Anti-Phospholipase A2 Receptor Antibody and Recurrent Membranous Nephropathy.

Introduction: Recurrence of Membranous Nephropathy (MN) is associated with reduced kidney graft survival with no predictive factors to manage recurrence. Anti-PLA2R are described in 70% of cases of idiopathic MN, linked with HLA DQ2 status, disease activity and poor clinical outcome. In MN cases who received a renal transplant, we explored the relationship of anti-PLA2R status at and post transplantation, in conjunction with DQ matching and development of recurrent MN. Methods. In a single transplant centre retrospective study using serum stored in the Transplant Biobank, we measured anti-PLA2R by ELISA in 26 adult patients with biopsy proven MN transplanted between 1988-2013. Patients included 21 IMN and 5 secondary MN with anti-PLA2R assayed during primary disease, a few months prior to transplantation and prospectively post transplantation. HLA-DQ typing of donor/recipient was performed using LABType®SSO high definition kits (One Lambda Inc). Post transplant biopsies were performed for clinical reasons e.g. declining renal function and proteinuria. Results: Fifteen of 21 IMN patients (71.4%) and none of five secondary MN patients were positive for anti-PLA2R associated with their primary disease. Of the 15 seropositive IMN patients, 11/15 (73.3%) were DQ2. Immediately prior to transplantation, 9/15 (60%) were still seropositive for anti-PLA2R and 6/9 (66.6%) were DQ2. Post transplantation, in the face of immunosuppression, 5/9 (55.6%) had anti-PLA2R (detected at 1, 4, 26, 40 and 48 months post-transplant and all 5 cases were DQ2. All of these 5 cases had been biopsied for clinical management and 3/5 (60%) had proven recurrent MN (2/5 other pathologies). All 5 cases seropositive for anti-PLA2R post-transplant had received a donor kidney matched at DQ2 Conclusions: This pilot study identifies the presence of anti-PLA2R antibodies post transplantation in association with a DQ matched kidney where 60% of cases biopsied have biopsy proven recurrent MN. This warrants the analysis of a large series of transplanted IMN cases to test the hypotheses a) that presence of anti-PLA2R antibodies post transplantation are pathogenic for the allograft, b) matching at DQ2 may perpetuate anti-PLA2R antibodies in recipient patients with IMN as their native disease.