Passive transfer of patient-derived anti-nephrin autoantibodies causes a podocytopathy with minimal change lesions

To the editor: Autoantibodies against nephrin, a key podocyte signaling protein forming the slit diaphragm between podocyte foot processes, were recently identified in a major portion of patients with podocytopathies (1, 2). Anti-nephrin autoantibodies strongly correlate with disease activity in these patients, and nephrin-immunized mice develop anti-nephrin antibodies, alterations in nephrin phosphorylation, podocyte ultrastructure, and nephrotic syndrome, suggesting pathogenicity of these autoantibodies (1). However, a pathogenic role of human anti-nephrin autoantibodies in the development of a podocytopathy has not been demonstrated. A 71-year-old female developed a rapid-onset nephrotic syndrome and was diagnosed with minimal change disease (MCD) by kidney biopsy (Figure 1, A and B and Supplemental Material; supplemental material available online with this article; https://doi.org/10.1172/JCI186769DS1). We found high circulating anti-nephrin autoantibody levels (1) at the time of exacerbating nephrotic syndrome and low autoantibody levels at the time of partial remission (Figure 1A, red line), illustrating the strong association of anti-nephrin autoantibodies with disease activity in patients with anti-nephrin–associated podocytopathy. Using immunoprecipitation (IP) and subsequent Western blotting, we detected low crossreactivity of patient anti-nephrin autoantibodies with