Anti-CD20 therapies and anti-nephrin autoantibodies in IgA nephropathy with minimal change disease

Abstract Introduction In IgA nephropathy with minimal change disease (MCD-IgAN), the efficacy of anti-CD20 monoclonal antibodies (mAbs) and the profile of anti-nephrin antibodies remain poorly understood. Methods We evaluated the efficacy of anti-CD20 mAbs or combined short-course low-dose steroids (anti-CD20 mAbs group) compared to full-dose prolonged steroids (steroids group) and assessed the prevalence of anti-nephrin antibodies in a retrospective cohort of MCD-IgAN patients. Results Total remission rates of nephrotic syndrome were comparable between anti-CD20 mAbs group and steroids group in 45 adult MCD-IgAN patients. Notably, anti-CD20 mAbs group achieved a longer recurrence-free period after complete remission compared to steroids group (median 30.4 vs. 17.1 months, p=0.01). In addition, patients in anti-CD20 mAbs group experienced significantly fewer total adverse events and re-hospitalization rates. Circulating anti-nephrin antibodies was detected in 31.1% (19/61) of MCD-IgAN patients, comparable to MCD patients. Furthermore, patients with anti-nephrin antibodies more than 150 ng/mL exhibited significantly increased hazard risk of recurrence (HR=3.93, 95% CI: 1.18-13.13), higher recurrence rate per person-year (IRR 3.16, 95%CI: 1.42-7.03) and shorter relapse-free interval compared to those with lower anti-nephrin antibodies (median 14.0 vs. 48.3 months, p=0.02). Importantly, anti-nephrin antibody levels in sequential plasma samples closely tracked clinical course of disease remission and relapses during follow-up. Conclusion Our findings indicated anti-CD20 mAbs represented an effective and safe therapeutic option for adult patients with MCD-IgAN. Circulating anti-nephrin antibodies were detectable and associated with a higher relapse rate, suggesting its potential utility as a biomarker of both disease activity and therapeutic target in this disease.