{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T03:22:28Z","timestamp":1791256948143,"version":"4.1.0"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2011,7,1]],"date-time":"2011-07-01T00:00:00Z","timestamp":1309478400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Bullous pemphigoid (BP) is a subepidermal blistering disease characterized by IgE and IgG class autoantibodies specific for 180-kDa BP Ag 2 (BP180), a protein involved in cell-substrate attachment. Although some direct effects of BP IgG have been observed on keratinocytes, no study to date has examined direct effects of BP IgE. In this study, we use primary cultures of human keratinocytes to demonstrate Ag-specific binding and internalization of BP IgE. Moreover, when BP IgE and BP IgG were compared, both isotypes stimulated FcR- independent production of IL-6 and IL-8, cytokines critical for BP pathology, and elicited changes in culture confluence and viability. We then used a human skin organ culture model to test the direct effects of these Abs on the skin, whereas excluding the immune inflammatory processes that are triggered by these Abs. In these experiments, physiologic concentrations of BP IgE and BP IgG exerted similar effects on human skin by stimulating IL-6 and IL-8 production and decreasing the number of hemidesmosomes localized at the basement membrane zone. We propose that the Ab-mediated loss of hemidesmosomes could weaken attachment of basal keratinocytes to the basement membrane zone of affected skin, thereby contributing to blister formation. In this article, we identify a novel role for IgE class autoantibodies in BP mediated through an interaction with BP180 on the keratinocyte surface. In addition, we provide evidence for an FcR-independent mechanism for both IgE and IgG class autoantibodies that could contribute to BP pathogenesis.<\/jats:p>","DOI":"10.4049\/jimmunol.1001753","type":"journal-article","created":{"date-parts":[[2011,6,7]],"date-time":"2011-06-07T00:54:41Z","timestamp":1307408081000},"page":"553-560","source":"Crossref","is-referenced-by-count":77,"title":["FcR-Independent Effects of IgE and IgG Autoantibodies in Bullous Pemphigoid"],"prefix":"10.1093","volume":"187","author":[{"given":"Kelly N","family":"Messingham","sequence":"first","affiliation":[{"name":"Department of Dermatology, University of Iowa , Iowa City, IA 52242"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rupasree","family":"Srikantha","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Iowa , Iowa City, IA 52242"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy M","family":"DeGueme","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Medical College of Wisconsin , Milwaukee, WI 53226"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet A","family":"Fairley","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Iowa , Iowa City, IA 52242"},{"name":"Department of Veterans Affairs , Iowa City, IA 52240"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2011,7,1]]},"reference":[{"key":"2025032410184986500_r1","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1001\/jama.1967.03120220053008","article-title":"Basement zone antibodies in bullous pemphigoid","volume":"200","author":"Jordon","year":"1967","journal-title":"JAMA"},{"key":"2025032410184986500_r2","doi-asserted-by":"crossref","first-page":"145","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":"2025032410184986500_r3","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1001\/archderm.136.2.174","article-title":"Serum levels of autoantibodies to BP180 correlate with disease activity in patients with bullous pemphigoid","volume":"136","author":"Schmidt","year":"2000","journal-title":"Arch. Dermatol."},{"key":"2025032410184986500_r4","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/S0923-1811(00)00149-3","article-title":"Clinical significance of enzyme-linked immunosorbent assay for the detection of circulating anti-BP180 autoantibodies in patients with bullous pemphigoid","volume":"26","author":"Amo","year":"2001","journal-title":"J. Dermatol. 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Autoimmun."},{"key":"2025032410184986500_r8","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1172\/JCI200521386","article-title":"Induction of dermal-epidermal separation in mice by passive transfer of antibodies specific to type VII collagen","volume":"115","author":"Sitaru","year":"2005","journal-title":"J. Clin. Invest."},{"key":"2025032410184986500_r9","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1046\/j.1523-1747.2002.01720.x","article-title":"Autoantibodies to bullous pemphigoid antigen 180 induce dermal-epidermal separation in cryosections of human skin","volume":"118","author":"Sitaru","year":"2002","journal-title":"J. Invest. 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Dermatol."},{"key":"2025032410184986500_r32","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1007\/BF02507102","article-title":"Detection of elevated levels of IL-4, IL-6, and IL-10 in blister fluid of bullous pemphigoid","volume":"288","author":"Schmidt","year":"1996","journal-title":"Arch. Dermatol. Res."},{"key":"2025032410184986500_r33","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1046\/j.1365-2133.1998.02028.x","article-title":"Internalization of the 180 kDa bullous pemphigoid antigen as immune complexes in basal keratinocytes: an important early event in blister formation in bullous pemphigoid","volume":"138","author":"Kitajima","year":"1998","journal-title":"Br. J. Dermatol."},{"key":"2025032410184986500_r34","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1038\/jid.2008.305","article-title":"IgG from patients with bullous pemphigoid depletes cultured keratinocytes of the 180-kDa bullous pemphigoid antigen (type XVII collagen) and weakens cell attachment","volume":"129","author":"Iwata","year":"2009","journal-title":"J. Invest. Dermatol."},{"key":"2025032410184986500_r35","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1172\/JCI117785","article-title":"180-kD bullous pemphigoid antigen (BP180) is deficient in generalized atrophic benign epidermolysis bullosa","volume":"95","author":"Jonkman","year":"1995","journal-title":"J. Clin. Invest."},{"key":"2025032410184986500_r36","first-page":"189","article-title":"Effects of all-trans retinoic acid and Ca++ on human skin in organ culture","volume":"142","author":"Varani","year":"1993","journal-title":"Am. J. Pathol."},{"key":"2025032410184986500_r37","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1001\/archdermatol.2007.9","article-title":"Correlation of IgE autoantibody to BP180 with a severe form of bullous pemphigoid","volume":"144","author":"Iwata","year":"2008","journal-title":"Arch. Dermatol."},{"key":"2025032410184986500_r38","doi-asserted-by":"crossref","first-page":"8821","DOI":"10.1021\/bi970675n","article-title":"A recombinant form of the human BP180 ectodomain forms a collagen-like homotrimeric complex","volume":"36","author":"Balding","year":"1997","journal-title":"Biochemistry"},{"key":"2025032410184986500_r39","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1159\/000246928","article-title":"A possible cell-biologic mechanism involved in blister formation of bullous pemphigoid: anti-180-kD BPA antibody is an initiator","volume":"189","author":"Kitajima","year":"1994","journal-title":"Dermatology (Basel)"},{"key":"2025032410184986500_r40","first-page":"193","article-title":"Immunopathology of bullous pemphigoid. Basement membrane deposition of IgE, alternate pathway components and fibrin","volume":"18","author":"Provost","year":"1974","journal-title":"Clin. Exp. Immunol."},{"key":"2025032410184986500_r41","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1046\/j.1365-2133.1998.02261.x","article-title":"Precise ultrastructural localization of in vivo deposited IgG antibodies in fresh perilesional skin of patients with bullous pemphigoid","volume":"138","author":"Sato","year":"1998","journal-title":"Br. J. Dermatol."},{"key":"2025032410184986500_r42","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1046\/j.1365-2249.2001.01503.x","article-title":"The IL-8 release from cultured human keratinocytes, mediated by antibodies to bullous pemphigoid autoantigen 180, is inhibited by dapsone","volume":"124","author":"Schmidt","year":"2001","journal-title":"Clin. Exp. 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Dermatol."},{"key":"2025032410184986500_r49","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1111\/1523-1747.ep12345821","article-title":"A homozygous deletion mutation in the gene encoding the 180-kDa bullous pemphigoid antigen (BPAG2) in a family with generalized atrophic benign epidermolysis bullosa","volume":"106","author":"McGrath","year":"1996","journal-title":"J. Invest. 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