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Peripheral blood mononuclear cells (PBMC) from a total of 28 bullous pemphigoid patients and 14 matched controls were tested for proliferative and cytokine responses to recombinant NC16a and a complete panel of 21 overlapping peptides spanning this region of BP180. Proliferative responses to NC16A and the peptide panel in the patients with active disease were similar in frequency and magnitude to those in healthy donors, and included late responses typical of naive cells in approximately 60% of each group. Interleukin (IL)-4 responses were slightly stronger for six peptides, and significantly stronger for Nc16a, in patients than in controls. Factor analysis identified factors that separate responses to the peptide panel discretely into IL-4, T helper type 2 (Th2) pattern, interferon (IFN)-\u03b3, Th1 pattern and IL-10 or transforming growth factor [TGF-\u03b2, regulatory T cell (Treg)] pattern. Factors segregating IL-10 versus\u2005IFN-\u03b3 were predicted by active blistering or remission, and TGF-\u03b2 or IL-10 versus\u2005IFN-\u03b3 by age. Finally, we confirmed a significant up-regulation of IgE responses to BP180 in the patients with pemphigoid. This shows the complexity of T cell phenotype and fine autoreactive specificity in responses to NC16A, in patients and in normal controls. Important disease-associated factors determine the balance of cytokine responses. Of these, specific IL-4 and IgE responses show the strongest associations with pemphigoid, pointing to an important contribution by Th2 cytokines to pathogenesis.<\/jats:p>","DOI":"10.1111\/cei.12566","type":"journal-article","created":{"date-parts":[[2014,12,5]],"date-time":"2014-12-05T23:44:36Z","timestamp":1417823076000},"page":"189-200","source":"Crossref","is-referenced-by-count":32,"title":["T cell participation in autoreactivity to NC16a epitopes in bullous pemphigoid"],"prefix":"10.1093","volume":"180","author":[{"given":"W J","family":"Pickford","sequence":"first","affiliation":[{"name":"The Division of Applied Medicine, Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V","family":"Gudi","sequence":"additional","affiliation":[{"name":"West Suffolk Hospitals NHS Trust, Ipswich, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A M","family":"Haggart","sequence":"additional","affiliation":[{"name":"The Division of Applied Medicine, Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B J","family":"Lewis","sequence":"additional","affiliation":[{"name":"The Division of Applied Medicine, Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Herriot","sequence":"additional","affiliation":[{"name":"Department of Immunology, Aberdeen Royal Infirmary, Aberdeen, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R N","family":"Barker","sequence":"additional","affiliation":[{"name":"The Division of Applied Medicine, Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A D","family":"Ormerod","sequence":"additional","affiliation":[{"name":"The Division of Applied Medicine, Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,4,14]]},"reference":[{"key":"2021122010133848600_cei12566-bib-0001","first-page":"545","volume-title":"The auto-immune diseases","author":"Lin","year":"1998"},{"key":"2021122010133848600_cei12566-bib-0002","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1111\/j.1365-2133.2005.06662.x","article-title":"Annual incidence and mortality of bullous pemphigoid in the Grampian Region of North-east Scotland","volume":"153","author":"Gudi","year":"2005","journal-title":"Br J Dermatol"},{"key":"2021122010133848600_cei12566-bib-0003","doi-asserted-by":"crossref","first-page":"1998","DOI":"10.1038\/jid.2012.35","article-title":"Incidence and mortality of bullous pemphigoid in France","volume":"132","author":"Joly","year":"2012","journal-title":"J Invest Dermatol"},{"key":"2021122010133848600_cei12566-bib-0004","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1111\/j.1365-2133.2008.08858.x","article-title":"IgE autoantibodies against the intracellular domain of BP180","volume":"160","author":"Dresow","year":"2009","journal-title":"Br J Dermatol"},{"key":"2021122010133848600_cei12566-bib-0005","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1111\/1523-1747.ep13070476","article-title":"A 230-kD basic protein is the major bullous pemphigoid antigen","volume":"92","author":"Mueller","year":"1989","journal-title":"J Invest Dermatol"},{"key":"2021122010133848600_cei12566-bib-0006","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1172\/JCI114812","article-title":"Isolation of a human epidermal cDNA corresponding to the 180-kD autoantigen recognized by bullous pemphigoid and herpes gestationis sera. 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