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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Pathogenic anti-desmoglein 3 mAbs cloned from a paraneoplastic pemphigus patient by phage display
Journal of Investigative Dermatology, Volume 132, No. 4, Year 2012
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Description
Paraneoplastic pemphigus (PNP) is an autoimmune blistering disease associated with lymphoproliferative neoplasms and characterized by antibodies against plakins and desmoglein 3 (Dsg3). Anti-Dsg3 antibodies have a primary role in blister formation in PNP. In this study, we used phage display to clone monoclonal anti-Dsg3 antibodies from a PNP patient to further characterize their pathogenicity. We isolated 20 unique Dsg3-reactive mAbs, which we classified into four groups according to the heavy-chain complementarity-determining region 3 (CDR3) region. Genetic analyses demonstrated that three antibody groups used the VH1-46 gene (18 clones) and one group used the VH1-02 gene (2 clones). The results of an in vitro keratinocyte dissociation assay and a human skin organ culture injection assay showed that three antibodies displayed pathogenic activity in blister formation with different potencies. Epitope mapping using domain-swapped Dsg3/Dsg2 showed that these pathogenic mAbs bound Ca2+ -dependent conformational epitopes in the middle portion of the extracellular region of Dsg3 (EC2 and EC3 domains), in contrast to most previously characterized pathogenic pemphigus vulgaris antibodies, which bound to the EC1 domain of Dsg3. These mAbs reflect the unique polyclonal nature of anti-Dsg3 antibodies in PNP and represent an important tool for detailing the pathophysiological mechanisms of blister formation in PNP. © 2012 The Society for Investigative Dermatology.
Authors & Co-Authors
Saleh, Marwah Adly
Japan, Tokyo
Keio University
Egypt, Cairo
Faculty of Medicine
Ishii, Ken
Japan, Tokyo
Keio University
Japan, Ichihara
Teikyo University Chiba Medical Center
Yamagami, Jun
Japan, Tokyo
Keio University
Shirakata, Yuji
Japan, Toon
Ehime University School of Medicine
Hashimoto, Koji
Japan, Toon
Ehime University School of Medicine
Amagai, Masayuki
Japan, Tokyo
Keio University
Statistics
Citations: 26
Authors: 6
Affiliations: 4
Identifiers
Doi:
10.1038/jid.2011.449
ISSN:
0022202X
e-ISSN:
15231747
Research Areas
Genetics And Genomics
Health System And Policy