Improvement in CDASI in cutaneous dermatomyositis correlates with change in type I interferons, CD4+ cells, and myeloid dendritic cells

Summary: Dermatomyositis (DM) is an autoimmune disease affecting the skin, skeletal muscle, and/or lungs. While the pathogenesis remains poorly understood, it is thought to be driven largely by type 1 interferons (IFN-b) and involve CD4+ cells, mast cells, and dendritic cells. We aimed to explore expression of these cytokines and cells in relationship to the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) skin activity. We evaluated skin biopsies from 12 patients with moderate-severe cutaneous DM at baseline and after 12 weeks of treatment. Patients were categorized as disease activity responders based on a decrease of 5 points on the CDASI activity. QT-PCR and immunohistochemistry were performed and various cytokines and cell types were analyzed using the Spearman rank correlation and Wilcoxin matched pairs signed rank test. When analyzing all patients, the change in IFN-b mRNA and protein expression correlated with the change in CDASI scores (r¼0.559, p¼0.062; r¼0.629, p<0.05, respectively). In disease responders, there was a significant decrease in IFN-b protein (p<0.01) and mRNA expression (p<0.01) in skin tissue. MxA, induced by type I interferon, showed a significant correlation between the change in mRNA and the change in CDASI scores (r¼0.671, p<0.05). The change in IFN-g protein also correlated with the change in CDASI (r¼0.517, p¼0.088). There was a significant decrease in IFN-g protein expression (p<0.05) in responders. With regards to cells, changes in CD4+ and myeloid dendritic cells, but not mast cells, correlated with changes in the CDASI score (p<0.05). In the disease responders, there was a significant decrease in CD4+ expression (p<0.05). In conclusion, change in CDASI significantly correlates with type I interferons, CD4+, and myeloid dendritic cells.