#2388 Relevance of anti-PLA2R levels in therapy decision and prediction of therapy outcome in patients with membranous nephropathy
Authors: Kühnl Alexander , Fink Coralien , van de Logt Anne-Els , Dieckmann Kersten , Dähnrich Cornelia , Schlumberger Wolfgang , Wetzels Jack F M 
Published: May 2024

Abstract

Background and Aims
Detection of anti-phospholipase A2 receptor (PLA2R) antibodies in patients with primary membranous nephropathy (MN) supports diagnosis as well as disease monitoring. An individualised therapy approach was introduced for anti-PLA2R positive MN patients at the Radboud University Medical Center. Immunosuppressive treatment (cyclophosphamide combined with steroids) was stopped when anti-PLA2R results by indirect immunofluorescence testing (IIFT) became negative. Here, we evaluated the relevance of anti-PLA2R levels for therapeutic decisions and the outcome of MN, comparing qualitative and quantitative detection methods.

Method
Stored serum samples were retrieved for beginning of treatment (baseline), decision point, and follow-up. Anti-PLA2R levels were determined qualitatively by IIFT as well as quantitatively by enzyme-linked immunosorbent assay (ELISA) and chemiluminescence immunoassay (ChLIA) at baseline as well as after treatment and correlated to immunological remission and persistence.

Results
For an evaluation of the relevance of anti-PLA2R levels at the start of therapy, serum samples of 60 patients were available. Patients sampled at the beginning of the therapy were grouped according to tertiles of anti-PLA2R levels determined by ChLIA (n[lowest tertile] = 20, n[middle tertile] = 20, n[highest tertile] = 20). Lower anti-PLA2R levels were seen in patients with relapsing disease. Higher anti-PLA2R levels were associated with more severe proteinuria. Patients in the lowest tertile of anti-PLA2R were more likely to develop immunological remission after 8 weeks of therapy. In total, 90% vs 75% vs 45% of patients in the tertiles turned anti-PLA2R negative after being treated for 8 weeks. Moreover, in this subgroup of patients who showed immunological remission after 8 weeks of therapy, only 11% of the patients in the lowest tertile needed renewed immunosuppressive therapy, while this percentage increased in the middle and highest tertiles (11% vs 53% vs 33%, p=0.033).
For the assessment of anti-PLA2R levels before and after therapy, samples at baseline and week 8 of treatment were examined. At baseline, 50/50 (100%) tested positive in IIFT and ChLIA as well as 48/50 (94%) in ELISA. After 8 weeks on treatment, immunological remission based on IIFT was found in 37/51 (73%) patients. At this point, the overall agreement compared to IIFT was 92% for ChLIA and 82% for ELISA. Yet the availability of quantitative levels provided further insight into this group of patients in whom treatment was discontinued. With ChLIA, anti-PLA2R titers &gt;5 RU/mL after 8 weeks of therapy were found in 4% of IIFT negative patients with persistent remission, vs 55% of IIFT negative patients with early relapse (p=0.006).

Conclusion
Individualised treatment of MN patients with cyclophosphamide and steroids has been recently introduced. In this respect, the quantitative determination of anti-PLA2R levels adds further value. Of the examined quantitative methods, ChLIA demonstrated the highest agreement with IIFT. Additional studies are needed to evaluate the impact on clinical decision making and outcome.