Epitope Characterization and Design of Epitope Binding Proteins for Idiopathic Membranous Nephropathy: New Tools for Autoimmune Kidney Disease Therapy

Abstract

In autoimmune diseases antibodies incorrectly attack normal healthy cells, which can promote degradation of tissues and can lead to long‐term disease and death. Modern clinical therapies treating autoimmune disease include the use of immunosuppressive medicines. Although this therapy has shown success in slowing down the progression of autoimmune disorders, this treatment diminishes the patient's entire immune system's ability to fight off normal pathogens. This highlights the need for more specific treatment options for autoimmune disease that do not weaken the patient's entire immune system. Primary membranous nephropathy (PMN) is a kidney specific autoimmune disease currently being treated with immunosuppressive medicines. In patients with PMN, seventy percent of individuals produce autoantibodies that target the phospholipase A2 receptor (PLA2R). The goal of this research is to design PLA2R specific binding proteins (epitope caps) that will prevent the PLA2R autoantibodies from binding to the C‐type lectin domain number seven (CTLD7) on this antigen. Using Epitopia and EPCES, three possible epitope sites were identified and characterized. Binding strength of the binding proteins to the CTLD7 was measured through Rosetta Online Server that Includes Everyone. In silico mutations were made to the Monobody template 5FXB. Currently, we have produced three epitope caps (5FXB‐001‐LVG, 5FXB‐002‐LVG, 5FXB‐003‐LVG) with binding scores that are below out targeted binding score of −5.0 Rosetta energy units (REU). Currently protein expression and purification is underway to permit further evaluation of the epitope caps using ELISA assays to determine experimental binding proficiency. Furthermore, this research could provide patients with more specific methods of treatment for autoimmune disease than the contemporary treatment options such as, immunosuppressive therapies. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.