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

The identification of autoantibodies against nephrin, a key signaling 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 with immune cell subsets and therapy response remain to be determined.

In this prospective study, we evaluated blood samples from adults with newly diagnosed, biopsy-proven MCD for circulating anti-nephrin antibodies using immunoprecipitation (IP) and B-cell subpopulations by fluorescence-activated cell sorting. Samples were collected at diagnosis (t₀) and after 8 weeks of steroid therapy (t₁).

We detected anti-nephrin antibodies in 12 of 17 (70.6%) therapy-naïve patients with MCD at t₀. All 12 patients (100%) positive for anti-nephrin antibodies achieved complete remission with no anti-nephrin antibodies detectable after 8 weeks of steroid treatment (t₁). Two of 5 anti-nephrin negative patients (40%) did not reach clinical remission at t₁. Anti-nephrin positive patients exhibited a larger fraction of plasmablasts than anti-nephrin negative patients at t₀, albeit not statistically significant. Plasmablasts, naïve B cells, and transitional B cells significantly decreased, whereas marginal zone-like B cells increased within 8 weeks of steroid treatment in anti-nephrin positive patients (t₁).

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.