Comparability of Two Anti-phospholipase A2 Receptor (PLA2R) Enzyme-Linked Immunosorbent Assays (ELISAs) in Patients with Primary Membranous Nephropathy
Bibliographic record
Abstract
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. Funding: Commercial Support - Genentech, Inc., and F. Hoffmann-La Roche Ltd, Private Foundation SupportFig 1. Concordance Between Anti-PLA2R ELISA Titers in MENTOR
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.019 | 0.044 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".