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

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.