Immunological biomarkers associated with survival in a cohort of Argentinian patients with common variable immunodeficiency

Autores
Kahn, Adrian Mario; Luque, Gabriela; Cuestas, Eduardo; Basquiera, Ana Lisa; Ricchi, Brenda; Schmitz Abe, Klaus; Charbonnier, Louis Marie; Benamar, Mehdi; Motrich, Ruben Dario; Chatila, Talal A.; Rivero, Virginia Elena
Año de publicación
2024
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: Common Variable Immunodeficiency (CVID) is the most common symptomatic syndrome among inborn errors of immunity (IEI). Although several aspects of CVID immunopathology have been elucidated, predictive factors for mortality are incompletely defined. A genetic cause can only be identified in approximately 30% of patients. Objectives: To develop a mortality predictive score based on the immunophenotypes and genotypes of CVID patients. Methods: Twenty-one patients diagnosed with CVID in Cordoba, Argentina, were analyzed for clinical and laboratory data. Immunophenotyping was done by flow cytometry. CVID-associated mutations were identified by whole exome sequencing (WES). Results: Live (15) and deceased (6) patients were compared. Univariate analysis showed significant differences in CD4+ T cells (p=0.002), Natural Killer (NK) cells (p=0.001) and memory switched B cells (p=0.001) between groups. Logistic regression analysis showed a negative correlation between CD4, NK and memory switched B cells counts and probability of survival over a 10-year period [CD4+ T cells: OR 1.01 (95% CI: 1.001- 1,020); NK cells: OR 1.07 (95% CI:1.02-1.17) and memory switched B cells: OR 26.23 (95% CI: 2.06-2651.96). ROC curve analysis identified a survival cut off point for each parameter: CD4+ T cells 546 cell/ml AUC 0.87 (sensitivity 60%-specificity 100%), memory switched B cells 0.84 cells/ml AUC 0.92 (sensitivity 100%-specificity 85%), NK cells 45 cells/ml for AUC 0.92 (sensitivity 83%-specificity 100%), %). Genetic analysis on 14 patients from the cohort (9 females, 5 males) revealed mutations associated with IEI in 6 patients. Conclusions: A score to predict mortality is proposed based on CD4, NK and memory switched B cell number in patients with CVID.
Fil: Kahn, Adrian Mario. Hospital Privado Universitario de Cordoba.; Argentina. Instituto Universitario de Ciencias Biomédicas de Córdoba; Argentina. Centro de Inmunologia Clinica de Cordoba; Argentina
Fil: Luque, Gabriela. Hospital Privado Universitario de Cordoba.; Argentina
Fil: Cuestas, Eduardo. Hospital Privado Universitario de Cordoba.; Argentina. Instituto Universitario de Ciencias Biomédicas de Córdoba; Argentina
Fil: Basquiera, Ana Lisa. Hospital Privado Universitario de Cordoba.; Argentina. Instituto Universitario de Ciencias Biomédicas de Córdoba; Argentina
Fil: Ricchi, Brenda. Hospital Privado Universitario de Cordoba.; Argentina
Fil: Schmitz Abe, Klaus. Boston Childrens Hospital; Estados Unidos. Harvard Medical School; Estados Unidos. Jackson Health System; Estados Unidos
Fil: Charbonnier, Louis Marie. Boston Childrens Hospital; Estados Unidos. Harvard Medical School; Estados Unidos
Fil: Benamar, Mehdi. Boston Childrens Hospital; Estados Unidos. Harvard Medical School; Estados Unidos
Fil: Motrich, Ruben Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina. Centro de Inmunologia Clinica de Cordoba; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentina
Fil: Chatila, Talal A.. Boston Childrens Hospital; Estados Unidos. Harvard Medical School; Estados Unidos
Fil: Rivero, Virginia Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina. Centro de Inmunologia Clinica de Cordoba; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentina
Materia
CVID
Score
Mortality
Outcomes
WES
B cells subpopulations
T cells
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/266843
Acceder
id CONICETDig_23a16eb27d64980aaf8473e79b745729
oai_identifier_str oai:ri.conicet.gov.ar:11336/266843
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Immunological biomarkers associated with survival in a cohort of Argentinian patients with common variable immunodeficiencyKahn, Adrian MarioLuque, GabrielaCuestas, EduardoBasquiera, Ana LisaRicchi, BrendaSchmitz Abe, KlausCharbonnier, Louis MarieBenamar, MehdiMotrich, Ruben DarioChatila, Talal A.Rivero, Virginia ElenaCVIDScoreMortalityOutcomesWESB cells subpopulationsT cellshttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Background: Common Variable Immunodeficiency (CVID) is the most common symptomatic syndrome among inborn errors of immunity (IEI). Although several aspects of CVID immunopathology have been elucidated, predictive factors for mortality are incompletely defined. A genetic cause can only be identified in approximately 30% of patients. Objectives: To develop a mortality predictive score based on the immunophenotypes and genotypes of CVID patients. Methods: Twenty-one patients diagnosed with CVID in Cordoba, Argentina, were analyzed for clinical and laboratory data. Immunophenotyping was done by flow cytometry. CVID-associated mutations were identified by whole exome sequencing (WES). Results: Live (15) and deceased (6) patients were compared. Univariate analysis showed significant differences in CD4+ T cells (p=0.002), Natural Killer (NK) cells (p=0.001) and memory switched B cells (p=0.001) between groups. Logistic regression analysis showed a negative correlation between CD4, NK and memory switched B cells counts and probability of survival over a 10-year period [CD4+ T cells: OR 1.01 (95% CI: 1.001- 1,020); NK cells: OR 1.07 (95% CI:1.02-1.17) and memory switched B cells: OR 26.23 (95% CI: 2.06-2651.96). ROC curve analysis identified a survival cut off point for each parameter: CD4+ T cells 546 cell/ml AUC 0.87 (sensitivity 60%-specificity 100%), memory switched B cells 0.84 cells/ml AUC 0.92 (sensitivity 100%-specificity 85%), NK cells 45 cells/ml for AUC 0.92 (sensitivity 83%-specificity 100%), %). Genetic analysis on 14 patients from the cohort (9 females, 5 males) revealed mutations associated with IEI in 6 patients. Conclusions: A score to predict mortality is proposed based on CD4, NK and memory switched B cell number in patients with CVID.Fil: Kahn, Adrian Mario. Hospital Privado Universitario de Cordoba.; Argentina. Instituto Universitario de Ciencias Biomédicas de Córdoba; Argentina. Centro de Inmunologia Clinica de Cordoba; ArgentinaFil: Luque, Gabriela. Hospital Privado Universitario de Cordoba.; ArgentinaFil: Cuestas, Eduardo. Hospital Privado Universitario de Cordoba.; Argentina. Instituto Universitario de Ciencias Biomédicas de Córdoba; ArgentinaFil: Basquiera, Ana Lisa. Hospital Privado Universitario de Cordoba.; Argentina. Instituto Universitario de Ciencias Biomédicas de Córdoba; ArgentinaFil: Ricchi, Brenda. Hospital Privado Universitario de Cordoba.; ArgentinaFil: Schmitz Abe, Klaus. Boston Childrens Hospital; Estados Unidos. Harvard Medical School; Estados Unidos. Jackson Health System; Estados UnidosFil: Charbonnier, Louis Marie. Boston Childrens Hospital; Estados Unidos. Harvard Medical School; Estados UnidosFil: Benamar, Mehdi. Boston Childrens Hospital; Estados Unidos. Harvard Medical School; Estados UnidosFil: Motrich, Ruben Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina. Centro de Inmunologia Clinica de Cordoba; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; ArgentinaFil: Chatila, Talal A.. Boston Childrens Hospital; Estados Unidos. Harvard Medical School; Estados UnidosFil: Rivero, Virginia Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina. Centro de Inmunologia Clinica de Cordoba; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; ArgentinaElsevier2024-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/266843Kahn, Adrian Mario; Luque, Gabriela; Cuestas, Eduardo; Basquiera, Ana Lisa; Ricchi, Brenda; et al.; Immunological biomarkers associated with survival in a cohort of Argentinian patients with common variable immunodeficiency; Elsevier; Journal of Allergy and Clinical Immunology: Global; 3; 4; 11-2024; 1-362772-8293CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S2772829324001073info:eu-repo/semantics/altIdentifier/doi/10.1016/j.jacig.2024.100311info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:02:15Zoai:ri.conicet.gov.ar:11336/266843instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 15:02:16.208CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Immunological biomarkers associated with survival in a cohort of Argentinian patients with common variable immunodeficiency
title Immunological biomarkers associated with survival in a cohort of Argentinian patients with common variable immunodeficiency
spellingShingle Immunological biomarkers associated with survival in a cohort of Argentinian patients with common variable immunodeficiency
Kahn, Adrian Mario
CVID
Score
Mortality
Outcomes
WES
B cells subpopulations
T cells
title_short Immunological biomarkers associated with survival in a cohort of Argentinian patients with common variable immunodeficiency
title_full Immunological biomarkers associated with survival in a cohort of Argentinian patients with common variable immunodeficiency
title_fullStr Immunological biomarkers associated with survival in a cohort of Argentinian patients with common variable immunodeficiency
title_full_unstemmed Immunological biomarkers associated with survival in a cohort of Argentinian patients with common variable immunodeficiency
title_sort Immunological biomarkers associated with survival in a cohort of Argentinian patients with common variable immunodeficiency
dc.creator.none.fl_str_mv Kahn, Adrian Mario
Luque, Gabriela
Cuestas, Eduardo
Basquiera, Ana Lisa
Ricchi, Brenda
Schmitz Abe, Klaus
Charbonnier, Louis Marie
Benamar, Mehdi
Motrich, Ruben Dario
Chatila, Talal A.
Rivero, Virginia Elena
author Kahn, Adrian Mario
author_facet Kahn, Adrian Mario
Luque, Gabriela
Cuestas, Eduardo
Basquiera, Ana Lisa
Ricchi, Brenda
Schmitz Abe, Klaus
Charbonnier, Louis Marie
Benamar, Mehdi
Motrich, Ruben Dario
Chatila, Talal A.
Rivero, Virginia Elena
author_role author
author2 Luque, Gabriela
Cuestas, Eduardo
Basquiera, Ana Lisa
Ricchi, Brenda
Schmitz Abe, Klaus
Charbonnier, Louis Marie
Benamar, Mehdi
Motrich, Ruben Dario
Chatila, Talal A.
Rivero, Virginia Elena
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv CVID
Score
Mortality
Outcomes
WES
B cells subpopulations
T cells
topic CVID
Score
Mortality
Outcomes
WES
B cells subpopulations
T cells
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Background: Common Variable Immunodeficiency (CVID) is the most common symptomatic syndrome among inborn errors of immunity (IEI). Although several aspects of CVID immunopathology have been elucidated, predictive factors for mortality are incompletely defined. A genetic cause can only be identified in approximately 30% of patients. Objectives: To develop a mortality predictive score based on the immunophenotypes and genotypes of CVID patients. Methods: Twenty-one patients diagnosed with CVID in Cordoba, Argentina, were analyzed for clinical and laboratory data. Immunophenotyping was done by flow cytometry. CVID-associated mutations were identified by whole exome sequencing (WES). Results: Live (15) and deceased (6) patients were compared. Univariate analysis showed significant differences in CD4+ T cells (p=0.002), Natural Killer (NK) cells (p=0.001) and memory switched B cells (p=0.001) between groups. Logistic regression analysis showed a negative correlation between CD4, NK and memory switched B cells counts and probability of survival over a 10-year period [CD4+ T cells: OR 1.01 (95% CI: 1.001- 1,020); NK cells: OR 1.07 (95% CI:1.02-1.17) and memory switched B cells: OR 26.23 (95% CI: 2.06-2651.96). ROC curve analysis identified a survival cut off point for each parameter: CD4+ T cells 546 cell/ml AUC 0.87 (sensitivity 60%-specificity 100%), memory switched B cells 0.84 cells/ml AUC 0.92 (sensitivity 100%-specificity 85%), NK cells 45 cells/ml for AUC 0.92 (sensitivity 83%-specificity 100%), %). Genetic analysis on 14 patients from the cohort (9 females, 5 males) revealed mutations associated with IEI in 6 patients. Conclusions: A score to predict mortality is proposed based on CD4, NK and memory switched B cell number in patients with CVID.
Fil: Kahn, Adrian Mario. Hospital Privado Universitario de Cordoba.; Argentina. Instituto Universitario de Ciencias Biomédicas de Córdoba; Argentina. Centro de Inmunologia Clinica de Cordoba; Argentina
Fil: Luque, Gabriela. Hospital Privado Universitario de Cordoba.; Argentina
Fil: Cuestas, Eduardo. Hospital Privado Universitario de Cordoba.; Argentina. Instituto Universitario de Ciencias Biomédicas de Córdoba; Argentina
Fil: Basquiera, Ana Lisa. Hospital Privado Universitario de Cordoba.; Argentina. Instituto Universitario de Ciencias Biomédicas de Córdoba; Argentina
Fil: Ricchi, Brenda. Hospital Privado Universitario de Cordoba.; Argentina
Fil: Schmitz Abe, Klaus. Boston Childrens Hospital; Estados Unidos. Harvard Medical School; Estados Unidos. Jackson Health System; Estados Unidos
Fil: Charbonnier, Louis Marie. Boston Childrens Hospital; Estados Unidos. Harvard Medical School; Estados Unidos
Fil: Benamar, Mehdi. Boston Childrens Hospital; Estados Unidos. Harvard Medical School; Estados Unidos
Fil: Motrich, Ruben Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina. Centro de Inmunologia Clinica de Cordoba; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentina
Fil: Chatila, Talal A.. Boston Childrens Hospital; Estados Unidos. Harvard Medical School; Estados Unidos
Fil: Rivero, Virginia Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina. Centro de Inmunologia Clinica de Cordoba; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentina
description Background: Common Variable Immunodeficiency (CVID) is the most common symptomatic syndrome among inborn errors of immunity (IEI). Although several aspects of CVID immunopathology have been elucidated, predictive factors for mortality are incompletely defined. A genetic cause can only be identified in approximately 30% of patients. Objectives: To develop a mortality predictive score based on the immunophenotypes and genotypes of CVID patients. Methods: Twenty-one patients diagnosed with CVID in Cordoba, Argentina, were analyzed for clinical and laboratory data. Immunophenotyping was done by flow cytometry. CVID-associated mutations were identified by whole exome sequencing (WES). Results: Live (15) and deceased (6) patients were compared. Univariate analysis showed significant differences in CD4+ T cells (p=0.002), Natural Killer (NK) cells (p=0.001) and memory switched B cells (p=0.001) between groups. Logistic regression analysis showed a negative correlation between CD4, NK and memory switched B cells counts and probability of survival over a 10-year period [CD4+ T cells: OR 1.01 (95% CI: 1.001- 1,020); NK cells: OR 1.07 (95% CI:1.02-1.17) and memory switched B cells: OR 26.23 (95% CI: 2.06-2651.96). ROC curve analysis identified a survival cut off point for each parameter: CD4+ T cells 546 cell/ml AUC 0.87 (sensitivity 60%-specificity 100%), memory switched B cells 0.84 cells/ml AUC 0.92 (sensitivity 100%-specificity 85%), NK cells 45 cells/ml for AUC 0.92 (sensitivity 83%-specificity 100%), %). Genetic analysis on 14 patients from the cohort (9 females, 5 males) revealed mutations associated with IEI in 6 patients. Conclusions: A score to predict mortality is proposed based on CD4, NK and memory switched B cell number in patients with CVID.
publishDate 2024
dc.date.none.fl_str_mv 2024-11
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/266843
Kahn, Adrian Mario; Luque, Gabriela; Cuestas, Eduardo; Basquiera, Ana Lisa; Ricchi, Brenda; et al.; Immunological biomarkers associated with survival in a cohort of Argentinian patients with common variable immunodeficiency; Elsevier; Journal of Allergy and Clinical Immunology: Global; 3; 4; 11-2024; 1-36
2772-8293
CONICET Digital
CONICET
url http://hdl.handle.net/11336/266843
identifier_str_mv Kahn, Adrian Mario; Luque, Gabriela; Cuestas, Eduardo; Basquiera, Ana Lisa; Ricchi, Brenda; et al.; Immunological biomarkers associated with survival in a cohort of Argentinian patients with common variable immunodeficiency; Elsevier; Journal of Allergy and Clinical Immunology: Global; 3; 4; 11-2024; 1-36
2772-8293
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S2772829324001073
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.jacig.2024.100311
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.22299

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