The role of PLA2R antibody monitoring: what we know and what we don't know.

For a long time, kidney biopsy was the only diagnostic mean for membranous nephropathy (MN), and proteinuria and serum creatinine the only markers of disease activity. The discovery of PLA2R antibody in 2009 has induced a paradigm shift in both the diagnostic and monitoring of patients. Two serological tests are routinely used: the ELISA which is quantitative and the immunofluorescence assay (IFA) which is more sensitive. In centers where the 2 assays are available, the recommendation is to use IFA for screening and diagnostic of immunological remission, and ELISA for monitoring effectiveness of therapy. In patients with positive PLA2R antibody serology, normal kidney function and no evidence for an underlying disease, a kidney biopsy is not mandatory given the almost 100% specificity of the assays. Because MN has different phases, one cannot base a clinical or therapeutic decision on a single measurement of PLA2R antibody at baseline. Risk evaluation of disease progression is a dynamic process that should be performed repeatedly to capture the trajectory of the disease based on both the traditional biomarkers (proteinuria, serum creatinine) and PLA2R antibody levels. Effectiveness of therapy is also evaluated on the PLA2R antibody trajectory, particularly during the first 6 months. Finally, PLA2R antibody monitoring has transformed the management of patients with a kidney allograft. Future studies are needed to develop more subtle immunological tests, including monitoring of antigen-specific memory B cells.