Published October 18, 2013
University at Buffalo researchers have identified a protective mechanism for a rare autoimmune skin disease in healthy, though genetically susceptible, individuals.
“We believe this is the first time such a protection signature has been identified for any autoimmune condition,” says Animesh A. Sinha, MD, PhD, Rita M. and Ralph T. Behling Professor and Chair of the Department of Dermatology.
“Our findings introduce a potentially paradigm-shifting concept of how autoimmunity in general might be kept at bay in genetically susceptible individuals,” adds Sinha, the corresponding author on the study.
The finding occurred as the research team worked to develop the first genome-wide transcriptional analysis of Pemphigus vulgaris (PV), a blistering skin condition that is life-threatening if untreated.
The researchers conducted a microarray screening of more than 54,000 genes in the blood of 31 participants: 13 with active PV, eight in remission and 10 healthy controls.
Some of the control participants carried genetic markers that Sinha had previously identified to be associated with the development of PV, yet these individuals did not develop autoimmunity.
In the recent study, these genetically at-risk individuals were found to “have down-regulated the expression of a broader set of additional genes in their blood that were up-regulated in patients with PV,” Sinha explains.
“This suggests a ‘protection signature’ in healthy individuals carrying genetic risk elements,” he says.
“Eventually, we might be able to leverage information contained within the ‘natural response’ of the immune system to develop entirely new strategies to block disease,” says Sinha, whose lab is in the UB Clinical and Translational Science Institute.
“With this knowledge, it may be possible to identify genes and immune pathways that can be manipulated in patients and at-risk individuals to prevent — or even reverse — the development of autoimmunity,” he concludes.
The research also may lead to more individually tailored treatments, he adds.
The paper, “Genome-Wide Expression Analysis Suggests Unique Disease-Promoting and Disease-Preventing Signatures in Pemphigus Vulgaris,” has been published in Genes and Immunity by the Nature Publishing Group.
Other contributors, both with the Department of Dermatology, are Rama Dey-Rao, PhD, post-doctoral associate, and Kristina Seiffert-Sinha, MD, research assistant professor.
Initiated at Weill Medical College of Cornell University/New York Hospital, the research was funded by the Colleck Research Fund, UB’s Behling Dermatology Fund and UB.