{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T11:11:34Z","timestamp":1760267494052,"version":"3.37.3"},"reference-count":56,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T00:00:00Z","timestamp":1736121600000},"content-version":"vor","delay-in-days":2715,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["immunohorizons.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2017,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>We have shown that although the IgG response in fogo selvagem (FS) is mainly restricted to desmoglein (Dsg) 1, other keratinocyte cadherins are also targeted by FS patients and healthy control subjects living in the endemic region of Lim\u00e3o Verde, Brazil (endemic controls). Evaluating nonpathogenic IgG1 and pathogenic IgG4 subclass responses to desmosomal proteins may reveal important differences between pathogenic and nonpathogenic responses, and how these differences relate to the pathogenic IgG4 response and resultant FS. In this study, we tested by ELISA &amp;gt;100 sera from each FS patient, endemic control, and nonendemic control for IgG1 and IgG4 autoantibodies to keratinocyte cadherins besides Dsg1. IgG1 and IgG4 subclass responses in endemic controls are highly correlated between Dsg1 and other keratinocyte cadherins. This correlation persists in the IgG1 response among FS patients, but diminishes in IgG4 response, suggesting that IgG1 binds highly conserved linear epitopes among cadherins, whereas IgG4 binds mainly specific conformational epitopes on Dsg1. A confirmatory test comparing serum samples of 11 individuals before and after their FS onset substantiated our findings that IgG1 recognizes primarily linear epitopes on Dsg1 both before and after disease onset, whereas IgG4 recognizes primarily linear epitopes before disease onset, but recognizes more conformational epitopes on Dsg1 after the onset of disease. This study may provide a mechanism by which a specificity convergence of the IgG4 response to unique Dsg1 epitopes, most likely conformational pathogenic epitopes, leads to the onset of FS disease.<\/jats:p>","DOI":"10.4049\/immunohorizons.1700029","type":"journal-article","created":{"date-parts":[[2017,8,2]],"date-time":"2017-08-02T01:00:29Z","timestamp":1501635629000},"page":"71-80","update-policy":"https:\/\/doi.org\/10.4049\/immunohorizon.f110.005975","source":"Crossref","is-referenced-by-count":5,"title":["Divergent Specificity Development of IgG1 and IgG4 Autoantibodies in Endemic Pemphigus Foliaceus (Fogo Selvagem)"],"prefix":"10.1093","volume":"1","author":[{"given":"Mike","family":"Maldonado","sequence":"first","affiliation":[{"name":"Department of Dermatology, University of North Carolina at Chapel Hill , Chapel Hill, NC 27599"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis A","family":"Diaz","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of North Carolina at Chapel Hill , Chapel Hill, NC 27599"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Phillip","family":"Prisayanh","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of North Carolina at Chapel Hill , Chapel Hill, NC 27599"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinsheng","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of North Carolina at Chapel Hill , Chapel Hill, NC 27599"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bahjat F","family":"Qaqish","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, University of North Carolina at Chapel Hill , Chapel Hill, NC 27599"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valeria","family":"Aoki","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Sao Paulo Medical School , Sao Paulo, CEP-05403-002 ,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gunter","family":"Hans-Filho","sequence":"additional","affiliation":[{"name":"Departamento de Dermatologia, Universidade Federal de Mato Grosso do Sul , Campo Grande, Mato Grosso do Sul, 79002212 ,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evandro A","family":"Rivitti","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Sao Paulo Medical School , Sao Paulo, CEP-05403-002 ,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donna A","family":"Culton","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of North Carolina at Chapel Hill , Chapel Hill, NC 27599"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0731-5596","authenticated-orcid":false,"given":"Ye","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of North Carolina at Chapel Hill , Chapel Hill, NC 27599"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2017,8,1]]},"reference":[{"key":"2025010608402729800_r1","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1111\/1523-1747.ep12298213","article-title":"An active focus of high prevalence of fogo selvagem on an Amerindian reservation in Brazil","volume":"107","author":"Hans-Filho","year":"1996","journal-title":"J. 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Dermatol."},{"key":"2025010608402729800_r3","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1111\/j.1399-0039.1997.tb02707.x","article-title":"An epitope in the third hypervariable region of the DRB1 gene is involved in the susceptibility to endemic pemphigus foliaceus (fogo selvagem) in three different Brazilian populations","volume":"49","author":"Moraes","year":"1997","journal-title":"Tissue Antigens"},{"key":"2025010608402729800_r4","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1016\/j.autrev.2016.07.005","article-title":"Non-infectious environmental antigens as a trigger for the initiation of an autoimmune skin disease","volume":"15","author":"Qian","year":"2016","journal-title":"Autoimmun. 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