314 Mass spectrometry-based plasma proteomics analysis reveals IL-31 inhibition modulates cutaneous and systemic inflammation in prurigo nodularis

Prurigo nodularis (PN) is an intensely pruritic, chronic inflammatory skin disease with diffusely distributed hyperkeratotic nodules featuring cutaneous and systemic inflammation. This study investigated the anti-inflammatory properties of nemolizumab, a humanized anti-IL-31RA antibody, by using unbiased plasma proteomics isobaric Tandem Mass Tags® (TMT®) approach to enrich skin-specific proteins detection. The analysis was performed on samples collected from Phase II nemolizumab. Plasma were PN patients at three timepoints (baseline, week 4, 12), 19 nemolizumab responders (Peak Pruritus NRS reduction 12 > 4) placebo non-responders. super-depleted, digested labelled TMT® subjected LC-MS/MS analysis. To enhance detection proteins, biopsies run in parallel TMTprocalibrator™, novel method amplify skin-related plasma. Differentially expressed protein (DEP) baseline-corrected data pathway employed GO term enrichment. coupled resulted quantification 3,451 unique 392 differentially regulated Nemolizumab treatment. Nemolizumab-treated had dramatic decreases global responses, including decreased STAT3, IL-3, IL-8, IL-15, IL-17 & VEGF signaling, neuronal neuroinflammation, impaired granulocyte activation myeloid cell activation. IL-31 inhibition appears be central regulator decreasing responses PN.