Anti-slit diaphragm antibodies on kidney biopsy identify pediatric patients with steroid-resistant nephrotic syndrome responsive to second-line immunosuppressants.

Autor:	Raglianti V; Nephrology and Dialysis Unit, Meyer Children's Hospital IRCCS, Florence, Italy; Department of Biomedical, Experimental and Clinical Sciences 'Mario Serio,' University of Florence, Florence, Italy., Angelotti ML; Department of Biomedical, Experimental and Clinical Sciences 'Mario Serio,' University of Florence, Florence, Italy., Cirillo L; Nephrology and Dialysis Unit, Meyer Children's Hospital IRCCS, Florence, Italy; Department of Biomedical, Experimental and Clinical Sciences 'Mario Serio,' University of Florence, Florence, Italy., Ravaglia F; Nephrology and Dialysis Unit, Santo Stefano Hospital, Prato, Italy., Landini S; Medical Genetics Unit, Meyer Children's Hospital IRCCS, Florence, Italy., Palazzo V; Medical Genetics Unit, Meyer Children's Hospital IRCCS, Florence, Italy., Melica ME; Department of Biomedical, Experimental and Clinical Sciences 'Mario Serio,' University of Florence, Florence, Italy., Antonelli G; Nephrology and Dialysis Unit, Meyer Children's Hospital IRCCS, Florence, Italy., Conte C; Nephrology and Dialysis Unit, Meyer Children's Hospital IRCCS, Florence, Italy., Buti E; Nephrology and Dialysis Unit, Meyer Children's Hospital IRCCS, Florence, Italy., Errichiello C; Nephrology and Dialysis Unit, Meyer Children's Hospital IRCCS, Florence, Italy., De Chiara L; Department of Biomedical, Experimental and Clinical Sciences 'Mario Serio,' University of Florence, Florence, Italy., Peired AJ; Department of Biomedical, Experimental and Clinical Sciences 'Mario Serio,' University of Florence, Florence, Italy., Lasagni L; Department of Biomedical, Experimental and Clinical Sciences 'Mario Serio,' University of Florence, Florence, Italy., Buccoliero AM; Pathology Unit, Meyer Children's Hospital IRCCS, Florence, Italy., Allinovi M; Nephrology, Dialysis and Transplantation Unit, Careggi University Hospital AUOC, Florence, Italy., Montero AM; Renal Transplant Unit, Nephrology Department, Bellvitge University Hospital, Barcelona, Spain., Cruzado JM; Renal Transplant Unit, Nephrology Department, Bellvitge University Hospital, Barcelona, Spain., Bruschi M; UO Nephrology Dialysis and Transplant, IRCCS Istituto Giannina Gaslini, Genoa, Italy., Ghiggeri GM; UO Nephrology Dialysis and Transplant, IRCCS Istituto Giannina Gaslini, Genoa, Italy., Angeletti A; UO Nephrology Dialysis and Transplant, IRCCS Istituto Giannina Gaslini, Genoa, Italy., Anders HJ; Division of Nephrology, Medizinische Klinik and Poliklinik IV, Klinikum der LMU München, Munich, Germany., Lazzeri E; Department of Biomedical, Experimental and Clinical Sciences 'Mario Serio,' University of Florence, Florence, Italy., Mazzinghi B; Nephrology and Dialysis Unit, Meyer Children's Hospital IRCCS, Florence, Italy., Becherucci F; Nephrology and Dialysis Unit, Meyer Children's Hospital IRCCS, Florence, Italy; Department of Biomedical, Experimental and Clinical Sciences 'Mario Serio,' University of Florence, Florence, Italy., Romagnani P; Department of Biomedical, Experimental and Clinical Sciences 'Mario Serio,' University of Florence, Florence, Italy. Electronic address: paola.romagnani@meyer.it.
Jazyk:	angličtina
Zdroj:	Kidney international [Kidney Int] 2024 Oct 03. Date of Electronic Publication: 2024 Oct 03.
DOI:	10.1016/j.kint.2024.09.006
Abstrakt:	Podocytopathies 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. (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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