Featured Research

from universities, journals, and other organizations

Common genetic link in fatal autoimmune skin disease discovered

Date:
June 19, 2014
Source:
Perelman School of Medicine at the University of Pennsylvania
Summary:
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. Researchers recently found a shared genetic link in the autoimmune response among PV patients that provides important new clues about how autoantibodies in PV originate.

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 Dermatologyat 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 to PV.

While it's unlikely that the VH1-46 link solves the entire puzzle of PV's origins, it's an important step pointing in the right direction. Payne explains, "We don't think that VH1-46 is everything in PV, because we know that by the time patients show up with full-blown disease, multiple autoantibodies are causing the disease. However, the key is that we find VH1-46 autoantibodies in all of the patients we have studied, which suggests that it may be one of the earliest autoantibodies that appears."

Among the next steps for the research team will be to continue to probe the development of VH1-46 anti-Dsg3 antibodies, specifically whether they cross-react to microbes such as viruses or bacteria. "That could indicate that autoimmunity was mistakenly triggered during the course of an appropriate immune response to infection," says Payne. "Although we don't think this paper is going to immediately affect therapy, we believe that continuing along these lines of study will allow us to better understand how to improve current therapies or develop new strategies to treat disease," she notes. "We're at a really exciting time right now where we have the technologies to be able to address important questions about how PV occurs."

In addition to Payne, other Penn authors on the study include Michael Jeffrey Cho, Arielle R. Nagler, Christoph T. Ellebrecht, Eric M. Mukherjee, Christoph M. Hammers, Eun-Jung Choi, Preety M. Sharma, Hong Li, Sara A. Farber, Courtney B. Rubin, and Bruce S. Sachais. Funding for the study was provided in part by grants from the National Institutes of Health (AR053505, AR057001, P30-AR057217, and HL078726-S1).


Story Source:

The above story is based on materials provided by Perelman School of Medicine at the University of Pennsylvania. Note: Materials may be edited for content and length.


Journal Reference:

  1. Michael Jeffrey Cho, Agnes S.Y. Lo, Xuming Mao, Arielle R. Nagler, Christoph T. Ellebrecht, Eric M. Mukherjee, Christoph M. Hammers, Eun-Jung Choi, Preety M. Sharma, Mohamed Uduman, Hong Li, Ann H. Rux, Sara A. Farber, Courtney B. Rubin, Steven H. Kleinstein, Bruce S. Sachais, Marshall R. Posner, Lisa A. Cavacini, Aimee S. Payne. Shared VH1-46 gene usage by pemphigus vulgaris autoantibodies indicates common humoral immune responses among patients. Nature Communications, 2014; 5 DOI: 10.1038/ncomms5167

Cite This Page:

Perelman School of Medicine at the University of Pennsylvania. "Common genetic link in fatal autoimmune skin disease discovered." ScienceDaily. ScienceDaily, 19 June 2014. <www.sciencedaily.com/releases/2014/06/140619091919.htm>.
Perelman School of Medicine at the University of Pennsylvania. (2014, June 19). Common genetic link in fatal autoimmune skin disease discovered. ScienceDaily. Retrieved September 22, 2014 from www.sciencedaily.com/releases/2014/06/140619091919.htm
Perelman School of Medicine at the University of Pennsylvania. "Common genetic link in fatal autoimmune skin disease discovered." ScienceDaily. www.sciencedaily.com/releases/2014/06/140619091919.htm (accessed September 22, 2014).

Share This



More Health & Medicine News

Monday, September 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Liberia Pleads for Help to Fight Ebola

Liberia Pleads for Help to Fight Ebola

AP (Sep. 22, 2014) Liberia's finance minister is urging the international community to quickly follow through on pledges of cash to battle Ebola. Bodies are piling up in the capital Monrovia as the nation awaits more help. (Sept. 22) Video provided by AP
Powered by NewsLook.com
Ebola Doctor Says Border Controls Critical

Ebola Doctor Says Border Controls Critical

AP (Sep. 22, 2014) A Florida doctor who helped fight the expanding Ebola outbreak in West Africa says the disease can be stopped, but only if nations quickly step up their response and make border control a priority. (Sept. 22) Video provided by AP
Powered by NewsLook.com
Global Ebola Aid Increasing But Critics Say It's Late

Global Ebola Aid Increasing But Critics Say It's Late

Newsy (Sep. 21, 2014) More than 100 tons of medical supplies were sent to West Africa on Saturday, but aid workers say the global response is still sluggish. Video provided by Newsy
Powered by NewsLook.com
Sierra Leone in Lockdown to Control Ebola

Sierra Leone in Lockdown to Control Ebola

AP (Sep. 21, 2014) Sierra Leone residents remained in lockdown on Saturday as part of a massive effort to confine millions of people to their homes in a bid to stem the biggest Ebola outbreak in history. (Sept. 20) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins