Abstract: FR-PO0715
When Antibodies Persist: A Case of Graft-vs.-Host Disease-Associated NELL-1 Membranous Nephropathy
Session Information
- Glomerular Diseases: Membranous Nephropathy, FSGS, and Podocytopathies
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
- Mistry, Nupur, Oregon Health & Science University, Portland, Oregon, United States
- Ahn, Wooin, Oregon Health & Science University, Portland, Oregon, United States
- Hocker, Nathaniel J., Oregon Health & Science University, Portland, Oregon, United States
- Stanaway, Madison, Oregon Health & Science University, Portland, Oregon, United States
- Avasare, Rupali S., Oregon Health & Science University, Portland, Oregon, United States
Introduction
The spectrum of autoantigens involved in membranous nephropathy (MN) has expanded with neural epidermal growth factor-like 1 (NELL1) emerging as the second most common antigen after phospholipase A2 receptor. NELL1 is more commonly associated with secondary causes of MN, including graft versus host disease (GVHD). NELL1 MN often responds to cessation of inciting supplements, treatment of underlying conditions, or immunosuppressive (IS) therapy. We report a case of GVHD-associated NELL1 MN refractory to initial B-cell depleting therapy in which measurement of circulating anti-NELL1 antibody provided additional data to support ongoing disease activity.
Case Description
Our patient is a 40-year-old man with acute myeloid leukemia in remission after allogeneic stem cell transplant (aSCT) 11 years prior. Post-aSCT, he developed multiorgan GVHD without renal involvement treated with multiple IS therapies. He presented with 6 months of nephrotic-range proteinuria (UPCr 13 g/g) and edema with preserved kidney function. Kidney biopsy supported a diagnosis of secondary MN with NELL1 positivity on immunohistochemistry.
Despite 2 doses of IV rituximab over 4 weeks in addition to chronic axatilimab, nephrotic-range proteinuria persisted. Three months later, a repeat biopsy was performed for worsening renal function (peak creatinine 9.8 mg/dL), demonstrating ongoing MN and NELL1 positivity. He was initiated on hemodialysis, cyclophosphamide, and plasma exchange (PLEX). Circulating anti-NELL1 antibody testing was performed monthly via Western blot and was used to guide PLEX. After 18 sessions, he was able to discontinue dialysis. However, given ongoing circulating anti-NELL1 antibody, he completed an additional 2 sessions of PLEX and a total of 8 weeks of cyclosporine. Ongoing IS was limited by the development of severe hypogammaglobulinemia (IgG 43.9 mg/dL) and septic arthritis. He was initiated on an angiotensin receptor antagonist and calcineurin inhibitor to limit proteinuria.
Discussion
This case highlights that secondary NELL1 MN can be refractory to standard therapy and require escalation of treatment, including IS and plasma exchange before clinical improvement is achieved. Serial monitoring of circulating NELL1 antibodies may help guide disease activity assessment. Further development of an ELISA test could provide quantitative information on antibody titers to direct tailored immunosuppressive management.