A novel flow cytometry panel to identify prognostic markers for steroid-sensitive forms of idiopathic nephrotic syndrome in childhood
IntroductionThe clinical evolution of steroid-sensitive forms of pediatric idiopathic nephrotic syndrome (INS) is highly heterogeneous following the standard treatment with prednisone. To date, no prognostic marker has been identified to predict the severity of the disease course starting from the f...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1379924/full |
| _version_ | 1797230445247594496 |
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| author | Martina Riganati Federica Zotta Annalisa Candino Ester Conversano Antonio Gargiulo Marco Scarsella Anna Lo Russo Chiara Bettini Francesco Emma Francesco Emma Marina Vivarelli Marina Vivarelli Manuela Colucci |
| author_facet | Martina Riganati Federica Zotta Annalisa Candino Ester Conversano Antonio Gargiulo Marco Scarsella Anna Lo Russo Chiara Bettini Francesco Emma Francesco Emma Marina Vivarelli Marina Vivarelli Manuela Colucci |
| author_sort | Martina Riganati |
| collection | DOAJ |
| description | IntroductionThe clinical evolution of steroid-sensitive forms of pediatric idiopathic nephrotic syndrome (INS) is highly heterogeneous following the standard treatment with prednisone. To date, no prognostic marker has been identified to predict the severity of the disease course starting from the first episode.MethodsIn this monocentric prospective cohort study we set up a reproducible and standardized flow cytometry panel using two sample tubes (one for B-cell and one for T-cell subsets) to extensively characterized the lymphocyte repertoire of INS pediatric patients. A total of 44 children with INS at disease onset were enrolled, sampled before and 3 months after standard induction therapy with prednisone and followed for 12 months to correctly classify their disease based on relapses. Age-matched controls with non immune-mediated renal diseases or with urological disorders were also enrolled. Demographical, clinical, laboratory and immunosuppressive treatment data were registered.ResultsWe found that children with INS at disease onset had significantly higher circulating levels of total CD19+ and specific B-cell subsets (transitional, mature-naïve, plasmablasts/plasmacells, CD19+CD27+, unswitched, switched and atypical memory B cells) and reduced circulating levels of Tregs, when compared to age-matched controls. Prednisone therapy restored most B- and T-cell alterations. When patients were subdivided based on disease relapse, relapsing patients had significantly more transitional, CD19+CD27+ memory and in particular unswitched memory B cells at disease onset, which were predictive of a higher risk of relapse in steroid-sensitive patients by logistic regression analysis, irrespective of age. In accordance, B-cell dysregulations resulted mainly associated with steroid-dependence when patients were stratified in different disease severity forms. Of note, Treg levels were reduced independently from the disease subgroup and were not completely normalized by prednisone treatment.ConclusionWe have set up a novel, reproducible, disease-specific flow cytometry panel that allows a comprehensive characterization of circulating lymphocytes. We found that, at disease onset, relapsing patients had significantly more transitional, CD19+CD27+ memory and unswitched memory B cells and those who are at higher risk of relapse had increased circulating levels of unswitched memory B cells, independently of age. This approach can allow prediction of clinical evolution, monitoring of immunosuppression and tailored treatment in different forms of INS. |
| first_indexed | 2024-04-24T15:28:36Z |
| format | Article |
| id | doaj.art-3f3c7487c63345f08ffaa0fecd3b99c2 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-24T15:28:36Z |
| publishDate | 2024-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-3f3c7487c63345f08ffaa0fecd3b99c22024-04-02T04:56:44ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-04-011510.3389/fimmu.2024.13799241379924A novel flow cytometry panel to identify prognostic markers for steroid-sensitive forms of idiopathic nephrotic syndrome in childhoodMartina Riganati0Federica Zotta1Annalisa Candino2Ester Conversano3Antonio Gargiulo4Marco Scarsella5Anna Lo Russo6Chiara Bettini7Francesco Emma8Francesco Emma9Marina Vivarelli10Marina Vivarelli11Manuela Colucci12Laboratory of Nephrology, Bambino Gesù Children’s Hospital Scientific Institute for Research and Health Care (IRCCS), Rome, ItalyDivision of Nephrology, Bambino Gesù Children’s Hospital Scientific Institute for Research and Health Care (IRCCS), Rome, ItalyDivision of Nephrology, Bambino Gesù Children’s Hospital Scientific Institute for Research and Health Care (IRCCS), Rome, ItalyDivision of Nephrology, Bambino Gesù Children’s Hospital Scientific Institute for Research and Health Care (IRCCS), Rome, ItalyDivision of Nephrology, Bambino Gesù Children’s Hospital Scientific Institute for Research and Health Care (IRCCS), Rome, ItalyResearch Laboratories, Bambino Gesù Children’s Hospital Scientific Institute for Research and Health Care (IRCCS), Rome, ItalyResearch Laboratories, Bambino Gesù Children’s Hospital Scientific Institute for Research and Health Care (IRCCS), Rome, ItalyDivision of Nephrology, Bambino Gesù Children’s Hospital Scientific Institute for Research and Health Care (IRCCS), Rome, ItalyLaboratory of Nephrology, Bambino Gesù Children’s Hospital Scientific Institute for Research and Health Care (IRCCS), Rome, ItalyDivision of Nephrology, Bambino Gesù Children’s Hospital Scientific Institute for Research and Health Care (IRCCS), Rome, ItalyLaboratory of Nephrology, Bambino Gesù Children’s Hospital Scientific Institute for Research and Health Care (IRCCS), Rome, ItalyDivision of Nephrology, Bambino Gesù Children’s Hospital Scientific Institute for Research and Health Care (IRCCS), Rome, ItalyLaboratory of Nephrology, Bambino Gesù Children’s Hospital Scientific Institute for Research and Health Care (IRCCS), Rome, ItalyIntroductionThe clinical evolution of steroid-sensitive forms of pediatric idiopathic nephrotic syndrome (INS) is highly heterogeneous following the standard treatment with prednisone. To date, no prognostic marker has been identified to predict the severity of the disease course starting from the first episode.MethodsIn this monocentric prospective cohort study we set up a reproducible and standardized flow cytometry panel using two sample tubes (one for B-cell and one for T-cell subsets) to extensively characterized the lymphocyte repertoire of INS pediatric patients. A total of 44 children with INS at disease onset were enrolled, sampled before and 3 months after standard induction therapy with prednisone and followed for 12 months to correctly classify their disease based on relapses. Age-matched controls with non immune-mediated renal diseases or with urological disorders were also enrolled. Demographical, clinical, laboratory and immunosuppressive treatment data were registered.ResultsWe found that children with INS at disease onset had significantly higher circulating levels of total CD19+ and specific B-cell subsets (transitional, mature-naïve, plasmablasts/plasmacells, CD19+CD27+, unswitched, switched and atypical memory B cells) and reduced circulating levels of Tregs, when compared to age-matched controls. Prednisone therapy restored most B- and T-cell alterations. When patients were subdivided based on disease relapse, relapsing patients had significantly more transitional, CD19+CD27+ memory and in particular unswitched memory B cells at disease onset, which were predictive of a higher risk of relapse in steroid-sensitive patients by logistic regression analysis, irrespective of age. In accordance, B-cell dysregulations resulted mainly associated with steroid-dependence when patients were stratified in different disease severity forms. Of note, Treg levels were reduced independently from the disease subgroup and were not completely normalized by prednisone treatment.ConclusionWe have set up a novel, reproducible, disease-specific flow cytometry panel that allows a comprehensive characterization of circulating lymphocytes. We found that, at disease onset, relapsing patients had significantly more transitional, CD19+CD27+ memory and unswitched memory B cells and those who are at higher risk of relapse had increased circulating levels of unswitched memory B cells, independently of age. This approach can allow prediction of clinical evolution, monitoring of immunosuppression and tailored treatment in different forms of INS.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1379924/fullidiopathic nephrotic syndromeB cellT celllymphocyte profileprognostic markers |
| spellingShingle | Martina Riganati Federica Zotta Annalisa Candino Ester Conversano Antonio Gargiulo Marco Scarsella Anna Lo Russo Chiara Bettini Francesco Emma Francesco Emma Marina Vivarelli Marina Vivarelli Manuela Colucci A novel flow cytometry panel to identify prognostic markers for steroid-sensitive forms of idiopathic nephrotic syndrome in childhood Frontiers in Immunology idiopathic nephrotic syndrome B cell T cell lymphocyte profile prognostic markers |
| title | A novel flow cytometry panel to identify prognostic markers for steroid-sensitive forms of idiopathic nephrotic syndrome in childhood |
| title_full | A novel flow cytometry panel to identify prognostic markers for steroid-sensitive forms of idiopathic nephrotic syndrome in childhood |
| title_fullStr | A novel flow cytometry panel to identify prognostic markers for steroid-sensitive forms of idiopathic nephrotic syndrome in childhood |
| title_full_unstemmed | A novel flow cytometry panel to identify prognostic markers for steroid-sensitive forms of idiopathic nephrotic syndrome in childhood |
| title_short | A novel flow cytometry panel to identify prognostic markers for steroid-sensitive forms of idiopathic nephrotic syndrome in childhood |
| title_sort | novel flow cytometry panel to identify prognostic markers for steroid sensitive forms of idiopathic nephrotic syndrome in childhood |
| topic | idiopathic nephrotic syndrome B cell T cell lymphocyte profile prognostic markers |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1379924/full |
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