Clinical Information

Membranous nephropathy (MN) is a rare disease in which immune complexes deposit at the glomerular basement membrane, causing damage to the filtration barrier, resulting in proteinuria. Recent studies have shown that in approximately 70% of patients with primary MN (pMN), the immune complexes consist of autoantibodies against the podocyte protein M-type phospholipase A2 receptor (PLA2R).(1) There is also evidence that levels of anti-PLA2R autoantibodies correlate well with disease activity and progression.(2) The presence of anti-PLA2R antibodies could also potentially be used to differentiate pMN from other causes of nephrotic syndrome if a biopsy is not possible. Among patients with chronic kidney disease awaiting kidney transplantation, higher levels of anti-PLA2R could predict those more likely to recur after transplantation.(2)

Mayo Clinic Laboratory data suggest that there is a high-concordance between the enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence assay PLA2R results; however, the ELISA assay alone may be preferred for monitoring patients with membranous nephropathy over time for trends in anti-PLA2R antibody levels.

In the remaining 30% of patients with MN who are PLA2R-negative, anti-thrombospondin type-1 domain-containing 7A (THSD7A) was shown to have an approximate 10% prevalence (ie, about 3% of all primary MN patients).(3) Mouse podocytes express THSD7A and introduction of anti-THSD7A autoantibodies induces MN in murine models. Mouse podocytes do not express PLA2R so exogenous administration of anti-PLA2R does not recapitulate MN in mice.(4) Additionally, THSD7A has been described as a potential tumor antigen and, thus, it has been suggested that THSD7A-positive patients merit a thorough cancer screening.(5)