Anti-nephrin antibodies in adult Chinese patients with minimal change disease and primary focal segmental glomerulosclerosis

Abstract

Introduction: Anti-nephrin autoantibodies have been discovered in patients with minimal change disease (MCD) and primary focal segmental glomerulosclerosis (FSGS), especially in those with active nephrotic syndrome.

Methods: Here, we investigated the prevalence and clinical significance of anti-nephrin antibodies in 596 adult Chinese patients (436 with MCD and 160 with primary FSGS) diagnosed by kidney biopsy.

Results: Anti-nephrin IgG and IgM were detected using ELISA, with validation through antigen-inhibition ELISA and Western blotting. Clinical data at biopsy and during the follow-up period were analyzed. Anti-nephrin antibodies were detected in 43% of all patients, with 30% testing positive for anti-nephrin IgG, 26% for anti-nephrin IgM, and 13.1% for both antibodies. The prevalence of anti-nephrin antibodies was higher in patients with nephrotic-range proteinuria who were not receiving steroids or immunosuppressants (51.1%). Patients with positive anti-nephrin antibodies exhibited more severe nephrotic syndrome, higher rates of relapse, and a shorter relapse-free period compared to those negative for these antibodies. Clinical features were similar between those with IgG and IgM. Notably, patients with both anti-nephrin IgG and IgM had the most severe proteinuria and the highest relapse frequency, suggesting a dose-dependent effect. Longitudinal analysis revealed that anti-nephrin antibodies significantly decreased during clinical remission, while they reappeared preceding proteinuria relapse.

Conclusions: Our study shows that anti-nephrin antibodies, including IgG and IgM, are detectable in adult patients with MCD and primary FSGS and are associated with active nephrotic syndrome and frequent relapse. These antibodies may serve as valuable biomarkers and potential therapeutic targets.

Keywords: IgG; IgM; focal segmental glomerulosclerosis; minimal change disease; nephrin.