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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Pathogenic epitopes of autoantibodies in pemphigus reside in the amino-terminal adhesive region of desmogleins which are unmasked by proteolytic processing of prosequence
Journal of Investigative Dermatology, Volume 129, No. 9, Year 2009
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Description
Pemphigus targets desmogleins (Dsgs), which are thought to be synthesized as inactive precursor proteins with prosequences that are cleaved by substilisin-like proprotein convertases, such as furin, to yield mature adhesive molecules. We hypothesized that some pemphigus pathogenic antibodies (Abs), which presumably interfere with adhesion, only bind the mature form. A pathogenic and three non-pathogenic anti-Dsg1 monoclonal Abs (mAbs) isolated from a pemphigus foliaceus (PF) patient, were used for immunoprecipitation and ELISA of recombinant precursor and mature Dsg1. The pathogenic Ab binds mature Dsg1, whereas non-pathogenic Abs bind either only the precursor or both the precursor and mature Dsg1. Competition ELISA showed that the majority of PF sera target the same or nearby epitopes defined by the pathogenic anti-Dsg1 mAb that blocked 20% binding of 29 out of 40 PF sera. Furthermore, the immunoreactivity of 45 PF sera against the mature Dsg1 was 3.2 fold stronger than that against the precursor Dsg1 by ELISA. Similar results were observed in anti-Dsg3 Abs in 47 pemphigus vulgaris sera, suggesting that most pemphigus sera target epitopes that are unmasked by proteolytic processing. These findings support the idea that at least some pathogenic pemphigus autoantibodies induce the loss of cell adhesion by directly binding the trans-interaction site of Dsgs. © 2009 The Society for Investigative Dermatology.
Authors & Co-Authors
Saleh, Marwah Adly
Japan, Tokyo
Keio University School of Medicine
Kuroda, Keiko
Unknown Affiliation
Hachiya, Takahisa
Unknown Affiliation
Stanley, John R.
United States, Philadelphia
University of Pennsylvania
Amagai, Masayuki
Japan, Tokyo
Keio University School of Medicine
Ishii, Ken
Japan, Tokyo
Keio University School of Medicine
Statistics
Citations: 52
Authors: 6
Affiliations: 2
Identifiers
Doi:
10.1038/jid.2009.61
ISSN:
15231747
Research Areas
Health System And Policy