Immunological biomarkers associated with survival in a cohort of Argentinian patients with common variable immunodeficiency
Background: Common variable immunodeficiency (CVID) is the most common symptomatic syndrome among inborn errors of immunity. Although several aspects of CVID immunopathology have been elucidated, predictive factors for mortality are incompletely defined. A genetic cause can be identified only in app...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-11-01
|
| Series: | Journal of Allergy and Clinical Immunology: Global |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772829324001073 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1846169372251389952 |
|---|---|
| author | Adrian Kahn, MD, PhD Gabriela Luque, BSc Eduardo Cuestas, MD, PhD Ana Basquiera, MD, PhD Brenda Ricchi, BSc Klaus Schmitz-Abe, PhD Louis-Marie Charbonnier, MD Mehdi Benamar, PhD Ruben Dario Motrich, PhD Talal A. Chatila, MD, PhD Virginia E. Rivero, PhD |
| author_facet | Adrian Kahn, MD, PhD Gabriela Luque, BSc Eduardo Cuestas, MD, PhD Ana Basquiera, MD, PhD Brenda Ricchi, BSc Klaus Schmitz-Abe, PhD Louis-Marie Charbonnier, MD Mehdi Benamar, PhD Ruben Dario Motrich, PhD Talal A. Chatila, MD, PhD Virginia E. Rivero, PhD |
| author_sort | Adrian Kahn, MD, PhD |
| collection | DOAJ |
| description | Background: Common variable immunodeficiency (CVID) is the most common symptomatic syndrome among inborn errors of immunity. Although several aspects of CVID immunopathology have been elucidated, predictive factors for mortality are incompletely defined. A genetic cause can be identified only in approximately 30% of patients. Objective: We sought to develop a mortality predictive score on the basis of the immunophenotypes and genotypes of patients with CVID. Methods: Twenty-one patients diagnosed with CVID in Córdoba, Argentina, were analyzed for clinical and laboratory data. Immunophenotyping was done by flow cytometry. CVID-associated mutations were identified by whole-exome sequencing. Results: Alive (15) and deceased (6) patients were compared. Univariate analysis showed significant differences in CD4+ T cells (P = .002), natural killer (NK) cells (P = .001), and memory switched B cells (P = .001) between groups. Logistic regression analysis showed a negative correlation between CD4+, NK, and memory switched B-cell counts and probability of survival over a 10-year period (CD4+ T cells: odds ratio [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). Receiver-operating characteristic curve analysis identified a survival cutoff point for each parameter (CD4+ T cells: 546 cells/mL; AUC, 0.87; sensitivity, 60%; specificity, 100%; memory switched B cells: 0.84 cells/mL; AUC, 0.92; sensitivity, 100%; specificity, 85%; and NK cells: 45 cells/mL; AUC, 0.92; sensitivity, 83%; specificity, 100%). Genetic analysis on 14 (9 female and 5 male) patients from the cohort revealed mutations associated with inborn errors of immunity in 6 patients. Conclusions: A score to predict mortality is proposed on the basis of CD4+ T, NK, and memory switched B-cell counts in patients with CVID. |
| format | Article |
| id | doaj-art-da6e33b9adc54019b9431935a91780cc |
| institution | Kabale University |
| issn | 2772-8293 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Allergy and Clinical Immunology: Global |
| spelling | doaj-art-da6e33b9adc54019b9431935a91780cc2024-11-13T04:30:44ZengElsevierJournal of Allergy and Clinical Immunology: Global2772-82932024-11-0134100311Immunological biomarkers associated with survival in a cohort of Argentinian patients with common variable immunodeficiencyAdrian Kahn, MD, PhD0Gabriela Luque, BSc1Eduardo Cuestas, MD, PhD2Ana Basquiera, MD, PhD3Brenda Ricchi, BSc4Klaus Schmitz-Abe, PhD5Louis-Marie Charbonnier, MD6Mehdi Benamar, PhD7Ruben Dario Motrich, PhD8Talal A. Chatila, MD, PhD9Virginia E. Rivero, PhD10Servicio de Alergia e Inmunología Clínica, Hospital Privado Universitario de Córdoba, Córdoba, Argentina; Instituto Universitario de Ciencias Biomédicas de Córdoba, Córdoba, Argentina; FOCIS Center of Excellence Centro de Inmunologia Clinica de Cordoba (CICC), Córdoba, Argentina; Corresponding author: Adrian Kahn, MD, PhD, Av Naciones Unidas 346, Parque Velez Sarsfielf, Cordoba 5010, Argentina. Or: Virginia E. Rivero, PhD, Haya de la Torre y Medina Allende, Ciudad Universitaria, Cordoba 5000, Argentina.Servicio de Oncohematologia, Hospital Privado Universitario de Córdoba, Córdoba, ArgentinaInstituto Universitario de Ciencias Biomédicas de Córdoba, Córdoba, Argentina; Servicio de Pediatria, Hospital Privado Universitario de Córdoba, Córdoba, ArgentinaInstituto Universitario de Ciencias Biomédicas de Córdoba, Córdoba, Argentina; Servicio de Oncohematologia, Hospital Privado Universitario de Córdoba, Córdoba, ArgentinaServicio de Oncohematologia, Hospital Privado Universitario de Córdoba, Córdoba, ArgentinaDivision of Immunology, Boston Children’s Hospital, Boston, Mass; Department of Pediatrics, Harvard Medical School, Boston, Mass; Manton Center for Orphan Disease Research, Boston Children’s Hospital, Boston, Mass; Division of Neonatology, Department of Pediatrics, University of Miami Miller School of Medicine and Holtz Children’s Hospital, Jackson Health System, Miami, FlaDivision of Immunology, Boston Children’s Hospital, Boston, Mass; Department of Pediatrics, Harvard Medical School, Boston, MassDivision of Immunology, Boston Children’s Hospital, Boston, Mass; Department of Pediatrics, Harvard Medical School, Boston, MassFOCIS Center of Excellence Centro de Inmunologia Clinica de Cordoba (CICC), Córdoba, Argentina; Centro de Investigaciones en Bioquímica Clínica e Inmunología, CIBICI-CONICET, Córdoba, Argentina; Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, ArgentinaDivision of Immunology, Boston Children’s Hospital, Boston, Mass; Department of Pediatrics, Harvard Medical School, Boston, MassFOCIS Center of Excellence Centro de Inmunologia Clinica de Cordoba (CICC), Córdoba, Argentina; Centro de Investigaciones en Bioquímica Clínica e Inmunología, CIBICI-CONICET, Córdoba, Argentina; Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina; Corresponding author: Adrian Kahn, MD, PhD, Av Naciones Unidas 346, Parque Velez Sarsfielf, Cordoba 5010, Argentina. Or: Virginia E. Rivero, PhD, Haya de la Torre y Medina Allende, Ciudad Universitaria, Cordoba 5000, Argentina.Background: Common variable immunodeficiency (CVID) is the most common symptomatic syndrome among inborn errors of immunity. Although several aspects of CVID immunopathology have been elucidated, predictive factors for mortality are incompletely defined. A genetic cause can be identified only in approximately 30% of patients. Objective: We sought to develop a mortality predictive score on the basis of the immunophenotypes and genotypes of patients with CVID. Methods: Twenty-one patients diagnosed with CVID in Córdoba, Argentina, were analyzed for clinical and laboratory data. Immunophenotyping was done by flow cytometry. CVID-associated mutations were identified by whole-exome sequencing. Results: Alive (15) and deceased (6) patients were compared. Univariate analysis showed significant differences in CD4+ T cells (P = .002), natural killer (NK) cells (P = .001), and memory switched B cells (P = .001) between groups. Logistic regression analysis showed a negative correlation between CD4+, NK, and memory switched B-cell counts and probability of survival over a 10-year period (CD4+ T cells: odds ratio [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). Receiver-operating characteristic curve analysis identified a survival cutoff point for each parameter (CD4+ T cells: 546 cells/mL; AUC, 0.87; sensitivity, 60%; specificity, 100%; memory switched B cells: 0.84 cells/mL; AUC, 0.92; sensitivity, 100%; specificity, 85%; and NK cells: 45 cells/mL; AUC, 0.92; sensitivity, 83%; specificity, 100%). Genetic analysis on 14 (9 female and 5 male) patients from the cohort revealed mutations associated with inborn errors of immunity in 6 patients. Conclusions: A score to predict mortality is proposed on the basis of CD4+ T, NK, and memory switched B-cell counts in patients with CVID.http://www.sciencedirect.com/science/article/pii/S2772829324001073CVIDscoremortalityoutcomesWESB-cell subpopulations |
| spellingShingle | Adrian Kahn, MD, PhD Gabriela Luque, BSc Eduardo Cuestas, MD, PhD Ana Basquiera, MD, PhD Brenda Ricchi, BSc Klaus Schmitz-Abe, PhD Louis-Marie Charbonnier, MD Mehdi Benamar, PhD Ruben Dario Motrich, PhD Talal A. Chatila, MD, PhD Virginia E. Rivero, PhD Immunological biomarkers associated with survival in a cohort of Argentinian patients with common variable immunodeficiency Journal of Allergy and Clinical Immunology: Global CVID score mortality outcomes WES B-cell subpopulations |
| title | 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_short | 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 |
| topic | CVID score mortality outcomes WES B-cell subpopulations |
| url | http://www.sciencedirect.com/science/article/pii/S2772829324001073 |
| work_keys_str_mv | AT adriankahnmdphd immunologicalbiomarkersassociatedwithsurvivalinacohortofargentinianpatientswithcommonvariableimmunodeficiency AT gabrielaluquebsc immunologicalbiomarkersassociatedwithsurvivalinacohortofargentinianpatientswithcommonvariableimmunodeficiency AT eduardocuestasmdphd immunologicalbiomarkersassociatedwithsurvivalinacohortofargentinianpatientswithcommonvariableimmunodeficiency AT anabasquieramdphd immunologicalbiomarkersassociatedwithsurvivalinacohortofargentinianpatientswithcommonvariableimmunodeficiency AT brendaricchibsc immunologicalbiomarkersassociatedwithsurvivalinacohortofargentinianpatientswithcommonvariableimmunodeficiency AT klausschmitzabephd immunologicalbiomarkersassociatedwithsurvivalinacohortofargentinianpatientswithcommonvariableimmunodeficiency AT louismariecharbonniermd immunologicalbiomarkersassociatedwithsurvivalinacohortofargentinianpatientswithcommonvariableimmunodeficiency AT mehdibenamarphd immunologicalbiomarkersassociatedwithsurvivalinacohortofargentinianpatientswithcommonvariableimmunodeficiency AT rubendariomotrichphd immunologicalbiomarkersassociatedwithsurvivalinacohortofargentinianpatientswithcommonvariableimmunodeficiency AT talalachatilamdphd immunologicalbiomarkersassociatedwithsurvivalinacohortofargentinianpatientswithcommonvariableimmunodeficiency AT virginiaeriverophd immunologicalbiomarkersassociatedwithsurvivalinacohortofargentinianpatientswithcommonvariableimmunodeficiency |