Detection and characterization of NELL1 autoantibodies in NELL1 positive membranous nephropathy.
| Title: | Detection and characterization of NELL1 autoantibodies in NELL1 positive membranous nephropathy. |
|---|---|
| Authors: | Caza TN; Arkana Laboratories, Little Rock, Arkansas, USA. Electronic address: tiffany.caza@arkanalabs.com.; Arivett BA; Department of Microbiology, Immunology and Physiology, Meharry Medical College, Nashville, Tennessee, USA.; Hassen SI; Arkana Laboratories, Little Rock, Arkansas, USA.; Al-Rabadi LF; Division of Nephrology, Department of Internal Medicine, University of Utah Medical Center, Salt Lake City, Utah, USA.; Takayama S; Division of Nephrology, Department of Internal Medicine, University of Utah Medical Center, Salt Lake City, Utah, USA.; Ibrahim A; Division of Nephrology, Department of Internal Medicine, University of Utah Medical Center, Salt Lake City, Utah, USA.; Larsen CP; Arkana Laboratories, Little Rock, Arkansas, USA.; Borza DB; Department of Microbiology, Immunology and Physiology, Meharry Medical College, Nashville, Tennessee, USA. Electronic address: dborza@mmc.edu. |
| Source: | Kidney international [Kidney Int] 2025 Sep; Vol. 108 (3), pp. 427-432. Date of Electronic Publication: 2025 Jun 18. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Elsevier Country of Publication: United States NLM ID: 0323470 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1523-1755 (Electronic) Linking ISSN: 00852538 NLM ISO Abbreviation: Kidney Int Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2016- : New York : Elsevier; Original Publication: New York, Springer-Verlag. |
| MeSH Terms: | Autoantibodies*/blood ; Glomerulonephritis, Membranous*/immunology ; Glomerulonephritis, Membranous*/blood ; Glomerulonephritis, Membranous*/diagnosis ; Nerve Tissue Proteins*/immunology ; Autoantigens*/immunology; Immunoglobulin G/blood ; Humans ; Enzyme-Linked Immunosorbent Assay ; Calcium-Binding Proteins ; Fluorescent Antibody Technique, Indirect ; Blotting, Western ; Female ; Male ; Middle Aged ; Predictive Value of Tests ; Adult ; Sensitivity and Specificity |
| 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.; (Copyright © 2025 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.) |
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| Grant Information: | R21 HL168484 United States HL NHLBI NIH HHS; R44 DK130702 United States DK NIDDK NIH HHS; U54 MD007586 United States MD NIMHD NIH HHS; UG3 HG013248 United States HG NHGRI NIH HHS |
| Contributed Indexing: | Keywords: NELL1; enzyme-linked immunosorbent assay; indirect immunofluorescence assay; membranous nephropathy; serologic testing |
| Substance Nomenclature: | 0 (Autoantibodies); 0 (NELL1 protein, human); 0 (Nerve Tissue Proteins); 0 (Calcium-Binding Proteins); 0 (Immunoglobulin G); 0 (Autoantigens) |
| Entry Date(s): | Date Created: 20250620 Date Completed: 20250822 Latest Revision: 20251217 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC12705032 |
| DOI: | 10.1016/j.kint.2025.05.025 |
| PMID: | 40541723 |
| Database: | MEDLINE |
Journal Article