Abstract
Because development of reliable biomarkers in psoriasis and atopic dermatitis has lagged behind therapeutic progress, we created a blood-based test to fill the void in objective methods available for dermatological assessments. Our novel interleukin-19 (IL-19) immunoassay was initially tested to determine concentrations of IL-19 serum levels, then correlated with the psoriasis activity and severity index (PASI) in psoriasis, and the eczema area and severity index (EASI) in atopic dermatitis. Not only was IL-19 increased in psoriasis and correlated to PASI, but ixekizumab administration led to rapid, sustained IL-19 decreases to normal levels, with decreases at 2-weeks correlating with PASI improvement at 16-weeks. IL-19 increased upon ixekizumab withdraw, prior to relapse, and decreased following re-treatment. In baricitinib- and etanercept-treated psoriasis patients, IL-19 decreases also correlated with improvement. Many patients with limited skin disease, including genital psoriasis and psoriatic arthritis patients, also had increased IL-19, which was reduced to normal levels upon ixekizumab treatment, correlating with PASI improvement. We also measured IL-19 in baricitinib-treated atopic dermatitis patients. In atopic dermatitis, IL-19 was significantly elevated, correlated with EASI scores, and decreased with skin improvement. Therefore, measurement of serum IL-19 provides clinicians with an objective disease-activity assessment tool for psoriasis and atopic dermatitis patients.
Highlights
Psoriasis is a chronic inflammatory skin disease mediated by a dysregulated immune system characterized by red, thickened skin and an angiogenic tissue response to stress, injury, and infection[1,2]
To determine if circulating interleukin 19 (IL-19) was elevated in patients with psoriasis and/or correlated with psoriasis activity and severity index (PASI) scores, serum IL-19 was first measured in 36 healthy subjects (Fig. 1a)
Serum IL-19 concentrations measured in baseline samples from patients with psoriasis enrolled in a phase 2 ixekizumab psoriasis study were markedly elevated
Summary
Psoriasis is a chronic inflammatory skin disease mediated by a dysregulated immune system characterized by red, thickened skin and an angiogenic tissue response to stress, injury, and infection[1,2]. Plaque type psoriasis is typically measured using the naked eye for calculating the overall body surface area (BSA) involvement alone, or combined with the degree of erythema, thickness, and scaling of lesions (psoriasis area and severity index, PASI), or using the static Physician’s Global Assessment (sPGA) These visual methods to assess disease activity may not be linear with limited skin involvement. While psoriasis patients are typically classified as having moderate-to-severe disease when BSA is greater than 10% and PASI is greater than 10, the lack of a reliable test method for inflammatory burden has precluded addressing whether patients with so-called mild skin involvement have significantly less overall disease activity[3] These translational gaps in contemporary medical practice prompted us to search for a novel, objective biomarker assay for monitoring disease activity across a spectrum of skin involvement using sera from psoriasis www.nature.com/scientificreports/. Our findings indicate that a serum IL-19 assay for disease activity could provide to clinicians managing psoriasis patients an important tool to complement the therapeutic advances being made in treating this chronic, immune-mediated, skin disease[14]
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