Questions and Caveats in Antigen-Defined Membranous Nephropathy

Abstract Remarkable progress has been made in the discovery of autoantigens in membranous nephropathy. With increasing testing for membranous antigens in daily practice, it is important to consider the varying strength of association between certain antigens and underlying conditions. This review explores questions and caveats which arise when assessing results of membranous antigen testing. Specifically, we will discuss: 1) discrepancy between tissue antigen and clinical scenario, focusing on PLA2R; 2) one antigen ≠ one clinical condition, i.e., the heterogeneity of membranous antigens seen in one clinical condition (such as in sarcoidosis), and conversely, heterogeneity of conditions associated with one antigen (such as for neural epidermal growth factor-like 1 (NELL1)); 3) rare presence of multiple membranous associated antigens in tissue or blood (such as with anti-protocadherin 7); and 4) lupus membranous nephritis related antigens and their influence on diagnosis or treatment.