Effect of Steroids on Anti-nephrin Autoantibodies and B cells in Minimal Change Disease

Introduction The identification of autoantibodies against nephrin, a key signalling protein of the podocyte slit diaphragm, and their pathogenic role in patients with minimal change disease (MCD) has substantially changed our understanding of primary podocytopathies. However, details on underlying immune pathophysiological mechanisms such as the relation of anti-nephrin autoantibodies to immune cell subsets and therapy response remain to be determined. Methods In this prospective study, we evaluated blood samples from adults with newly diagnosed, biopsy-proven MCD for circulating anti-nephrin antibodies using immunoprecipitation and B cell subpopulations by fluorescence-activated cell sorting. Samples were collected at diagnosis (t 0 ) and after 8 weeks of steroid therapy (t 1 ). Results We detected anti-nephrin antibodies in 12/17 (70.6%) therapy-naïve patients with MCD at t 0 . All 12 (100%) patients positive for anti-nephrin antibodies achieved complete remission with no anti-nephrin antibodies detectable after 8 weeks of steroid treatment (t 1 ). Two out of 5 (40%) anti-nephrin negative patients did not reach clinical remission at t 1 . Anti-nephrin positive patients exhibited a larger fraction of plasmablasts than anti-nephrin negative patients at t 0 , albeit not statistically significant. Plasmablasts, naïve B cells and transitional B cells significantly decreased, while marginal zone-like B cells increased within 8 weeks of steroid treatment in anti-nephrin positive patients (t 1 ). Conclusion Our study shows, for the first time, a therapeutically relevant short-term effect of steroids on the B cell compartment and anti-nephrin antibody levels, explaining the high clinical response rate in patients with anti-nephrin-associated MCD.