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. 2024 Jul 23;3(4):100311.
doi: 10.1016/j.jacig.2024.100311. eCollection 2024 Nov.

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

Adrian Kahn  1   2   3 , Gabriela Luque  4 , Eduardo Cuestas  2   5 , Ana Basquiera  2   4 , Brenda Ricchi  4 , Klaus Schmitz-Abe  6   7   8   9 , Louis-Marie Charbonnier  6   7 , Mehdi Benamar  6   7 , Ruben Dario Motrich  3   10   11 , Talal A Chatila  6   7 , Virginia E Rivero  3   10   11
Affiliations

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

Adrian Kahn et al. J Allergy Clin Immunol Glob. .

Abstract

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.

Keywords: B-cell subpopulations; CVID; T cells; WES; mortality; outcomes; score.

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Conflict of interest statement

This study was funded by the 10.13039/100000002National Institutes of Health/10.13039/100000060National Institute of Allergy and Infectious Diseases (grant no. 5R01AI128976), Agencia Nacional de Promoción Científica y Tecnológica (grant no. PICT 2021-0840), and Secretaría de Ciencia y Tecnología de la Universidad Nacional de Córdoba (grant no. 33620180100584CB). Disclosure of potential conflict of interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Fig 1
Fig 1
Probability of death according to circulating immune subset counts. A, Probability of death according to circulating CD4+ T-cell counts. B, Probability of death according to circulating IgM/IgD memory switched B-cell counts. C, Probability of death according to circulating NK-cell counts. The outcome studied is the cumulative incidence of death.
Fig 2
Fig 2
Cutoff values for immunological variables that might predict CVID survival. ROC curves for differential CD4+ cells, memory switched B cells, and NK cells are shown. The AUC is 0.87 for CD4+ T cells and 0.92 for memory switched B cells and NK cells.
Fig 3
Fig 3
Construction of a disease outcome and survival score. A, Points assigned for CD4+ T cells, memory switched B cells, and NK cells when greater than calculated cutoff values. B, ROC curve showing a cutoff score point of 2.5, predictive of high mortality risk in patients with CVID.
Fig 4
Fig 4
CVID probability survival analysis. Kaplan-Meier curves showing 10-year survival probability in patients with CVID with CD4+ T cells, memory switched B cells, and NK cells when greater than or less than the cutoff values.
See this image and copyright information in PMC

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