Anti-Alpha-2-Macroglobulin-Like-1 Autoantibodies Are Detected Frequently and May Be Pathogenic in Paraneoplastic Pemphigus
Data(s) |
01/07/2013
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Resumo |
Paraneoplastic pemphigus (PNP) shows autoantibodies mainly to plakin and desmosomal cadherin family proteins. We have recently identified alpha-2-macroglobulin-like-1 (A2ML1), a broad range protease inhibitor, as a unique PNP antigen. In this study, we tested a large number of PNP sera by various methods. Forty (69.0%) of 58 PNP sera recognized A2ML1 recombinant protein expressed in COS7 cells by immunofluorescence (IF) and/or immunoprecipitation (IP)/immunoblotting (IB). IP/IB showed higher sensitivity than IF. In addition, 22 (37.9%) PNP sera reacted with A2ML1 by IB of cultured normal human keratinocytes (NHKs) under non-reducing conditions. Statistical analyses using various clinical and immunological data showed that the presence of anti-A2ML1 autoantibodies was associated with early disease onset and absence of ocular lesions. Next, to investigate the pathogenic role of anti-A2ML1 antibody, we performed additional functional studies. Addition of anti-A2ML1 polyclonal antibody to culture media decreased NHK cell adhesion examined by dissociation assay, and increased plasmin activity detected by casein zymography, suggesting that anti-A2ML1 antibody may decrease NHK cell adhesion through plasmin activation by inhibition of A2ML1. This study demonstrates that autoantibodies to A2ML1 are frequently and specifically detected and may have a pathogenic role in PNP. |
Formato |
application/pdf |
Identificador |
http://boris.unibe.ch/45624/1/jid201365a.pdf Numata, Sanae; Teye, Kwesi; Tsuruta, Daisuke; Sogame, Ryosuke; Ishii, Norito; Koga, Hiroshi; Natsuaki, Yohei; Tsuchisaka, Atsunari; Hamada, Takahiro; Karashima, Tadashi; Nakama, Takekuni; Furumura, Minao; Ohata, Chika; Kawakami, Tamihiro; Schepens, Isabelle; Borradori, Luca; Hashimoto, Takashi (2013). Anti-Alpha-2-Macroglobulin-Like-1 Autoantibodies Are Detected Frequently and May Be Pathogenic in Paraneoplastic Pemphigus. Journal of Investigative Dermatology, 133(7), pp. 1785-1793. Nature Publishing 10.1038/jid.2013.65 <http://dx.doi.org/10.1038/jid.2013.65> doi:10.7892/boris.45624 info:doi:10.1038/jid.2013.65 info:pmid:23407400 urn:issn:0022-202X |
Idioma(s) |
eng |
Publicador |
Nature Publishing |
Relação |
http://boris.unibe.ch/45624/ |
Direitos |
info:eu-repo/semantics/restrictedAccess |
Fonte |
Numata, Sanae; Teye, Kwesi; Tsuruta, Daisuke; Sogame, Ryosuke; Ishii, Norito; Koga, Hiroshi; Natsuaki, Yohei; Tsuchisaka, Atsunari; Hamada, Takahiro; Karashima, Tadashi; Nakama, Takekuni; Furumura, Minao; Ohata, Chika; Kawakami, Tamihiro; Schepens, Isabelle; Borradori, Luca; Hashimoto, Takashi (2013). Anti-Alpha-2-Macroglobulin-Like-1 Autoantibodies Are Detected Frequently and May Be Pathogenic in Paraneoplastic Pemphigus. Journal of Investigative Dermatology, 133(7), pp. 1785-1793. Nature Publishing 10.1038/jid.2013.65 <http://dx.doi.org/10.1038/jid.2013.65> |
Palavras-Chave | #610 Medicine & health |
Tipo |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion PeerReviewed |