Modeling a biofluid-derived extracellular vesicle surface signature to differentiate pediatric idiopathic nephrotic syndrome clinical subgroups
Abstract Idiopathic Nephrotic Syndrome (INS) is a common childhood glomerular disease requiring intense immunosuppressive drug treatments. Prediction of treatment response and the occurrence of relapses remains challenging. Biofluid-derived extracellular vesicles (EVs) may serve as novel liquid biop...
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Nature Portfolio
2024-10-01
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| Online Access: | https://doi.org/10.1038/s41598-024-76727-w |
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| author | Giulia Cricri Andrea Gobbini Stefania Bruno Linda Bellucci Sarah Tassinari Federico Caicci Chiara Tamburello Teresa Nittoli Irene Paraboschi Alfredo Berrettini Renata Grifantini Benedetta Bussolati William Morello Giovanni Montini Federica Collino |
| author_facet | Giulia Cricri Andrea Gobbini Stefania Bruno Linda Bellucci Sarah Tassinari Federico Caicci Chiara Tamburello Teresa Nittoli Irene Paraboschi Alfredo Berrettini Renata Grifantini Benedetta Bussolati William Morello Giovanni Montini Federica Collino |
| author_sort | Giulia Cricri |
| collection | DOAJ |
| description | Abstract Idiopathic Nephrotic Syndrome (INS) is a common childhood glomerular disease requiring intense immunosuppressive drug treatments. Prediction of treatment response and the occurrence of relapses remains challenging. Biofluid-derived extracellular vesicles (EVs) may serve as novel liquid biopsies for INS classification and monitoring. Our cohort was composed of 105 INS children at different clinical time points (onset, relapse, and persistent proteinuria, remission, respectively), and 19 healthy controls. The expression of 37 surface EV surface markers was evaluated by flow cytometry in serum (n = 83) and urine (n = 74) from INS children (mean age = 10.1, 58% males) at different time points. Urine EVs (n = 7) and serum EVs (n = 11) from age-matched healthy children (mean age = 7.8, 94% males) were also analyzed. Tetraspanin expression in urine EVs was enhanced during active disease phase in respect to the remission group and positively correlates with proteinuria levels. Unsupervised clustering analysis identified an INS signature of 8 markers related to immunity and angiogenesis/adhesion processes. The CD41b, CD29, and CD105 showed the best diagnostic scores separating the INS active phase from the healthy condition. Interestingly, combining urinary and serum EV markers from the same patient improved the precision of clinical staging separation. Three urinary biomarkers (CD19, CD44, and CD8) were able to classify INS based on steroid sensitivity. Biofluid EVs offer a non-invasive tool for INS clinical subclassification and “personalized” interventions. |
| format | Article |
| id | doaj-art-dc611bf76e4c463db0a0a87791899b92 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-dc611bf76e4c463db0a0a87791899b922024-12-08T12:25:23ZengNature PortfolioScientific Reports2045-23222024-10-0114111510.1038/s41598-024-76727-wModeling a biofluid-derived extracellular vesicle surface signature to differentiate pediatric idiopathic nephrotic syndrome clinical subgroupsGiulia Cricri0Andrea Gobbini1Stefania Bruno2Linda Bellucci3Sarah Tassinari4Federico Caicci5Chiara Tamburello6Teresa Nittoli7Irene Paraboschi8Alfredo Berrettini9Renata Grifantini10Benedetta Bussolati11William Morello12Giovanni Montini13Federica Collino14Laboratory of Translational Research in Paediatric Nephro-Urology, Fondazione IRCCS Ca’ Granda-Ospedale Maggiore PoliclinicoIstituto Nazionale Genetica Molecolare (INGM), Istituto Nazionale Genetica Molecolare Romeo ed Enrica InvernizziDepartment of Medical Sciences, University of TurinLaboratory of Translational Research in Paediatric Nephro-Urology, Fondazione IRCCS Ca’ Granda-Ospedale Maggiore PoliclinicoDepartment of Molecular Biotechnology and Health Sciences, University of TurinDepartment of Biology, University of PadovaPaediatric Nephrology, Dialysis and Transplant Unit, Fondazione IRCCS Ca’ Granda-Ospedale Maggiore PoliclinicoPaediatric Nephrology, Dialysis and Transplant Unit, Fondazione IRCCS Ca’ Granda-Ospedale Maggiore PoliclinicoPediatric Urology Unit, Fondazione IRCCS Ca’ Granda-Ospedale Maggiore PoliclinicoPediatric Urology Unit, Fondazione IRCCS Ca’ Granda-Ospedale Maggiore PoliclinicoIstituto Nazionale Genetica Molecolare (INGM), Istituto Nazionale Genetica Molecolare Romeo ed Enrica InvernizziDepartment of Medical Sciences, University of TurinPaediatric Nephrology, Dialysis and Transplant Unit, Fondazione IRCCS Ca’ Granda-Ospedale Maggiore PoliclinicoLaboratory of Translational Research in Paediatric Nephro-Urology, Fondazione IRCCS Ca’ Granda-Ospedale Maggiore PoliclinicoLaboratory of Translational Research in Paediatric Nephro-Urology, Fondazione IRCCS Ca’ Granda-Ospedale Maggiore PoliclinicoAbstract Idiopathic Nephrotic Syndrome (INS) is a common childhood glomerular disease requiring intense immunosuppressive drug treatments. Prediction of treatment response and the occurrence of relapses remains challenging. Biofluid-derived extracellular vesicles (EVs) may serve as novel liquid biopsies for INS classification and monitoring. Our cohort was composed of 105 INS children at different clinical time points (onset, relapse, and persistent proteinuria, remission, respectively), and 19 healthy controls. The expression of 37 surface EV surface markers was evaluated by flow cytometry in serum (n = 83) and urine (n = 74) from INS children (mean age = 10.1, 58% males) at different time points. Urine EVs (n = 7) and serum EVs (n = 11) from age-matched healthy children (mean age = 7.8, 94% males) were also analyzed. Tetraspanin expression in urine EVs was enhanced during active disease phase in respect to the remission group and positively correlates with proteinuria levels. Unsupervised clustering analysis identified an INS signature of 8 markers related to immunity and angiogenesis/adhesion processes. The CD41b, CD29, and CD105 showed the best diagnostic scores separating the INS active phase from the healthy condition. Interestingly, combining urinary and serum EV markers from the same patient improved the precision of clinical staging separation. Three urinary biomarkers (CD19, CD44, and CD8) were able to classify INS based on steroid sensitivity. Biofluid EVs offer a non-invasive tool for INS clinical subclassification and “personalized” interventions.https://doi.org/10.1038/s41598-024-76727-wIdiopathic nephrotic syndromeExtracellular vesiclesProtein biomarkersSteroid resistance |
| spellingShingle | Giulia Cricri Andrea Gobbini Stefania Bruno Linda Bellucci Sarah Tassinari Federico Caicci Chiara Tamburello Teresa Nittoli Irene Paraboschi Alfredo Berrettini Renata Grifantini Benedetta Bussolati William Morello Giovanni Montini Federica Collino Modeling a biofluid-derived extracellular vesicle surface signature to differentiate pediatric idiopathic nephrotic syndrome clinical subgroups Scientific Reports Idiopathic nephrotic syndrome Extracellular vesicles Protein biomarkers Steroid resistance |
| title | Modeling a biofluid-derived extracellular vesicle surface signature to differentiate pediatric idiopathic nephrotic syndrome clinical subgroups |
| title_full | Modeling a biofluid-derived extracellular vesicle surface signature to differentiate pediatric idiopathic nephrotic syndrome clinical subgroups |
| title_fullStr | Modeling a biofluid-derived extracellular vesicle surface signature to differentiate pediatric idiopathic nephrotic syndrome clinical subgroups |
| title_full_unstemmed | Modeling a biofluid-derived extracellular vesicle surface signature to differentiate pediatric idiopathic nephrotic syndrome clinical subgroups |
| title_short | Modeling a biofluid-derived extracellular vesicle surface signature to differentiate pediatric idiopathic nephrotic syndrome clinical subgroups |
| title_sort | modeling a biofluid derived extracellular vesicle surface signature to differentiate pediatric idiopathic nephrotic syndrome clinical subgroups |
| topic | Idiopathic nephrotic syndrome Extracellular vesicles Protein biomarkers Steroid resistance |
| url | https://doi.org/10.1038/s41598-024-76727-w |
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