403 Increased Expression of Oncostatin M Receptor β in Chronic Pruritic Diseases

Abstract

Chronic Pruritus (CP), a primary symptom in dermatological conditions, is often intractable and strongly impacts patient quality of life. Expression of CP-related biomarkers, Oncostatin M receptor β (OSMRβ) and Interleukin-31 (IL-31), were assessed in these CP-presenting diseases: Chronic Idiopathic Pruritus (CIP), Chronic Idiopathic Urticaria (CIU), Lichen Planus (LP), and Lichen Simplex Chronicus (LSC) and correlated with clinical features. mRNA and protein expression from archived skin samples from disease and non-pruritic control patients were analyzed by RNAscope and Immunohistochemistry (IHC) methods for IL-31 and OSMRβ expression levels. Level of pruritus at time of biopsy was determined by medical chart analysis. Pruritus was reported using a verbal rating scale. Mean OSMRβ mRNA (RNAScope) levels of all disease samples tested (n=10-12 per cohort) were approximately 2-3-fold higher (p≤0.02) in epidermis, compared to normal controls (n=8). Mean OSMRβ protein levels (IHC) were approximately 2-3-fold higher (p<0.01) in epidermis of CIU and LP samples, and mean IL-31 protein levels were approximately 3-fold higher (p=0.02) in epidermis of LP samples, as compared to normal controls (n=10 per cohort). Higher IL-31 mRNA levels correlated with itch severity in LP. Higher OSMRβ mRNA levels correlated with itch severity in LP, LSC and CIU. These results show OSMRβ mRNA is upregulated in biopsies from CIP, CIU, LP and LSC patient skin and at the protein level for CIU and LP, advancing our understanding of the molecules potentially implicated in pruritic disease pathologies. Targeting IL-31 and OSMRβ axes with pharmacological intervention in CP-presenting diseases may provide therapeutic benefits to patients. KPL-716, an antibody targeting OSMRβ, is in Phase 2 clinical trial for treatment of pruritus in CIP, CIU, LP and LSC (NCT03858634).