Rockfeller University logoJames G. Krueger, head of the Laboratory for Investigative Dermatology at Rockefeller University along with colleagues recently revealed the molecular details that differentiate two of the most common forms of inflammatory skin disease, atopic eczema and psoriasis. Supposedly, this drilling and the ability to distinguish between the disorders’ genetic and immunological signatures could pave the way for therapies that are more narrowly targeted.

A common belief is that dermatologists perform one of the two activities when faced with a skin disease. If it’s too dry, they try to wet it and if it’s too wet, they try to dry it. Though there appears to be some wisdom in this general approach, Krueger suggests that it shows a lack of sophisticated treatments for a number of skin conditions. With the help of experiments, the researchers were able to identify the genomic differences of common skin diseases. This finding should help the millions of people afflicted worldwide.

Led by Visiting Fellow Emma Guttman and Research Associate Mayte Suarez-Farinas, the experts utilized wide genetic tests to gain more information about the gene expression patterns found in skin samples of both diseases and normal skin. They also claim to have analyzed the activity initiated by each of the diseases in the immune system. Defining the unique signaling molecules named cytokines. These are supposedly generated by T cells produce in the face of each threat to direct the immune response.

The scientists were able to confirm immunological distinctions that were apparently recognized earlier. However they claim to have discovered even more noticeable differences in the expression of genes that controlled the differentiation of skin cells. This they suggest should help establish a novel paradigm for accurately classifying the diseases.

Causing chronic inflammation, atopic eczema is known to irritate patches of skin, often leading to ‘wet’ lesions. Psoriasis is also considered to be chronic and generally generates red and scaly ‘dry’ rashes. Except for systemic immune suppression, these diseases apparently do not respond to the same treatments. If prolonged and not approved by the FDA, this may increase their danger. Guttman reveals that other prevalent techniques seem to be inadequate.

The researchers bring to light that previously, genetic testing of eczema and psoriasis did not seem to have used enough samples to generate the statistical power. This was essential to definitively establish how each disease could differ from normal skin. Up until now, scientists claim to have centered their attention in particular on a defect in one gene linked with some cases of eczema namely filaggrin.

According to the investigators, filaggrin, however is only one of 150 to 200 genes that appear to include the epidermal differentiation complex. As per the new research, the expression of many of these genes seems to be suppressed in eczema, particularly in those genes responsible for producing the hard, insoluble envelope surrounding skin cells. Loricrin, one specific gene was found to have been expressed at only two percent of its level in normal skin. In contrast, psoriasis was generally found to augment the expression of many of these genes.

Until this analysis, animal models seem to have directed the development of novel therapies for human skin disorders. But, it appears to have been difficult to ascertain if a model stimulated psoriasis, atopic eczema or some other inflammatory disorder. Besides, treatments that calimed to have potential in animals were not found to have largely translated efficiently to humans. Researchers belive this new investigation to be a ‘game-changer’

“What we’ve got is a means to critically evaluate the models of these diseases in animals in a way that wasn’t possible before,” mentioned Krueger, who is also director of Rockefeller’s Milstein Medical Research Program.

Scientists associated with the finding hope that since they could detail the gene expression profile of each disease besides also zeroing in on a critical difference in how they operate at the molecular level, they should come up new drugs and treatments.

“Atopic eczema is widely prevalent and understudied. We’ve begun a process that may take years to come to fruition, but this is where you start to look for better treatment targets,” Krueger says. “You find the fundamental defects, and that’s what we’ve done.”

New possibilities suggesting narrow-acting immuno-suppression drugs or treatments like for the barrier around skin cells could strike individual vulnerabilities in the diseases without really harming the patients.

This finding was published in The Journal of Allergy and Clinical Immunology.