Pre‐transplant phospholipase A2 receptor autoantibody concentration is associated with clinically significant recurrence of membranous nephropathy post‐kidney transplantation

Abstract

Previous studies that have assessed the association of pre-transplant antiphospholipase A2 receptor autoantibody (PLA2R-Ab) concentration with a recurrence of membranous nephropathy (rMN) post-kidney transplant have yielded variable results. We tested 16 consecutive transplant patients with a history of iMN for pre-transplant PLA2R-Ab. Enzyme-linked immunosorbent assay titers (Euroimmun, NJ, USA) >14 RU/mL were considered positive. A receiver operating characteristic (ROC) analysis was performed after combining data from Quintana et al. (n = 21; Transplantation February 2015) to determine a PLA2R-Ab concentration which could predict rMN. Six of 16 (37%) patients had biopsy-proven rMN at a median of 3.2 yr post-transplant. Of these, five of six (83%) had a positive PLA2R-Ab pre-transplant with a median of 82 RU/mL (range = 31-1500). The only patient who had rMN with negative PLA2R-Ab was later diagnosed with B-cell lymphoma. One hundred percent (n = 10) of patients with no evidence of rMN (median follow-up = five yr) had negative pre-transplant PLA2R-Ab. In a combined ROC analysis (n = 37), a pre-transplant PLA2R-Ab > 29 RU/mL predicted rMN with a sensitivity of 85% and a specificity of 92%. Pre-transplant PLA2R-Ab could be a useful tool for the prediction of rMN. Patients with rMN in the absence of PLA2R-Ab should be screened for occult malignancy and/or alternate antigens.

The Most N-Terminal Region of THSD7A Is the Predominant Target for Autoimmunity in THSD7A-Associated Membranous Nephropathy

“…4 -6 Therefore, measurement of anti-PLA2R1 antibodies is useful for diagnosis, individual risk assessment, and monitoring of treatment in patients with MN, including the time after transplantation. [7][8][9][10] The prevalence of THSD7A-associated MN is significantly lower compared with that of PLA2R1-associated MN, and the clinical usefulness of anti-THSD7A autoantibody measurement is currently under investigation. 11 Noteworthy, 20% of white patients with THSD7A-associated MN have concurrent malignancies, suggesting that intensive screening for malignancies is advised in these patients.…”

Antibodies against ARHGDIB are associated with long-term kidney graft loss

“…15,22 Antibodies against PLA2R, LPLUNC, APMAP, and PRKCZ were described previously in small case-series and have not been further evaluated. [23][24][25] During the development of our non-HLA antibody assay we found that MFI results on a specific bead was comparable between singleplex and multiplex measurement, indicating no occurrence of compromise by multiplex analysis. In general, non-HLA antibodies frequently occur within the healthy population and for many autoantibodies a serum is considered positive when exceeding a cut-off yielding a limited (<5%) frequency of positive results within the healthy population.…”

Membranous nephropathy in the kidney allograft

“…In one study of seven patients with rMN, six had at‐risk HLA‐DQ alleles, the presence of which was significantly associated with pretransplant PLA2R antibody levels . Another study found that four of five patients with rMN had at‐risk HLA‐DQ alleles, as compared to five of nine without recurrence, but this was nonsignificant ( P =.6) …”

“…Likewise, Gupta et al . studied 16 patients with pMN consecutively transplanted at the University of Virginia.…”

“…56 Another study found that four of five patients with rMN had at-risk HLA-DQ alleles, as compared to five of nine without recurrence, but this was nonsignificant (P=.6). 57 Possibly owing to this genetic susceptibility to pMN, a higher rate of recurrence was noted with living related donors compared to unrelated donors in a small single-center study. 58…”