The significance of anti-PLA2R antibody in the diagnosis and treatment of primary membranous nephropathy

Primary membranous nephropathy (PMN) is a glomerulus-specific autoimmune disorder mainly caused by challenge of autoantibodies against the recently discovered antigens located on podocytes, such as the M-type phospholipase A2 receptor (PLA2R), the thrombospondin type-1 domain-containing 7A (THSD7A) and exostosin 1/2 (EXT1/2). At present, the detection of anti-THSD7A and anti-EXT1/2 in PMN are still in an emerging stage, but the quantitative detection of anti-M-type phospholipase A2 receptor antibody (anti-PLA2R) is commercially available. The identification of anti-PLA2R provides important information for clinical and immunopathological differential diagnosis of primary and secondary membranous nephropathy.Anti-PLA2R levels are closely related to disease activity. Low anti-PLA2R baseline levels or decreased anti-PLA2R titers strongly predict spontaneous remission of PMN and are therefore more likely to be treated conservatively. In contrast, high anti-PLA2R baseline levels or elevated anti-PLA2R titers are associated with continuous presence of proteinuria and progressive decline in renal function, and thus tends to initiate immunosuppressive therapy. Serum anti-PLA2R levels can predict therapeutic effect, and the anti-PLA2R levels after treatment can predict long-term prognosis of PMN. Anti-PLA2R may reappear or increase before the disease relapse, and when anti-PLA2R keeps positive or reappears after kidney transplantation, it suggests relapse of PMN. We propose to use this serological-based individualized test in the diagnosis and assessment of PMN to supplement and improve the previous assessment method and increase prognosis of PMN.