Disease-Specific Prevalence and Clinical Significance of Antinephrin Autoantibodies in Adult Japanese Patients with Podocytopathy: A Single-Center Cohort Study, 2016-2024

Background: Anti-nephrin autoantibodies (ANeph-Ab) are proposed pathogenic antigens in podocyte injury, yet data in adult Asian populations are lacking. We aimed to investigate disease-specific prevalence, association with immunosuppressive therapy timing, and clinical significance of ANeph-Ab in adult Japanese podocytopathy. Methods: We retrospectively analyzed 57 adults diagnosed via kidney biopsy (2016–2024): 32 with minimal change nephrotic syndrome (MCNS), 20 with secondary FSGS, and 5 with primary FSGS. Age and sex were recorded. Serum collected at biopsy admission was tested via indirect ELISA using full-length human nephrin (1:400; anti-human IgG-HRP 1:2000), with a positivity cutoff of 226 U/mL. Outcomes included disease-specific positivity, timing relative to therapy, time to remission, and frequent relapse (FR) in MCNS. Results: ANeph-Ab positivity was 18.8% in MCNS, 20.0% in secondary FSGS, and 60.0% in primary FSGS (p = 0.12). In MCNS, no patients were positive pre-therapy (0/4), while 21% were positive post-therapy (6/28). In secondary FSGS, 24% were positive pre-therapy (4/17) and 0% post-therapy. In primary FSGS, 0% (0/1) were positive pre-therapy, 75% (3/4) post-therapy. Time to remission was shorter in the antibody-positive group (median 17 vs 28 days, p = 0.60). In MCNS, FR occurred in 0% of antibody-positive vs 38% of negative cases (p = 0.04). Conclusion: Most ANeph-Ab-positive MCNS cases were identified post-therapy, suggesting treatment-induced seronegativity and potential underestimation of true prevalence. The absence of FR among ANeph-Ab-positive MCNS cases supports a treatment-sensitive subtype. High positivity and brisk response in primary FSGS support immune-mediated injury. Some secondary FSGS cases also showed features suggestive of immune involvement. This is the first adult Asian cohort systematically evaluating ANeph-Ab prevalence and therapeutic context in podocytopathy.