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Abstract: TH-PO453

Neuron-Derived Neurotrophic Factor (NDNF) Is a Novel Protein Associated With Membranous Nephropathy (MN)

Session Information

Category: Glomerular Diseases

  • 1302 Glomerular Diseases: Immunology and Inflammation

Authors

  • Sethi, Sanjeev, Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
  • Madden, Benjamin J., Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
  • Fervenza, Fernando C., Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
  • Haas, Mark, Cedars-Sinai Medical Center, Los Angeles, California, United States
Background

Primary MN is commonly associated with antibodies to target antigen PLA2R. The other target antigens in primary MN include THSD7A, NELL1, SEMA3B, HTRA1 and PCDH7. Taken together, these antigens account for approximately 80-90% of primary MN. The target antigen is unknown in the remaining 10-20% primary MN.

Methods

We performed laser microdissection of glomeruli followed by mass spectrometry (MS) in 250 cases of PLA2R-negative MN to identify novel antigenic targets in MN. This was followed by immunohistochemistry (IHC) to localize the target antigen along the glomerular basement membrane (GBM). Western blot analyses were performed to detect antibodies to novel antigen using serum/IgG eluate of frozen biopsy tissue.

Results

MS studies revealed high total spectral counts (average 29.6, range 19-36) of a novel protein Neuron-derived neurotrophic factor (NDNF) in 3 (1.6%) of the 250 cases (Fig 1). All cases were negative for known antigens including PLA2R, THSD7A, EXT1/EXT2, NELL1, SEMA3B, PCDH7, FAT1, CNTN1 and NCAM1. The median age was 53 years (range 30-73), serum creatinine 3.1 mg/dL (1.4-10), proteinuria 9.7 gms/day (3.1-11) at presentation. One patient had history of HIV and NSAID use, with the biopsy showing acute interstitial nephritis in addition to MN. All cases showed IgG (2-3+) and C3 (2-3+) along GBM, tubular atrophy and interstitial fibrosis was less than 20%, and EM showed stage I-II in all cases. IHC showed granular staining for NDNF along the GBM (Fig 2), control cases were negative. Western blot studies are ongoing.

Conclusion

NDNF is a likely novel antigenic target in primary MN.

MS studies show high total spectral counts of novel protein NDNF in 3 cases, IgG with higher counts of IgG1 and IgG3, and C3.

IHC shows granular staining for NDNF along the GBM in a case of NDNF-associated MN.