Non-Invasive Assessment of Skin Surface Proteins of Psoriasis Vulgaris Patients in Response to Biological Therapy

Abstract

Measurements of skin surface biomarkers have enormous value for the detailed assessment of skin conditions, both for clinical application and in skin care. The main goals of the current study were to assess whether expression patterns of skin surface hBD-1, hBD-2, IL-1α, CXCL-1, and CXCL-8, examples of proteins known to be involved in psoriasis pathology, are associated with disease severity and whether expression patterns of these proteins on the skin surface can be used to measure pharmacodynamic effects of biological therapy. In this observational study using transdermal analysis patch (TAP), levels of skin surface IL-1α, hBD-1, hBD-2, CXCL-1/2, and CXCL-8 of psoriasis vulgaris (PV) patients over biological therapy were assessed. The Psoriasis Area Severity Index (PASI) and local score for erythema, induration, and desquamation were determined from the exact same skin area as FibroTx TAP measurements. Thirty-seven adult PV patients were included, of which twenty-three were subjected to anti-TNF-α, seven to anti-IL-17A, and seven to anti-IL12/IL-23 therapy. Significantly higher levels of hBD-1, hBD-2, CXCL-1/2, and CXCL-8 were detected on lesional skin compared to the non-lesional skin of the PV patients. In contrast, lower levels of IL-1α were found in lesional skin compared to non-lesional skin. In addition, we observed that the biomarker expression levels correlate with disease severity. Further, we confirmed that changes in the expression levels of skin surface biomarkers during biological therapy correlate with treatment response. Biomarker expression patterns in response to treatment differed somewhat between treatment subtypes. We observed that, in the case of anti-TNF-α therapy, an increase after a steady decrease in the expression levels of CXCL-1/2 and CXCL-8 occurred before the change in clinical scores. Moreover, response kinetics of skin surface proteins differs between the applied therapies—hBD2 expression responds quickly to anti-IL-17A therapy, CXCL-1/2 to anti-IL-12/23, and levels of CXCL-8 are rapidly down-regulated by IL-17A and IL-12/23 therapy. Our findings confirm that the skin surface hBD-2, IL-1α, CXCL-1/2, and CXCL-8 are markers for the psoriasis severity. Further, data obtained during this study give the basis for the conclusion that skin surface proteins CXCL-1/2 and CXCL-8 may have value as therapeutic biomarkers, thus confirming that measuring the ‘molecular root’ of inflammation appears to have value in scoring disease severity on its own.

The Role of Alarmins in the Pathogenesis of Rheumatoid Arthritis, Osteoarthritis, and Psoriasis

“…Conversely, several studies have found that the expression of IL-1α is lower in lesional psoriatic skin than in non-lesional regions, both in adult and pediatric populations [258][259][260]. In addition, a moderate negative correlation between IL-1α and the PASI score has been observed [259]. Moreover, the level of IL-1α in the sera of psoriatic patients has been reported to be lower [261].…”

“…The abovementioned findings led Portugal-Cohen et al to identify IL-1 as a disease biomarker [257]. Conversely, several studies have found that the expression of IL-1α is lower in lesional psoriatic skin than in non-lesional regions, both in adult and pediatric populations [258][259][260]. In addition, a moderate negative correlation between IL-1α and the PASI score has been observed [259].…”

“…As a major inflammatory player, the level of IL-1α in anti-psoriatic treatments has been the subject of research. Treatment with anti-TNF-α, anti-IL-17A, and anti-IL-12/23 agents contributes to an increase in the average level of lesional IL-1α in the skin [259]. Mechanistically, it has been suggested that preformed IL-1α is stored in the deep layers of the epidermis and is used for restoring impaired barrier function.…”