Kidney Week

Abstract: FR-OR093

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

Session Information

• New Techniques and Breakthroughs in Renal Pathology
  November 08, 2019 | Location: Salon A/B, Walter E. Washington Convention Center
  Abstract Time: 04:54 PM - 05:06 PM

Category: Pathology and Lab Medicine

• 1602 Pathology and Lab Medicine: Clinical

Authors

• Ravindran, Aishwarya, Mayo Clinic, Rochester, Minnesota, United States

Aishwarya Ravindran, MBBS



I am a medical graduate from Stanley medical college, India. I am currently pursuing my third-year residency in Anatomic/Clinical Pathology at Mayo Clinic, Rochester, MN. My research interests include monoclonal protein disorders of the kidney, analyzing proteomics and understanding the complement pathways of rare renal disorders like C3 glomerulopathy and thrombotic microangiopathies. My career goal is to become an academic pathologist complemented by my passion for understanding the complex pathological processes, which will drive me to be involved in research projects and education of the next generation of trainees throughout my future career.

• Fervenza, Fernando C., Mayo Clinic, Rochester, Minnesota, United States

Fernando C. Fervenza,

• Madden, Benjamin J., Mayo Clinic, Rochester, Minnesota, United States

Benjamin J. Madden,

• Charlesworth, Cristine, Mayo Clinic, Rochester, Minnesota, United States

Cristine Charlesworth,

• Sethi, Sanjeev, Mayo Clinic, Rochester, Minnesota, United States

Sanjeev Sethi,

Background

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).

Methods

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.

Results

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.

Conclusion

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