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Abstract: TH-PO597

Comparability of Two Anti-phospholipase A2 Receptor (PLA2R) Enzyme-Linked Immunosorbent Assays (ELISAs) in Patients with Primary Membranous Nephropathy

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

  • Barbour, Sean, The University of British Columbia, Vancouver, British Columbia, Canada
  • Clarke, Holly, Genentech Inc, South San Francisco, California, United States
  • Berisha, Eriola, F Hoffmann-La Roche AG, Basel, Switzerland
  • Arjomandi, Audrey, Genentech Inc, South San Francisco, California, United States
  • Chen, Debbie, Genentech Inc, South San Francisco, California, United States
  • Riboulet, William, F Hoffmann-La Roche AG, Basel, Switzerland
  • Boston, Heather, F Hoffmann-La Roche AG, Basel, Switzerland
  • Prot, Sylvie, F Hoffmann-La Roche AG, Basel, Switzerland
  • Cattran, Daniel C., Toronto General Research Institute, University of Toronto, Toronto, Ontario, Canada
  • Place, David E., Genentech Inc, South San Francisco, California, United States
Background

In patients with primary membranous nephropathy (pMN), 70-80% have circulating anti-M-type phospholipase A2 receptor (PLA2R) autoantibodies. The EuroImmun (EI) anti-PLA2R (αPLA2R) ELISA is a diagnostic test for pMN used in the ongoing, Phase III MAJESTY clinical trial (NCT04629248), which evaluates the safety and efficacy of obinutuzumab versus tacrolimus in patients with pMN. In the Phase III MEmbranous Nephropathy Trial of Rituximab (MENTOR, NCT01180036), an ELISA developed by Paul Brenchley was used prior to the development of a commercial ELISA. The comparability of the two αPLA2R assays is unknown. Measurement of MENTOR αPLA2R titers using EI-ELISA allows for comparison of outcomes between these B cell depletion clinical trials and informs the MAJESTY protocol design, which uses EI-ELISA.

Methods

Baseline serum samples obtained from MENTOR were analyzed by EI-ELISA. Spearman’s rank correlation was used to assess comparability of the EI-ELISA results. For EI-ELISA, αPLA2R+ was defined as ≥14 RU/mL; αPLA2R+ was defined as >40 U/mL by Brenchley ELISA. The median EI-ELISA αPLA2R titer among αPLA2R+ MENTOR study participants was determined and used for stratification of study participants in MAJESTY.

Results

At baseline, αPLA2R titers in MENTOR were highly concordant (r=0.91, P=1.26x10-49) (Fig 1). At baseline, 93/130 (71.5%) were αPLA2R+ by the EI-ELISA (≥14 RU/mL) and 96/130 (73.8%) were αPLA2R+ (>40 U/mL) by the Brenchley ELISA, with 96.2% agreement. Among patients who were αPLA2R+ as assessed by the EI-ELISA, the median titer was 175 RU/mL (IQR, 58-394).

Conclusion

The EI-ELISA used in the ongoing MAJESTY study is highly concordant with the Brenchley ELISA. To ensure the two arms in MAJESTY have a comparable proportion of participants who are αPLA2R+, the median EI-ELISA αPLA2R+ titer (175 RU/mL) was used for stratification.

Fig 1. Concordance Between Anti-PLA2R ELISA Titers in MENTOR

Funding

  • Commercial Support – Genentech, Inc., and F. Hoffmann-La Roche Ltd