IL-31 protein expression in lesional skin correlates with itch in Dermatomyositis

Summary: Background/Purpose: Dermatomyositis (DM) is an inflammatory myopathy where itch is a major contributor to impaired quality of life. Previously, we have shown that a cytokine responsible for itch in other diseases, interleukin (IL)-31, is elevated in lesional skin of DM patients. We aim to i) demonstrate the correlation between IL-31 protein expression in lesional skin and clinical assessment tools of itch severity and disease activity; ii) investigate the relationship between IL-31 protein expression in DM responders vs. non-responders in terms of itch and disease activity; iii) identify the cellular source of IL-31 in DM. Methods: IL-31 protein expression in skin was quantified using immunohistochemistry (IHC) analysis of lesional skin samples of 12 DM patients at two separate time points. The visual analog scale (VAS), and SKINDEX-29 Symptoms Score clinical assessment tools, and Cutaneous Disease and Activity Severity Index (CDASI) were used to evaluate itch and disease activity. IHC co-localization of CD4, IL-31, and either IFN-gamma (Th1) or IL-4 (Th2) was performed on baseline lesional skin samples from 5 DM patients to identify the cellular source of IL-31. Results: IL-31 expression with respect to mean cell intensity in lesional skin was highly correlated with SKINDEX-29 Symptoms Score, SKINDEX-29 question 10, and VAS itch score (r=0.85, p<0.001; r=0.77, p<0.01; r=0.68, p<0.05 respectively). IL-31 expression with respect to area stained was highly correlated with CDASI (r=0.78, p<0.01). These correlations were maintained at visit 6 (r=0.65, p<0.05; r=0.64, p<0.05; r=0.60, p<0.05; r=0.74, p<0.01). Itch responders had a greater reduction of IL-31 relative to non-responders with respect to mean cell intensity (p<0.05). Disease responders had a greater reduction in IL-31 staining area relative to non-responders (p<0.05). IHC co-staining of IL-31 with Th1 and Th2 markers demonstrated strong co-localization of IL-31 with Th1 T-cells and relatively little Th2 production of IL-31. Conclusion: IL-31 cell intensity in lesional skin correlates strongly with itch severity while IL-31 staining area is highly correlated with disease activity. The source of IL-31 in DM is likely to be from Th1 cells rather than Th2 cells.