The recent buzz in the pemphigus and pemphigoid community stems from the publication of “Population-Specific Association between a Polymorphic Variant in ST18, Encoding a Pro-Apoptotic Molecule, and Pemphigus Vulgaris” in the Journal of Investigative Dermatology (available online, March 2012).
Despite the fact that pemphigus most often affects adults, it seems a large extent may be genetically determined. Indeed, the disease sometimes runs in families. Also, the deleterious antibodies implicated as a major cause of the disease can be found in healthy relatives of patients. And finally, the disease prevalence is highly population-dependent. For example, it is up to 40 times more common in Jewish as compared with non-Jewish populations.
The delineation of the genetic basis of a disease can reveal unknown aspects of its pathogenesis, which in turn is likely to point to novel therapeutic targets. To tackle the genetic basis of pemphigus vulgaris, Dr. Ofer Sarig and Eli Sprecher (Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel) led a collaboration with Ibrahim Saleh (co-Principle Investigator), Detlef Zilliekens, Michael Hertl and Markus M. Nöthen (Germany); Dedee Murrell (Australia), Aviv Barzilai, Henri Trau, Reuven Bergman, Ariel Darvasi, Karl Skorecki, Dan Geiger and Saharon Rosset (Israel).
Over the past two years, they assessed on a global (“genomic”) level the possibility that specific genetic variants may predispose to pemphigus vulgaris. They identified genetic variations in a gene called ST18 associated with the increased incidence of pemphigus vulgaris in Jewish and Egyptian patients. The fact that patients of German origin did not demonstrate the same trend suggests that the ST18 variants shows an increased risk for the disease in a population-specific manner. Carriers of the genetic changes have a 6-fold elevated risk of developing the disease. These genetic variations are associated with an increase in the expression of ST18 in the skin. Since ST18 is known to promote programmed cell death, increased expression of this protein may render the skin tissue more susceptible to the deleterious effects of the pathogenic antibodies.
What started as a posting of the story on Facebook quickly spread to the P/P Email Discussion Group where the talk turned to quicker diagnosis, better treatments, and a cure. Dr. Sprecher said, “The greatest reward for a physician involved in basic research like me is the feedback we get from our patients. This goes much deeper than anything else.” The P/P Community continues to be high-spirited and focused on researching this discovery and hopes more information is available at the IPPF’s Fifteenth Annual Meeting in Boston, May 18-20. 2012.
This step along the path of better understanding disease susceptibility and pathogenesis sheds new light on the genetic association of pemphigus vulgaris. Future work is still needed to more towards better genetic tools that impact disease management and targeted therapies.
But today, we are one step closer than we were yesterday.