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Abstract: PO1538

Clinical Relevance of NELL1 Antibodies in Patients with Membranous Nephropathy

Session Information

Category: Glomerular Diseases

  • 1203 Glomerular Diseases: Clinical, Outcomes, and Trials


  • Reinhard, Linda, Universitatsklinikum Hamburg-Eppendorf, Hamburg, Hamburg, Germany
  • Krümpelmann, Benedikt, Universitatsklinikum Hamburg-Eppendorf, Hamburg, Hamburg, Germany
  • Wiech, Thorsten, Universitatsklinikum Hamburg-Eppendorf, Hamburg, Hamburg, Germany
  • Stahl, Rolf A., Universitatsklinikum Hamburg-Eppendorf, Hamburg, Hamburg, Germany
  • Hoxha, Elion, Universitatsklinikum Hamburg-Eppendorf, Hamburg, Hamburg, Germany

NELL1 was identified as a potential novel target antigen in membranous nephropathy (MN). Here, we studied the association of NELL1-antibody (ab) with treatment response and prognosis in a large cohort of MN patients.


Circulating NELL1-ab were detected by Western blot in a prospective cohort of 87 PLA2R- and THSD7A-ab negative MN patients, 130 PLA2R- or THSD7A-ab positive MN patients and 116 control patients with a biopsy-proven GN other than MN. Clinical follow-up included treatment, remission or relapse of proteinuria and development of kidney function.


NELL1-ab were identified in 18 (21%) patients with PLA2R- and THSD7A-ab negative MN but none of the control cohorts’ patients. We identified NELL1-specific IgG1, IgG2, IgG3 and IgG4 subclasses in the serum of 12 (67%), 7 (39%), 11 (61%) and 15 (83%) NELL1-ab positive patients, respectively. NELL1-ab positive patients were significantly (p<0.05) older compared to PLA2R-ab positive patients or MN patients without known target antigen (median age 70 vs 58 vs 58 years). Within 6 months of MN diagnosis, a malignant tumor was identified in 2 (11%) NELL1-ab positive, 7 (6%) PLA2R-ab positive, 3 (50%) THSD7A-ab positive and 7 (10%) MN patients without known target antigen.
14 NELL1-ab positive patients were observed over a median follow-up of 75 months. One patient presented with eGFR < 30 ml/min due to severe hypertensive and diabetic kidney damage and developed ESKD after 69 months. All other 13 patients had a remission of proteinuria. 12 (92%) patients had a complete remission, although only 4 patients received an immunosuppressive therapy. Remarkably, of the 9 untreated patients with complete remission of proteinuria, 4 patients had persisting NELL1-ab in the circulation over the whole observation period and 2 patients reached complete remission of proteinuria before NELL1-ab disappeared. Renal function was stable in NELL1-ab positive patients but showed a more pronounced decline in NELL1-ab negative patients.


NELL1-ab positive MN patients had slightly more often a malignant tumor, but also were significantly older compared to PLA2R-ab positive patients. Overall, NELL1-ab positive patients had a good prognosis. The presence of NELL1-ab in the serum did not show a close association with disease outcome.


  • Government Support – Non-U.S.