NEW YORK (GenomeWeb) – In a study appearing online today in Science Translational Medicine, researchers from Germany, the UK, and Italy described skin gene expression shifts that correspond to the presence of psoriasis or eczema — conditions that can be tricky to tell apart.
Along with their potential for diagnosing the skin problems, these disease-specific expression changes may ultimately point to new avenues for treating psoriasis and eczema, the study's senior author Kilian Eyerich, a dermatology and allergy researcher at the Technical University of Munich, told GenomeWeb Daily News in an email message.
Starting with a between-individual comparison of array-based skin gene expression patterns in two dozen individuals affected by both psoriasis and eczema, Eyerich and his colleagues saw some immune system components and other gene players that spring into action in both inflammatory skin conditions.
But the researchers also narrowed in on genes showing expression changes in psoriasis or eczema alone, along with signatures associated with specific forms of eczema. And in follow-up tests on dozens more individuals with just one of the skin conditions, they found that expression levels for just two of the genes could correctly classify psoriasis and eczema patients, even uncovering an apparent misdiagnosis in one case.
While some forms of psoriasis and eczema are straightforward to identify based on their clinical presentation alone, Eyerich and his co-authors noted, other cases are more difficult to diagnose. Moreover, they explained, effective treatment may depend not only on an accurate diagnosis, but also an understanding of the pathways that are altered in each of the diseases.
In an effort to overcome experimental noise associated with inter-individual differences in inflammatory skin disease response, the researchers decided to begin by looking for shared and distinct disease contributors in individuals affected by both conditions.
"This study rules out any inter-individual differences by comparing psoriasis and eczema lesions within the same patients," Eyerich and co-authors noted. "Thus … observed regulated genes are not driven by the genetic background but depend exclusively on the local stimulus that creates a microenvironment, leading to the clinical phenotype of psoriasis or eczema, respectively."
Using Agilent SurePrint G3 Human GE 8X60K BeadChip arrays, they profiled gene expression in skin punch biopsy samples from 24 psoriasis patients who also had atopic, non-atopic, or contact eczema.
By comparing affected and unaffected skin samples in each individual — and looking at gene expression patterns across the participant group — the team saw 45 genes with similar jumps or declines in skin affected by either psoriasis or eczema. Another 39 genes had either increased or diminished expression in the eczema skin samples, while 101 genes showed altered expression in skin taken from psoriatic plaques.
A closer look at the nature of these genes suggested that both of the inflammatory skin conditions involve changes in activity by genes from epidermal, metabolic pathways, and immune pathways. For example, some epidermal remodeling and adaptive immune responses appeared to be active in both conditions, as was the innate immune system.
But the researchers found that psoriatic skin was more prone to involvement by wound healing branches of the immune system. Those samples showed a jump in activity by genes coding for cytokines from the interleukin-10 family, for instance, and components of a T-helper 17 pathway.
Although some cytokines were induced in eczema as well, the precise set was somewhat different, the researchers reported, suggesting eczema spurs a more acute immune reaction. That immune response, coupled with skin dryness and a breakdown in the skin's barrier, resembles responses that have been detected in microbe-colonized skin, Eyerich noted.
There were differences detected in the metabolic and epidermal pathways predominantly affected in the skin conditions, too. In particular, the analysis pointed to metabolic shifts in glucose, lipid, and amino acid pathways in psoriasis samples, which also tended towards expression of keratinization genes and genes involved in early epidermal development and differentiation.
The researchers found that genes contributing to epidermal barrier function were more often affected in eczema tissues, though tissue from specific eczema sub-types displayed a jump in genes associated with early and late epidermal differentiation.
In those with acute contact dermatitis, on the other hand, they saw a decline in late differentiation markers, but a boost in activity by genes involved in apoptosis, adhesion, and inflammasome activity.
"It became obvious that eczema is a heterogeneous group of diagnoses," Eyerich said.
"We saw especially differences regarding self-limited forms such as contact dermatitis and chronic forms such as atopic eczema," he explained, noting that the trigger associated with contact dermatitis could contribute to some of the variability in immune response identified in the eczema samples.
When they attempted to classify samples from 19 patients with either psoriasis or eczema alone, using expression data for 15 genes, the researchers found two genes with expression patterns most closely tied to either psoriasis or eczema.
In yet another set of 16 psoriasis and 18 eczema patients, they demonstrated that expression profiles of those two genes — CCL27 and NOS2 — correctly classified all of the samples, re-assigning one case diagnosed as psoriasis to eczema.
So far, the two-gene classifier appears to perform well in expanded test cohorts, according to Eyerich, who noted that the next step will be to assess the signature in blinded studies done with large sample sizes.
In parallel, he and his team plan to pursue immunohistochemistry- and immunofluorescence-based methods for classifying psoriasis and eczema cases. They are also interested in learning more about potential treatment targets identified in the current study.
"[O]ur vision is that this study paves the way towards personalized medicine in inflammatory skin diseases," Eyerich said. "By linking the molecular signature of the disease with subtypes of psoriasis or eczema — and especially with the clinical response to specific therapies — we intend to create a database that should enable us to predict the best possible therapy for each individual patient based on his or her molecular signature."