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Abstract: FR-PO671

Novel Target Antigens in Sarcoidosis-Associated Membranous Nephropathy

Session Information

Category: Glomerular Diseases

  • 1302 Glomerular Diseases: Immunology and Inflammation

Authors

  • Nardelli, Luca, Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
  • Zubidat, Dalia, 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
  • Kudose, Satoru, Columbia University, New York, New York, United States
  • Negron, Vivian C., Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
  • Gross, Louann, Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
  • Nasr, Samih H., 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
  • Sethi, Sanjeev, Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
Background

Kidney involvement occurs in 10-20% patients with sarcoidosis. Membranous nephropathy (MN) is the most frequent glomerular disease in patients with sarcoidosis. Previous small case series have shown that greater than 50% of MN diagnosed in patients with sarcoidosis are positive for Phospholipase A2 receptor (PLA2R). However, no target antigens have been identified in the remaining sarcoidosis-associated MN.

Methods

We performed a retrospective study of 19 patients diagnosed with sarcoidosis and biopsy-proven MN. We performed laser microdissection of glomeruli followed by mass-spectrometry (MS/MS) to detect MN antigens. This was followed by immunohistochemistry (IHC)/ immunofluorescence microscopy (IF) staining to confirm and localize the antigens.

Results

Using MS/MS, we identified PLA2R in 7/19 (37%), neural epidermal growth factor-like 1 protein (NELL1) in 4/19 (21%), and 1/19 (5%) each of thrombospondin type 1 domain-containing 7A (THSD7A) antigen, protocadherin 7 (PDCH7) and Proprotein Convertase Subtilisin/Kexin Type 6 (PCSK6/abstract submitted) (Fig 1) . IHC/IF confirmed MS/MS findings and showed PLA2R, NELL1, THSD7A and PDCH7 staining along the GBM (Fig 2). Segmental NELL1 staining was noted in 2 of the 4 NELL1-positive MN. No known antigen was detected in the remaining 5/19 (26%) MN cases.

Conclusion

The presence of PLA2R antigen in renal biopsy should not exclude a secondary cause of MN, particularly sarcoidosis. The incidence of PLA2R-negative MN associated with sarcoidosis is probably higher than what has been previously reported. NELL1, PDCH7, THSD7A, and PCSK6 represent new antigens in sarcoidosis-associated MN.

Target antigens in Sarcoidosis-associated MN.

IHC showing granular GBM staining for (A-E) NELL1 in 4 cases, panel C shows segmental GBM staining, arrow points to few loops showing no staining (C and D are same case) and (F) PCDH7.