Clinical and Outcomes Correlations with Exostosin 1 Positivity Lupus Nephritis

Background: Recently, exostosin 1 (EXT1) and exostosin 2 (EXT2), were identified in patients with lupus membranous nephropathy (LMN). Immunohistochemical studies revealed positivity rates from 32.6% to 46%, and these patients present lower chronicity indexes and reduced chronic kidney disease (CKD) progression but are more likely to disclose massive proteinuria at diagnosis. Follow-up results are conflicting, but patients with positive EXT1/EXT2 LMN had a lower incidence of end-stage kidney disease (ESKD) compared to those with negative EXT1/EXT2 LMN. The aim of this study was to assess the prevalence of EXT1/EXT2 in renal biopsies of patients with LMN (class V) and LMN with proliferative component (class III/IV + V), comparing clinicopathologic features at diagnosis and outcomes in patients followed for at least 2 years. Methods: A retrospective cohort study of patients with membranous lupus nephritis was performed and EXT 1 immunohistochemistry studies on the kidney biopsy specimens were evaluated. (Picture 1). Clinicopathologic features and outcomes of EXT1 positive versus EXT1 negative patients were compared. Results: Our cohort included 94 patients, of which 34 (36%) were EXT1 positive. According to histological classification, 13 out of 31 (41.94%) patients with LMN were EXT1 positive and 21 out of 63 (33%) patients with LNM associated with proliferation were EXT 1 positive (Picture 2). There were not significant differences between EXT 1 positive and negative groups at the time of renal biopsy, regarding proteinuria and serum creatinine levels, and also activity or chronicity indices on kidney biopsy. A total of 85 patients were followed for a median of 50 months. Patients with EXT1 positive showed significantly higher rates of complete or partial treatment response (p=0.035) and negative anti-DNA antibodies (p=0.01). Conclusion: The prevalence of EXT1 positivity in LMN was 36% in our cohort. No differences were observed at diagnosis presentation, however, patients with positive EXT1 had better treatment response rates and lower anti-DNA antibodies levels, suggesting a more favorable prognosis for these patients.