Raglianti, ValentinaAngelotti, Maria LuciaCirillo, LuigiRavaglia, FiammettaLandini, SamuelaPalazzo, VivianaMelica, Maria ElenaAntonelli, GiuliaConte, CarolinaButi, ElisaErrichiello, CarmelaDe Chiara, LetiziaPeired, Anna JulieLasagni, LauraBuccoliero, Anna MariaAllinovi, MarcoManonelles Montero, AnnaCruzado, Josep Ma.Bruschi, MaurizioGhiggeri, Gian MarcoAngeletti, AndreaAnders, Hans-JoachimLazzeri, ElenaMazzinghi, BenedettaBecherucci, FrancescaRomagnani, Paola2025-03-272025-03-272024-12-010085-2538https://hdl.handle.net/2445/220069Podocytopathies represent a group of glomerular disorders associated with minimal changes (MC) or focal segmental glomerulosclerosis (FSGS) lesion patterns at biopsy and heterogeneous responses to steroids. Anti-nephrin antibodies were previously found in such patients, suggesting an autoimmune form of podocytopathy. High resolution confocal microscopy on kidney biopsies of a cohort of 128 pediatric patients revealed localization of IgG along the slit diaphragm in 30% of patients with MC and 25% of those with FSGS, but not in other lesion patterns. Anti-nephrin IgG ELISA assay in the serum and stimulated emission depletion microscopy of kidney biopsies showed IgG-nephrin co-localization only in 77.8% of cases. Similar observations were obtained in a cohort of 48 adult patients with MC or FSGS at kidney biopsy, where IgG-nephrin colocalization was only 44.4%, suggesting the existence of autoantibodies binding to other slit proteins. Patients with anti-slit antibodies showed nephrotic syndrome at onset in 94.4% of cases. Patients with primary steroid-resistance had anti-slit antibodies in 27%, while those with secondary steroid-resistance in 87.5% of cases, irrespective of the histopathological lesion pattern. Steroid-resistant patients with anti-slit antibodies responded to second-line immunosuppressants in 92.3% vs. only 20% of patients that were anti-slit negative. No patient with anti-slit antibodies developed kidney failure vs. 51.7% of those negative for antibodies (66.7% with a genetic cause and 41.2% with a non-genetic cause). Thus, the detection of anti-slit antibodies can identify patients with an autoimmune podocytopathy responsive to treatment with second-line immunosuppressants, irrespective of the histopathological lesion pattern at biopsy.11 p.application/pdfengcc-by (c) Raglianti, Valentina et al., 2024https://creativecommons.org/licenses/by/4.0/InfantsBiòpsiaResistència als medicamentsAutoanticossosChildrenBiopsyDrug resistanceAutoantibodiesinfo:eu-repo/semantics/article7530502025-03-27info:eu-repo/semantics/openAccess39368741