Multidimensional inflammatory and immunological endotypes of idiopathic focal segmental glomerulosclerosis and their association with treatment outcomes

Objectives. Idiopathic focal segmental glomerulosclerosis (FSGS) has been linked to immunological and inflammatory response dysregulations. The aim of this study was to find endotypes of FSGS patients using a cluster (CL) analysis based on inflammatory and immunological variables, and to analyse whe...

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Autores: Roca, Neus|||0000-0002-7129-5438, Madrid, Alvaro, Lopez, Mercedes, Fraga Rodriguez, Gloria Maria|||0000-0002-7682-1396, Jatem, Elias, Gonzalez, Jorge, Martínez, Cristina|||0000-0002-9368-1356, Segarra, Alfons
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:271905
Acceso en línea:https://ddd.uab.cat/record/271905
https://dx.doi.org/urn:doi:10.1093/ckj/sfaa265
Access Level:acceso abierto
Palabra clave:Cluster analysis
Endotypes
Focal segmental glomerulosclerosis
Idiopathic nephrotic syndrome
Inflammatory response
Interleukins
Lymphocyte populations
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spelling Multidimensional inflammatory and immunological endotypes of idiopathic focal segmental glomerulosclerosis and their association with treatment outcomesRoca, Neus|||0000-0002-7129-5438Madrid, AlvaroLopez, MercedesFraga Rodriguez, Gloria Maria|||0000-0002-7682-1396Jatem, EliasGonzalez, JorgeMartínez, Cristina|||0000-0002-9368-1356Segarra, AlfonsCluster analysisEndotypesFocal segmental glomerulosclerosisIdiopathic nephrotic syndromeInflammatory responseInterleukinsLymphocyte populationsObjectives. Idiopathic focal segmental glomerulosclerosis (FSGS) has been linked to immunological and inflammatory response dysregulations. The aim of this study was to find endotypes of FSGS patients using a cluster (CL) analysis based on inflammatory and immunological variables, and to analyse whether a certain endotype is associated with response to treatment with corticosteroids. Methods. This prospective observational study included patients with idiopathic FSGS diagnosed by kidney biopsy. Serum levels of soluble interleukin (IL)-1 receptor, tumoural necrosis factor alpha, Interferon gamma (IFNc), IL-6, IL-17, IL-12, IL-23, IL-13, IL-4, IL-5, IL-6, haemopexin (Hx), haptoglobin (Hgl), soluble urokinase-type plasminogen activator receptor (suPAR) and urinary CD80 (uCD80) were measured with enzyme-linked immunosorbent assay or nephelometry. T-helper lymphocyte populations and T-regulatory lymphocytes were analysed by flow cytometry. A factorial analysis followed by a k-means CL analysis was performed. Results. A total of 79 FSGS patients were included. Three CLs were identified. CL1 (27.8%) included IL-12, IL-17, IL-23 and a T helper 17 (Th17) pattern. CL2 (20.2%) included IL-4, IL-5, IL-13, immunoglobulin E and Th2 pattern. CL3 (51.8%) included IL-6, Hx, Hgl, suPAR and uCD80. There were no differences in age, gender, kidney function, albumin or proteinuria among CLs. About 42/79 patients (53.1%) showed cortico-resistance. The prevalence of cortico-resistance was significantly lower in CL2 (4/16, 25%) than in CL1 (16/26, 72.7%) and CL3 (22/41, 53.7%) (P = 0.018), with no significant differences between CLs 1 and 3 (P = 0.14). Conclusions. Patients with FSGS and indistinguishable clinical presentation at diagnosis were classified in three distinct CLs according to predominant Th17, Th2 and acute inflammatory responses that display differences in clinical response to treatment with corticosteroids. 22021-01-0120212021-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/271905https://dx.doi.org/urn:doi:10.1093/ckj/sfaa265reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by-nc/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2719052026-06-06T12:50:31Z
dc.title.none.fl_str_mv Multidimensional inflammatory and immunological endotypes of idiopathic focal segmental glomerulosclerosis and their association with treatment outcomes
title Multidimensional inflammatory and immunological endotypes of idiopathic focal segmental glomerulosclerosis and their association with treatment outcomes
spellingShingle Multidimensional inflammatory and immunological endotypes of idiopathic focal segmental glomerulosclerosis and their association with treatment outcomes
Roca, Neus|||0000-0002-7129-5438
Cluster analysis
Endotypes
Focal segmental glomerulosclerosis
Idiopathic nephrotic syndrome
Inflammatory response
Interleukins
Lymphocyte populations
title_short Multidimensional inflammatory and immunological endotypes of idiopathic focal segmental glomerulosclerosis and their association with treatment outcomes
title_full Multidimensional inflammatory and immunological endotypes of idiopathic focal segmental glomerulosclerosis and their association with treatment outcomes
title_fullStr Multidimensional inflammatory and immunological endotypes of idiopathic focal segmental glomerulosclerosis and their association with treatment outcomes
title_full_unstemmed Multidimensional inflammatory and immunological endotypes of idiopathic focal segmental glomerulosclerosis and their association with treatment outcomes
title_sort Multidimensional inflammatory and immunological endotypes of idiopathic focal segmental glomerulosclerosis and their association with treatment outcomes
dc.creator.none.fl_str_mv Roca, Neus|||0000-0002-7129-5438
Madrid, Alvaro
Lopez, Mercedes
Fraga Rodriguez, Gloria Maria|||0000-0002-7682-1396
Jatem, Elias
Gonzalez, Jorge
Martínez, Cristina|||0000-0002-9368-1356
Segarra, Alfons
author Roca, Neus|||0000-0002-7129-5438
author_facet Roca, Neus|||0000-0002-7129-5438
Madrid, Alvaro
Lopez, Mercedes
Fraga Rodriguez, Gloria Maria|||0000-0002-7682-1396
Jatem, Elias
Gonzalez, Jorge
Martínez, Cristina|||0000-0002-9368-1356
Segarra, Alfons
author_role author
author2 Madrid, Alvaro
Lopez, Mercedes
Fraga Rodriguez, Gloria Maria|||0000-0002-7682-1396
Jatem, Elias
Gonzalez, Jorge
Martínez, Cristina|||0000-0002-9368-1356
Segarra, Alfons
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Cluster analysis
Endotypes
Focal segmental glomerulosclerosis
Idiopathic nephrotic syndrome
Inflammatory response
Interleukins
Lymphocyte populations
topic Cluster analysis
Endotypes
Focal segmental glomerulosclerosis
Idiopathic nephrotic syndrome
Inflammatory response
Interleukins
Lymphocyte populations
description Objectives. Idiopathic focal segmental glomerulosclerosis (FSGS) has been linked to immunological and inflammatory response dysregulations. The aim of this study was to find endotypes of FSGS patients using a cluster (CL) analysis based on inflammatory and immunological variables, and to analyse whether a certain endotype is associated with response to treatment with corticosteroids. Methods. This prospective observational study included patients with idiopathic FSGS diagnosed by kidney biopsy. Serum levels of soluble interleukin (IL)-1 receptor, tumoural necrosis factor alpha, Interferon gamma (IFNc), IL-6, IL-17, IL-12, IL-23, IL-13, IL-4, IL-5, IL-6, haemopexin (Hx), haptoglobin (Hgl), soluble urokinase-type plasminogen activator receptor (suPAR) and urinary CD80 (uCD80) were measured with enzyme-linked immunosorbent assay or nephelometry. T-helper lymphocyte populations and T-regulatory lymphocytes were analysed by flow cytometry. A factorial analysis followed by a k-means CL analysis was performed. Results. A total of 79 FSGS patients were included. Three CLs were identified. CL1 (27.8%) included IL-12, IL-17, IL-23 and a T helper 17 (Th17) pattern. CL2 (20.2%) included IL-4, IL-5, IL-13, immunoglobulin E and Th2 pattern. CL3 (51.8%) included IL-6, Hx, Hgl, suPAR and uCD80. There were no differences in age, gender, kidney function, albumin or proteinuria among CLs. About 42/79 patients (53.1%) showed cortico-resistance. The prevalence of cortico-resistance was significantly lower in CL2 (4/16, 25%) than in CL1 (16/26, 72.7%) and CL3 (22/41, 53.7%) (P = 0.018), with no significant differences between CLs 1 and 3 (P = 0.14). Conclusions. Patients with FSGS and indistinguishable clinical presentation at diagnosis were classified in three distinct CLs according to predominant Th17, Th2 and acute inflammatory responses that display differences in clinical response to treatment with corticosteroids.
publishDate 2021
dc.date.none.fl_str_mv 2
2021-01-01
2021
2021-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/271905
https://dx.doi.org/urn:doi:10.1093/ckj/sfaa265
url https://ddd.uab.cat/record/271905
https://dx.doi.org/urn:doi:10.1093/ckj/sfaa265
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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