Myeloid-related proteins-and -14 are expressed but dispensable in the pathogenesis of experimental epidermolysis bullosa acquisita and bullous pemphigoid

Background: Myeloid-related protein-(MRP-8) and its heterodimeric partner, MRP-14 belong to the group of danger-associated molecular patterns (DAMPs) and are associated with numerous chronic human disorders. However, their functional role in autoimmunity remains largely unclear. Objective: Here, we examined the involvement of MRP-8/-14 in two difficult-to-treat autoimmune blistering diseases, epidermolysis bullosa acquisita (EBA) and bullous pemphigoid (BP). Methods: MRP-8/-14 concentrations in the sera of EBA and BP patients were quantified by ELISA. Experimental EBA and BP in mice were induced by transfer of antibodies directed against type VII or XVII collagen, respectively. Expression of MRP-8/-14 was analyzed in skin samples of these experimental mouse models. The functional role of MRP-8/-14 proteins was evaluated by the induction of experimental EBA and BP in MRP-14-deficient mice. Results: We found serum levels of MRP-8/-14 to be elevated in both, EBA and BP patients. Furthermore, in the lesional skin of mice with experimental diseases expression of MRP-8/-14 was increased as compared to healthy controls. However, MRP-14-deficient mice were fully susceptible to experimental disease with a phenotype comparable to that of wild type controls. Conclusion: Although MRP-8/-14 expression is highly increased in experimental as well as human disease, these proteins do not contribute to the pathogenesis in the effector phase of EBA and BP.