volume":"72","author":"Judd","year":"1979","journal-title":"J Invest Dermatol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2230.1981.tb02338.x","article-title":"Correlation of circulating intercellular antibody titres in pemphigus with disease activity","volume":"6","author":"Creswell","year":"1981","journal-title":"Clin Exp Dermatol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)31778-7","article-title":"Pemphigus","volume":"394","author":"Schmidt","year":"2019","journal-title":"Lancet"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2009.09266.x","article-title":"IgG autoantibody reactivity against bullous pemphigoid (BP) 180 and BP230 in elderly patients with pruritic dermatoses","volume":"161","author":"Feliciani","year":"2009","journal-title":"Br J Dermatol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1001\/jamadermatol.2018.4390","article-title":"Assessment of diagnostic strategy for early recognition of bullous and nonbullous variants of pemphigoid","volume":"155","author":"Meijer","year":"2019","journal-title":"JAMA Dermatol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.12936","article-title":"BP180- and BP230-specific IgG autoantibodies in pruritic disorders of the elderly: a preclinical stage of bullous pemphigoid","volume":"171","author":"Schmidt","year":"2014","journal-title":"Br J Dermatol"}],"updated-by":[{"DOI":"10.3389\/fimmu.2025.1661243","type":"corrigendum","label":"Corrigendum","source":"publisher","updated":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T00:00:00Z","timestamp":1753056000000}}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1576635\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T09:35:57Z","timestamp":1753090557000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1576635\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,30]]},"references-count":43,"alternative-id":["10.3389\/fimmu.2025.1576635"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1576635","relation":{"corrigendum":[{"id-type":"doi","id":"10.3389\/fimmu.2025.1661243","asserted-by":"object"}]},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,30]]},"article-number":"1576635"}}