The role of PLA2R antibody monitoring: what we know and what we do not know

For a long time, kidney biopsy was the only diagnostic means for membranous nephropathy (MN) and proteinuria and serum creatinine were the only markers of disease activity. The discovery of the phospholipase A2 receptor (PLA2R) antibody in 2009 has induced a paradigm shift in both the diagnosis and monitoring of patients. Two serological tests are routinely used: the enzyme-linked immunosorbent assay (ELISA), which is quantitative, and the immunofluorescence assay (IFA), which is more sensitive. In centres where the two assays are available, the recommendation is to use IFA for screening and diagnosis of immunological remission and ELISA for monitoring the effectiveness of therapy. In patients with positive PLA2R antibody serology, normal kidney function and no evidence of 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 and serum creatinine) and PLA2R antibody levels. The 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 kidney allografts. Future studies are needed to develop more subtle immunological tests, including monitoring of antigen-specific memory B cells.

Automated summary

The discovery of PLA2R antibody has transformed the diagnosis and monitoring of membranous nephropathy. The recommended serological tests include ELISA for screening and diagnosis and IFA for monitoring the effectiveness of therapy. A kidney biopsy is not mandatory for patients with positive PLA2R antibody serology, normal kidney function, and no evidence of underlying disease. The risk evaluation of disease progression and effectiveness of therapy should be based on repeated measurements of both traditional biomarkers and PLA2R antibody levels.