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. 2025 Sep;108(3):427-432.
doi: 10.1016/j.kint.2025.05.025. Epub 2025 Jun 18.

Detection and characterization of NELL1 autoantibodies in NELL1 positive membranous nephropathy

Tiffany N Caza  1 , Brock A Arivett  2 , Samar I Hassen  3 , Laith F Al-Rabadi  4 , Suguru Takayama  4 , Abdelrahman Ibrahim  4 , Christopher P Larsen  3 , Dorin Bogdan Borza  5
Affiliations

Detection and characterization of NELL1 autoantibodies in NELL1 positive membranous nephropathy

Tiffany N Caza et al. Kidney Int. 2025 Sep.

Abstract

Introduction: Discovery of novel autoantigens in membranous nephropathy provides promise for development of serologic tests to monitor disease activity and guide treatment. Neural epidermal growth factor-like 1 (NELL1) is the second leading antigen in membranous nephropathy, associated with malignancy, certain medications, and mercury poisoning. Anti-NELL1 antibodies are currently detected within patient sera by western blotting against NELL1 recombinant protein, but no high-throughput clinical assays are available.

Methods: Here, we detail the development of a quantitative ELISA and an indirect immunofluorescence assay for detection of anti-NELL1 antibodies within patient sera and demonstrate that circulating anti-NELL1 antibodies are predominantly IgG1 and IgG4.

Results: These assays had high specificity (94.9%-100%), but relatively low sensitivity (61.3%- 66.7%) compared to the reference standard, defined as biopsy-proven NELL1-positivity. ELISA demonstrated 83.9% overall agreement with the immunofluorescence assay and 82.8% with Western blot, compared to 72.4% overall agreement between the latter two assays.

Conclusions: Our study provides methods for serologic testing to be utilized for serologic evaluation of NELL1-associated membranous nephropathy. Further work will establish if antibody titters correlate with disease activity and response to immunosuppression.

Keywords: NELL1; enzyme-linked immunosorbent assay; indirect immunofluorescence assay; membranous nephropathy; serologic testing.

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Conflict of interest statement

Disclosures: The authors have no conflicts of interest to disclose.

References

    1. Ronco P, Beck L, Debiec H, et al. Membranous nephropathy. Nat Rev Dis Primers. 2021;7(1):69. - PubMed
    1. Beck LH, Bonegio RG, Lambeau G, et al. M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy. N Engl J Med. 2009;361(1):11–21. - PMC - PubMed
    1. Tomas NM, Hoxha E, Reinicke AT, et al. Autoantibodies against thrombospondin type 1 domain-containing 7A induce membranous nephropathy. J Clin Invest. 2016;126(7):2519–32. - PMC - PubMed
    1. Burbelo PD, Joshi M, Chaturvedi A, et al. Detection of PLA2R Autoantibodies before the Diagnosis of Membranous Nephropathy. J Am Soc Nephrol. 2020;31(1):208–17. - PMC - PubMed
    1. Burbelo PD, Olson SW, Keller JM, et al. Prediagnostic Appearance of THSD7A Autoantibodies in Membranous Nephropathy. Kidney360 2022. Nov 29; 4 (2): 217–225. - PMC - PubMed

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