- Design
- Diagnostic assay development and validation study
- Population
- 20 NELL1+ and 20 PLA2R+ biopsy-proven MN patients; independent cohort of 63 MN cases and 20 controls
- Primary outcome
- Sensitivity and specificity of anti-NELL1 LIPS assay
- Effect
- Sensitivity 90%, specificity 100%; titres tracked proteinuria in 3 patients
NELL1 is one of the recognised target antigens in membranous nephropathy besides PLA2R, but NELL1 disease is currently diagnosed mainly by kidney biopsy staining or mass spectrometry. This study (published June 2026) developed a luciferase immunoprecipitation (LIPS) assay for circulating anti-NELL1 antibodies.
In 20 biopsy-proven NELL1-positive and 20 PLA2R-positive, NELL1-negative patients, the assay had 90% sensitivity and 100% specificity, with better specificity than ELISA. In an independent cohort of 63 membranous nephropathy cases, six were NELL1-positive. In three seropositive patients followed over time, antibody levels tracked proteinuria.
NELL1 membranous nephropathy has been linked with malignancy and certain drugs in some series, so identifying it matters. The assay is research-only and needs larger validation, but it points towards NELL1 being managed like PLA2R disease, with serology for diagnosis and monitoring.
- In membranous nephropathy negative for anti-PLA2R, ask the pathologist about NELL1 staining on the biopsy.
- NELL1-positive disease should prompt review for associated malignancy and causative drugs.
- Serological NELL1 testing is not yet commercially available.
- Monitoring antibody titres may in future guide treatment, as with PLA2R.
Why it matters
It could bring NELL1 membranous nephropathy into the serology-guided care now standard for PLA2R disease.
Don't overread it
This is an early assay validation in small cohorts; it is not a clinical test yet.
The statistics, in plain English
Sensitivity and specificity were estimated in only 40 validation samples, so the true values could be considerably lower. The monitoring finding rests on three patients.
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