Background and aims Autoantibodies to M-type phospholipase A2 receptor (PLA2R) are specific markers of idiopathic membranous nephropathy (MN). It has also been suggested that anti-PLA2R antibody is associated with disease activity and prognosis but more solid evidence is needed. We aimed to establish quantitative measurement of anti-PLA2R antibodies and further investigate its clinical usefulness.

Methods Using stable cell line expressing PLA2R, we developed a quantitative cell-based enzyme-linked immunosorbent assay (ELISA) and Western blot (WB) for anti-PLA2R antibodies. The usefulness of these tests and the commercial solid phase ELISA were retrospectively studied in sera from 23 patients with biopsy-proven primary MN, and 16 patients with lupus MN. Repeated sera were also available in 9 patients with primary MN.

Results Anti-PLA2R antibodies were detected in 12, 6, and 12 out of 23 patients with primary MN by the WB, the cell-based ELISA, and the commercial solid phase ELISA, respectively. Conversely, all of the samples from the lupus MN patients were negative. The levels of proteinuria were moderately correlated with titers of anti-PLA2R antibodies by the 3 methods (r=0.39 to 0.47). Anti-PLA2R antibodies were significantly associated with physicians’ decision on immunosuppressive therapy without prior knowledge of anti-PLA2R antibody positivity (p<0.01). In all of the 6 patients who were treated with immunosuppressive therapy, titers of anti-PLA2R antibodies significantly declined by commercial solid-phase ELISA (p=0.03).

Conclusions This study showed that anti-PLA2R antibody is clinically useful as diagnostic and surrogate biomarkers in primary MN. In addition, the 3 methods are all reliable measurement methods for anti-PLA2R antibodies but demonstrated different performance.