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Penn study reveals a common genetic link in fatal autoimmune skin disease
Date:6/19/2014

PHILADELPHIA Autoimmune disease occurs when the body's own natural defense system rebels against itself. One example is pemphigus vulgaris (PV), a blistering skin disease in which autoantibodies attack desmoglein 3 (Dsg3), the protein that binds together skin cells. Left untreated, PV can be fatal, as skin layers slough off and leave the body vulnerable to dehydration and infection. Researchers from the Perelman School of Medicine at the University of Pennsylvania recently found a shared genetic link in the autoimmune response among PV patients that provides important new clues about how autoantibodies in PV originate. Full results of the new study are available today in Nature Communications.

To better understand the nature of the immune response in PV, the researchers cloned anti-Dsg3 monoclonal autoantibodies (mAbs) from four unrelated PV patients. In characterizing the mAbs, they identified a particular gene, VH1-46, that was used by PV antibodies across all four patients.

"This was a very striking finding, because the common gene suggests common mechanisms for developing the disease," said senior author Aimee Payne, MD, PhD, the Albert M. Kligman Assistant Professor of Dermatology at Penn Medicine. "Most people have common antibody gene responses to infections and vaccinations, so when we first started these studies, we suspected this might be the case for PV, we just didn't know which gene it was going to be."

To investigate further, the team set out to determine the nature and frequency of mutations in the complementarity determining regions (CDRs) of the VH1-46 autoantibodies. CDRs are the parts of the antibody that determine its specific antigen target. The researchers found that with very few CDR mutations, or even none at all, VH1-46 mAbs could bind with the Dsg3 protein. This suggests that the inherent tendency of some VH1-46 antibodies to bind Dsg3 could underlie the cascade of events that ultimately lead t
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Contact: Katie Delach
katie.delach@uphs.upenn.edu
215-349-5964
University of Pennsylvania School of Medicine
Source:Eurekalert

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