Anti-Alpha-2-Macroglobulin-Like-1 Autoantibodies Are Detected Frequently and May Be Pathogenic in Paraneoplastic Pemphigus

DOI
Publisher DOI
PubMed ID
23407400
Abstract
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.
Date Issued
2013-07
Publication Type
Article
Subject(s)
Language(s)
en
Author(s)
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
Hashimoto, Takashi
Additional Credits
Journal
Journal of Investigative Dermatology
Publisher
Nature Publishing
ISSN
0022-202X
Access(Rights)
restricted
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