Abstract: FR-PO0811
NELL-1 Membranous Nephropathy Is Associated with HLA-DRB1*13: A Pilot Study of 10 Patients
Session Information
- Glomerular Diseases: Practice and New Concepts Shaping Modern Care
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Avasare, Rupali S., Oregon Health & Science University, Portland, Oregon, United States
- Stanaway, Madison, Oregon Health & Science University, Portland, Oregon, United States
- Shaut, Carley, Oregon Health & Science University, Portland, Oregon, United States
Background
Neural epidermal growth factor-like 1 (NELL1) membranous nephropathy (MN) is characterized by proteinuria, edema, circulating anti-NELL1 antibody, and glomerular immune deposits consisting of immunoglobulin G (usually IgG1) and NELL1. NELL1 MN occurs most commonly in adults aged 60s and is associated with lipoic acid supplementation or cancer. How these clinical conditions promote NELL1-specific immune dysregulation is unknown. We hypothesize CD4+ helper T cells are involved in NELL1 MN pathogenesis, because CD4+ T cells direct B cells to produce antibodies, in particular IgG1 antibodies. In order to direct B cells, CD4+ T cells must be activated by antigen loaded on specific human leukocyte antigen (HLA) class II molecules. Here, we aim to discover whether NELL1 MN patients harbor specific HLA class II alleles in a pilot study.
Methods
Patients with NELL1 membranous nephropathy were consented and enrolled in our institutional kidney disease biorepository. Demographic data and associated secondary conditions (lipoic acid, cancer, or other) were recorded. HLA typing was performed on whole blood samples at HLA-DRB1, DRB345, DQA1, DQB1, DPA1, and DPB1 by next-generation sequencing (GenDX NGSgo-MX11.3 typing kit on the Illumina MiSEQ platform). Allele frequency was measured and compared to the general population (USA Caucasians; allelefrequencies.net) using Fishers Exact test.
Results
HLA typing was performed on 10 patients, of whom 5 are female, 6 use lipoic acid, 2 have active cancer, 2 have a history of stem cell transplant for acute myeloid leukemia, and all are white race (self-reported). Seven of 10 patients are positive for HLA-DRB1*13 (of whom 5 are DRB1*13:01-DQB1*06:03, haplotype inferred by common associations) compared to 23% in the general population, p <0.004.
Conclusion
We report the first ever analysis of HLA class II alleles in a pilot cohort of patients with NELL1 MN associated with lipoic acid, cancer, or other conditions. HLA-DRB1*13 is strongly associated with NELL1 MN in patients with various secondary disease associations. This novel preliminary data supports a role for CD4+ T cells in NELL1 MN and provides rationale for future studies investigating NELL1as a CD4+ T cell antigen.
Acknowledgment
NIH Funding: K23DK135855
Funding
- NIDDK Support