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Abstract: FR-OR093

Prevalence of Exostosin 1/Exostosin 2-Associated Membranous Lupus Nephritis

Session Information

Category: Pathology and Lab Medicine

  • 1602 Pathology and Lab Medicine: Clinical


  • Ravindran, Aishwarya, Mayo Clinic, Rochester, Minnesota, United States
  • Fervenza, Fernando C., Mayo Clinic, Rochester, Minnesota, United States
  • Madden, Benjamin J., Mayo Clinic, Rochester, Minnesota, United States
  • Charlesworth, Cristine, Mayo Clinic, Rochester, Minnesota, United States
  • Sethi, Sanjeev, Mayo Clinic, Rochester, Minnesota, United States

Membranous nephropathy (MN) is classified as primary and secondary. Primary MN is associated with PLA2R antigen in 70-80% cases and THSD7A in 1-5% cases. The target antigens are unknown in 20-25% cases of primary MN and all of secondary MN. Two novel proteins, Exostosin1 and Exostosin 2 (EXT1/EXT2) were recently identified as likely target antigens in a small cohort of MN with an underlying autoimmune etiology (Sethi et al, JASN 2019). In this study, we validate the EXT1/EXT2 findings in a large cohort of patients with lupus membranous nephritis (LMN).


We studied 374 cases of biopsy-proven LMN from 2003 to 2018. Immunohistochemical studies (IHC) using antibodies against EXT1/EXT2 were performed on paraffin-embedded sections. Laser microdissection and mass spectrometry (MS) were performed on a subset of these cases.


Of the 374 LMN cases, 122 (32.6%) were EXT1/EXT2 positive (figure 1) and 252 (67.4%) were EXT1/EXT2 negative by IHC. Among the 122 cases, 86.9% were female. At presentation, the median serum creatinine and proteinuria were 0.8 mg/dL (range: 0.4-14.7) and 4 g/day (range: 0.4-13.5). Kidney biopsies revealed an average of 16.6 glomeruli (SD: ±10.0) with an average of 1.7 globally sclerotic glomeruli (SD: ±3.3). Interstitial fibrosis and tubular atrophy was minimal (<10%) in 89 (72.9%), mild (11-25%) in 21 (17.2%), moderate (26-50%) in 8 (6.6%), and severe (>50%) in 4 (3.3%) cases, respectively. Further, 30 (24.6%) patients had proliferative features (Class III/IV). MS was performed on 8 cases which showed high spectral counts for EXT1 (average: 88.6, SD:± 37.2) and EXT2 (average: 66.1, SD:± 34.6), thus confirming the IHC findings. Among the 252 EXT1/EXT2 negative cases, 81 (32.1%) patients showed proliferative features. MS was performed in 7 of these 252 cases and was negative for EXT1/EXT2.


We validate our previous findings in a large cohort of LMN. Approximately one-third (32.6%) of LMN patients are positive for EXT1/EXT2, of which approximately one-fourth (24.6%) have coexisting proliferative features.

EXT1/EXT2 positive LMN