Single-Center Experience with Exostosin-2 Immunohistochemical Staining in Lupus Membranous Nephropathy

Background: In lupus membranous nephropathy (LMN), Exostosin-2 (EXT2) is a potential disease antigen. Compared with EXT2-negative cases, EXT2-positive LMN likely represents a subgroup with favorable kidney biopsy findings with respect to chronicity indices and are less likely to progress to kidney failure. We describe a single center experience of LMN stratified by EXT2 status at initial presentation. Methods: We conducted a retrospective cohort study of patients with MLN and performed an immunohistochemistry (IHC) study on the kidney biopsy specimen against EXT2. Clinicopathological features in LMN patients with EXT2- positive versus negative IHC staining were compared. Results: Among 10 LMN patients at initial presentation, 4 were EXT2-positive (40%) and 6 were EXT2-negative (Table 1). Those with EXT2 positivity were all Black females, younger, and had a higher baseline serum creatinine. They all had hematuria and higher proteinuria (including nephrotic-range) at baseline. All EXT2-positive patients had lower chronicity features although 50% had additional proliferative lesions associated with lupus. Electron microscopy revealed a higher rate of subendothelial, mesangial, subepithelial, and intramembranous deposits in EXT2-positive cases. Conclusion: At our center, 40% of LMN patients had EXT2 positivity comparable to that described in the medical literature. Interestingly, our patients had a higher baseline creatinine, proteinuria, and additional proliferative lesions. However, despite this, their kidney biopsies demonstrated lesser scarring and chronicity features which aligns with the current notion that in EXT positive LMN, the increased secretion of EXT into the glomerular basement membrane (GBM) likely results in increased local synthesis of heparan sulfates which adds to their stability and may offer protection from downstream damaging events.