Anti-phospholipase A2 receptor antibody in membranous nephropathy; an Indian experience

Introduction: Autoantibodies against phospholipase-A2 Receptor (PLA2R), a normally occurring antigen presented on podocyte membranes, have recently been implicated in the pathology of membranous nephropathy (MN). Objectives: In this observational study, we have evaluated the correlation of patient’s disease activity against serum levels of anti-PLA2R in patients with primary and secondary MN in a North Indian cohort. Patients and Methods: We measured serum anti-PLA2R antibody by ELISA in 63 adult patients with MN. Out of these 63 patients, the majority (58) had primary MN (pMN) and the remaining five had secondary MN (sMN). Results: Around 55.2% had detectable anti-PLA2R autoantibodies (63% in those with new-onset pMN, 67% in patients with relapse and 3% in patients in remission). However, all patients with refractory pMN (n = 4) were anti-PLA2R negative. There was significantly higher anti-PLA2R positivity in active stage of disease in contrast to those in remission (P < 0.001). Autoantibody level was proportional to the disease activity, with a trend towards significance (P = 0.052). Hypoalbuminemia and proteinuria were also significantly worse in the anti-PLA2R positive patients. All patients with sMN tested negative for anti-PLA2R autoantibodies. Conclusion: PLA2R is a major target antigen in Indian population with idiopathic MN. Anti-PLA2R positivity is a specific tool to detect idiopathic MN, and its levels correspond well with other disease activity markers. In addition, anti-PLA2R antibody was negative in refractory pMN, which suggests the existence of additional autoantibodies in this subgroup, with a different target antigen. These autoantibodies may be resistant to the currently recommended immunosuppressants for the disease, thus the refractory nature of the disease.