{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T08:59:03Z","timestamp":1790499543133,"version":"4.1.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2008,8,1]],"date-time":"2008-08-01T00:00:00Z","timestamp":1217548800000},"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":[[2008,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The autoimmune blistering skin disease pemphigus is caused by autoantibodies against keratinocyte surface Ags. In pemphigus vulgaris (PV), autoantibodies are primarily directed against desmosomal cadherins desmoglein (Dsg) 3 and Dsg 1, whereas pemphigus foliaceus (PF) patients only have Abs against Dsg 1. At present, it is unclear whether Dsg autoantibodies contribute to pemphigus pathogenesis by direct inhibition of Dsg transinteraction. Using atomic force microscopy, we provide evidence that PV-IgG directly interfere with homophilic Dsg 3 but, similar to PF-IgG, not with homophilic Dsg 1 transinteraction, indicating that the molecular mechanisms in PV and PF pathogenesis substantially differ. PV-IgG (containing Dsg 3 or Dsg 1 and Dsg 3 autoantibodies) as well as PV-IgG Fab reduced binding activity of Dsg 3 by \u223c60%, comparable to Ca2+ depletion. Similarly, the mouse monoclonal PV Ab AK 23 targeting the N-terminal Dsg 3 domain and AK 23 Fab reduced Dsg 3 transinteraction. In contrast, neither PV-IgG nor PF-IgG blocked Dsg 1 transinteraction. In HaCaT monolayers, however, both PV- and PF-IgG caused keratinocyte dissociation as well as loss of Dsg 1 and Dsg 3 transinteraction as revealed by laser tweezer assay. These data demonstrate that PV-IgG and PF-IgG reduce Dsg transinteraction by cell-dependent mechanisms and suggest that in addition, Abs to Dsg 3 contribute to PV by direct inhibition of Dsg transinteraction.<\/jats:p>","DOI":"10.4049\/jimmunol.181.3.1825","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T19:00:52Z","timestamp":1397847652000},"page":"1825-1834","source":"Crossref","is-referenced-by-count":126,"title":["Pemphigus Vulgaris IgG Directly Inhibit Desmoglein 3-Mediated Transinteraction"],"prefix":"10.1093","volume":"181","author":[{"given":"Wolfgang-Moritz","family":"Heupel","sequence":"first","affiliation":[{"name":"Department of Anatomy and Cell Biology, University of W\u00fcrzburg , W\u00fcrzburg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Detlef","family":"Zillikens","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of L\u00fcbeck , L\u00fcbeck,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Detlev","family":"Drenckhahn","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, University of W\u00fcrzburg , W\u00fcrzburg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Waschke","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, University of W\u00fcrzburg , W\u00fcrzburg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2008,8,1]]},"reference":[{"key":"2026012806190142400_R1","first-page":"61","article-title":"Pemphigus","volume-title":"Lancet","year":"2005"},{"key":"2026012806190142400_R2","first-page":"1800","article-title":"Pemphigus, bullous impetigo, and the staphylococcal scalded-skin syndrome","volume-title":"N. Engl. J. Med.","year":"2006"},{"key":"2026012806190142400_R3","first-page":"1189","article-title":"Induction of pemphigus in neonatal mice by passive transfer of IgG from patients with the disease","volume-title":"N. Engl. J. Med.","year":"1982"},{"key":"2026012806190142400_R4","first-page":"505","article-title":"Demonstration of skin antibodies in sera of pemphigus vulgaris patients by indirect immunofluorescent staining","volume-title":"Proc. Soc. Exp. Biol. Med.","year":"1964"},{"key":"2026012806190142400_R5","first-page":"254","article-title":"Production of epidermal acantholysis in normal human skin in vitro by the IgG fraction from pemphigus serum","volume-title":"J. Invest. Dermatol.","year":"1976"},{"key":"2026012806190142400_R6","first-page":"869","article-title":"Autoantibodies against a novel epithelial cadherin in pemphigus vulgaris, a disease of cell adhesion","volume-title":"Cell","year":"1991"},{"key":"2026012806190142400_R7","first-page":"807","article-title":"Identification of pemphigus vulgaris antigen extracted from normal human epidermis and comparison with pemphigus foliaceus antigen","volume-title":"J. Clin. Invest.","year":"1988"},{"key":"2026012806190142400_R8","first-page":"1","article-title":"Identification of desmoglein, a constitutive desmosomal glycoprotein, as a member of the cadherin family of cell adhesion molecules","volume-title":"Eur. J. Cell Biol.","year":"1990"},{"key":"2026012806190142400_R9","first-page":"313","article-title":"Distinction between epidermal antigens binding pemphigus vulgaris and pemphigus foliaceus autoantibodies","volume-title":"J. Clin. Invest.","year":"1984"},{"key":"2026012806190142400_R10","first-page":"1377","article-title":"Novel human \u03b19 acetylcholine receptor regulating keratinocyte adhesion is targeted by pemphigus vulgaris autoimmunity","volume-title":"Am. J. Pathol.","year":"2000"},{"key":"2026012806190142400_R11","first-page":"29466","article-title":"Pemphigus vulgaris antibody identifies pemphaxin: a novel keratinocyte annexin-like molecule binding acetylcholine","volume-title":"J. Biol. Chem.","year":"2000"},{"key":"2026012806190142400_R12","first-page":"1467","article-title":"Antibodies against keratinocyte antigens other than desmogleins 1 and 3 can induce pemphigus vulgaris-like lesions","volume-title":"J. Clin. Invest.","year":"2000"},{"key":"2026012806190142400_R13","first-page":"815","article-title":"Are desmoglein autoantibodies essential for the immunopathogenesis of pemphigus vulgaris, or just \u201cwitnesses of disease\u201d?","volume-title":"Exp. Dermatol.","year":"2006"},{"key":"2026012806190142400_R14","first-page":"990","article-title":"Pemphigus: an unfolding story","volume-title":"J. Invest. Dermatol.","year":"2001"},{"key":"2026012806190142400_R15","first-page":"536","article-title":"Desmosomes and disease: pemphigus and bullous impetigo","volume-title":"Curr. Opin. Cell Biol.","year":"2004"},{"key":"2026012806190142400_R16","first-page":"167","article-title":"The clinical phenotype of pemphigus is defined by the anti-desmoglein autoantibody profile","volume-title":"J. Am. Acad. Dermatol.","year":"1999"},{"key":"2026012806190142400_R17","first-page":"592","article-title":"Mucosal and mucocutaneous (generalized) pemphigus vulgaris show distinct autoantibody profiles","volume-title":"J. Invest. Dermatol.","year":"1997"},{"key":"2026012806190142400_R18","first-page":"976","article-title":"Antibodies to desmoglein 1 and 3, and the clinical phenotype of pemphigus vulgaris","volume-title":"J. Am. Acad. Dermatol.","year":"2003"},{"key":"2026012806190142400_R19","first-page":"541","article-title":"A comparison of anti-desmoglein antibodies and indirect immunofluorescence in the serodiagnosis of pemphigus vulgaris","volume-title":"Int. J. Dermatol.","year":"2005"},{"key":"2026012806190142400_R20","first-page":"2170","article-title":"Induction of pemphigus phenotype by a mouse monoclonal antibody against the amino-terminal adhesive interface of desmoglein 3","volume-title":"J. Immunol.","year":"2003"},{"key":"2026012806190142400_R21","first-page":"1308","article-title":"C-cadherin ectodomain structure and implications for cell adhesion mechanisms","volume-title":"Science","year":"2002"},{"key":"2026012806190142400_R22","first-page":"327","article-title":"Structural basis of cell-cell adhesion by cadherins","volume-title":"Nature","year":"1995"},{"key":"2026012806190142400_R23","first-page":"5439","article-title":"Dominant autoimmune epitopes recognized by pemphigus antibodies map to the N-terminal adhesive region of desmogleins","volume-title":"J. Immunol.","year":"2001"},{"key":"2026012806190142400_R24","first-page":"3157","article-title":"Pemphigus foliaceus IgG causes dissociation of desmoglein 1-containing junctions without blocking desmoglein 1 transinteraction","volume-title":"J. Clin. Invest.","year":"2005"},{"key":"2026012806190142400_R25","first-page":"126","article-title":"Fluorescence detection of calcium-binding proteins with quinoline Ca-indicator quin2","volume-title":"Anal. Biochem.","year":"1997"},{"key":"2026012806190142400_R26","first-page":"3477","article-title":"Detection and localization of individual antibody-antigen recognition events by atomic force microscopy","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1996"},{"key":"2026012806190142400_R27","first-page":"4005","article-title":"Cadherin interaction probed by atomic force microscopy","volume-title":"Proc. Natl. Acad. Sci. USA","year":"2000"},{"key":"2026012806190142400_R28","first-page":"906","article-title":"Pemphigus IgG causes skin splitting in the presence of both desmoglein 1 and desmoglein 3","volume-title":"Am. J. Pathol.","year":"2007"},{"key":"2026012806190142400_R29","first-page":"721","article-title":"Inhibition of Rho A activity causes pemphigus skin blistering","volume-title":"J. Cell Biol.","year":"2006"},{"key":"2026012806190142400_R30","first-page":"17866","article-title":"Anti-desmoglein 3 (Dsg3) monoclonal antibodies deplete desmosomes of Dsg3 and differ in their Dsg3-depleting activities related to pathogenicity","volume-title":"J. Biol. Chem.","year":"2007"},{"key":"2026012806190142400_R31","first-page":"895","article-title":"Antigen-specific immunoadsorption of pathogenic autoantibodies in pemphigus foliaceus","volume-title":"J. Invest. Dermatol.","year":"1995"},{"key":"2026012806190142400_R32","first-page":"383","article-title":"Calcium-dependent conformation of desmoglein 1 is required for its cleavage by exfoliative toxin","volume-title":"J. Invest. Dermatol.","year":"2003"},{"key":"2026012806190142400_R33","first-page":"461","article-title":"Explanations for the clinical and microscopic localization of lesions in pemphigus foliaceus and vulgaris","volume-title":"J. Clin. Invest.","year":"1999"},{"key":"2026012806190142400_R34","first-page":"1","article-title":"Beyond steric hindrance: the role of adhesion signaling pathways in the pathogenesis of pemphigus","volume-title":"J. Dermatol. Sci.","year":"2007"},{"key":"2026012806190142400_R35","first-page":"419","article-title":"Coordinated expression of desmoglein 1 and desmocollin 1 regulates intercellular adhesion","volume-title":"Differentiation","year":"2004"},{"key":"2026012806190142400_R36","first-page":"495","article-title":"Coexpression of both types of desmosomal cadherin and plakoglobin confers strong intercellular adhesion","volume-title":"J. Cell Sci.","year":"1998"},{"key":"2026012806190142400_R37","first-page":"S37","article-title":"Loss of desmocollin 3 in the epidermis of mice causes epidermal blistering and telogen hair loss","volume-title":"J. Invest. Dermatol.","year":"2007"},{"key":"2026012806190142400_R38","first-page":"12855","article-title":"p38MAPK inhibition prevents disease in pemphigus vulgaris mice","volume-title":"Proc. Natl. Acad. Sci. USA","year":"2006"},{"key":"2026012806190142400_R39","first-page":"823","article-title":"A central role for the armadillo protein plakoglobin in the autoimmune disease pemphigus vulgaris","volume-title":"J. Cell Biol.","year":"2001"},{"key":"2026012806190142400_R40","first-page":"13804","article-title":"Desmoglein versus non-desmoglein signaling in pemphigus acantholysis: characterization of novel signaling pathways downstream of pemphigus vulgaris antigens","volume-title":"J. Biol. Chem.","year":"2007"},{"key":"2026012806190142400_R41","first-page":"137","article-title":"Transmembrane signaling for adhesive regulation of desmosomes and hemidesmosomes, and for cell-cell detachment induced by pemphigus IgG in cultured keratinocytes: involvement of protein kinase C","volume-title":"J. Investig. Dermatol. Symp. Proc.","year":"1999"},{"key":"2026012806190142400_R42","first-page":"3298","article-title":"Pemphigus vulgaris identifies plakoglobin as key suppressor of c-Myc in the skin","volume-title":"EMBO J.","year":"2006"},{"key":"2026012806190142400_R43","first-page":"21","article-title":"The desmosome and pemphigus","volume-title":"Histochem. Cell Biol.","year":"2008"},{"key":"2026012806190142400_R44","first-page":"S34","article-title":"Autoantibodies in the autoimmune disease pemphigus foliaceus induce blistering in vivo via p38MAPK-dependent signaling","volume-title":"J. Invest. Dermatol.","year":"2007"},{"key":"2026012806190142400_R45","first-page":"33","article-title":"Pemphigus IgG, but not bullous pemphigoid IgG, causes a transient increase in intracellular calcium and inositol 1,4,5-triphosphate in DJM-1 cells, a squamous cell carcinoma line","volume-title":"J. Invest. Dermatol.","year":"1995"},{"key":"2026012806190142400_R46","first-page":"23778","article-title":"Desmosome signaling: inhibition of p38MAPK prevents pemphigus vulgaris IgG-induced cytoskeleton reorganization","volume-title":"J. Biol. Chem.","year":"2005"},{"key":"2026012806190142400_R47","first-page":"587","article-title":"Pathogenic monoclonal antibody against desmoglein 3 augments desmoglein 3 and p38 MAPK phosphorylation in human squamous carcinoma cell line","volume-title":"Autoimmunity","year":"2006"},{"key":"2026012806190142400_R48","first-page":"2135","article-title":"Pemphigus vulgaris IgG and methylprednisolone exhibit reciprocal effects on keratinocytes","volume-title":"J. Biol. Chem.","year":"2004"},{"key":"2026012806190142400_R49","first-page":"265","article-title":"Cholinergic control of epidermal cohesion","volume-title":"Exp. Dermatol.","year":"2006"},{"key":"2026012806190142400_R50","first-page":"1091","article-title":"Targeted disruption of the pemphigus vulgaris antigen (desmoglein 3) gene in mice causes loss of keratinocyte cell adhesion with a phenotype similar to pemphigus vulgaris","volume-title":"J. Cell Biol.","year":"1997"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/181\/3\/1825\/62578713\/7527.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/181\/3\/1825\/62578713\/7527.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T11:19:08Z","timestamp":1769599148000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/181\/3\/1825\/8003179"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,8,1]]},"references-count":50,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2008,8,1]]},"published-print":{"date-parts":[[2008,8,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.181.3.1825","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1126020.584107","asserted-by":"object"}]},"ISSN":["1550-6606","0022-1767"],"issn-type":[{"value":"1550-6606","type":"electronic"},{"value":"0022-1767","type":"print"}],"subject":[],"published-other":{"date-parts":[[2008,8]]},"published":{"date-parts":[[2008,8,1]]}}}