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Autoantibodies against slit diaphragm proteins such as nephrin and podocin have been identified in subsets of patients, but their prevalence and clinical significance in adult-onset disease are not fully understood. We retrospectively studied 114 adults with biopsy-proven nephrotic syndrome, including minimal change nephrotic syndrome, focal segmental glomerulosclerosis, and phospholipase A2 receptor- and neural epidermal growth factor-like 1-associated membranous nephropathy. Serum anti-nephrin and anti-podocin autoantibodies were quantified using enzyme-linked immunosorbent assays.<\/jats:p>\n                  <jats:p>Anti-nephrin autoantibodies were detected predominantly in minimal change nephrotic syndrome (38.2%) and less frequently in focal segmental glomerulosclerosis (14.3%), but were rare in membranous nephropathy. In contrast, anti-podocin autoantibodies were observed across disease types and were most frequent in neural epidermal growth factor-like 1-associated membranous nephropathy (30.8%). Autoantibody-positive patients presented with more severe nephrotic syndrome, and antibody positivity was associated with a higher incidence of steroid-dependent nephrotic syndrome in exploratory multivariable analyses. In patients with paired samples, autoantibody titers decreased or disappeared in remission.<\/jats:p>\n                  <jats:p>Notably, anti-nephrin antibodies were preferentially associated with MCNS, whereas anti-podocin antibodies were detected across disease entities and may reflect the extent of podocyte injury rather than disease specificity. Moreover, combined assessment of anti-nephrin and anti-podocin antibody status provided improved stratification of baseline disease severity and relapse-prone disease compared with anti-nephrin antibody status alone.<\/jats:p>","DOI":"10.1038\/s41598-026-43612-7","type":"journal-article","created":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T22:44:10Z","timestamp":1773701050000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Autoantibodies against nephrin and podocin are associated with disease severity and steroid dependence in adult-onset nephrotic syndrome"],"prefix":"10.1038","volume":"16","author":[{"given":"Norifumi","family":"Hayashi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryoko","family":"Akai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Kagaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiji","family":"Fujimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takao","family":"Iwawaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitoshi","family":"Yokoyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kengo","family":"Furuichi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,16]]},"reference":[{"issue":"4S","key":"43612_CR1","doi-asserted-by":"publisher","first-page":"S1","DOI":"10.1016\/j.kint.2021.05.021","volume":"100","author":"Kidney Disease: Improving Global Outcomes Glomerular Diseases Work G","year":"2021","unstructured":"Kidney Disease: Improving Global Outcomes Glomerular Diseases Work G. KDIGO 2021 clinical practice guideline for the management of glomerular diseases. Kidney Int. 100(4S), S1\u2013S276. https:\/\/doi.org\/10.1016\/j.kint.2021.05.021 (2021).","journal-title":"Kidney Int."},{"issue":"3","key":"43612_CR2","doi-asserted-by":"publisher","first-page":"502","DOI":"10.2215\/CJN.05960616","volume":"12","author":"AZ Rosenberg","year":"2017","unstructured":"Rosenberg, A. Z. & Kopp, J. B. Focal segmental glomerulosclerosis. Clin. J. Am. Soc. Nephrol. 12(3), 502\u2013517. https:\/\/doi.org\/10.2215\/CJN.05960616 (2017).","journal-title":"Clin. J. Am. Soc. Nephrol."},{"issue":"5","key":"43612_CR3","doi-asserted-by":"publisher","first-page":"1139","DOI":"10.2215\/CJN.05260610","volume":"6","author":"S Santin","year":"2011","unstructured":"Santin, S. et al. Clinical utility of genetic testing in children and adults with steroid-resistant nephrotic syndrome. Clin. J. Am. Soc. 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