Kahn Adrian, Luque Gabriela, Cuestas Eduardo, Basquiera Ana, Ricchi Brenda, Schmitz-Abe Klaus, Charbonnier Louis-Marie, Benamar Mehdi, Motrich Ruben Dario, Chatila Talal A, Rivero Virginia E
Servicio de Alergia e Inmunología Clínica, Hospital Privado Universitario de Córdoba, Córdoba, Argentina.
Instituto Universitario de Ciencias Biomédicas de Córdoba, Córdoba, Argentina.
J Allergy Clin Immunol Glob. 2024 Jul 23;3(4):100311. doi: 10.1016/j.jacig.2024.100311. eCollection 2024 Nov.
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.
We sought to develop a mortality predictive score on the basis of the immunophenotypes and genotypes of patients with CVID.
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.
Alive (15) and deceased (6) patients were compared. Univariate analysis showed significant differences in CD4 T cells ( = .002), natural killer (NK) cells ( = .001), and memory switched B cells ( = .001) between groups. Logistic regression analysis showed a negative correlation between CD4, NK, and memory switched Bcell 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.
A score to predict mortality is proposed on the basis of CD4 T, NK, and memory switched B-cell counts in patients with CVID.
常见变异型免疫缺陷（CVID）是免疫缺陷病中最常见的有症状综合征。尽管CVID免疫病理学的几个方面已得到阐明，但死亡率的预测因素仍未完全明确。仅约30%的患者可确定遗传病因。
我们试图基于CVID患者的免疫表型和基因型制定一个死亡率预测评分。
对阿根廷科尔多瓦诊断为CVID的21例患者的临床和实验室数据进行分析。通过流式细胞术进行免疫表型分析。通过全外显子测序鉴定与CVID相关的突变。
对存活（15例）和死亡（6例）患者进行比较。单因素分析显示两组间CD4 T细胞（P = 0.002）、自然杀伤（NK）细胞（P = 0.001）和记忆转换B细胞（P = 0.001）存在显著差异。逻辑回归分析显示，CD4、NK和记忆转换B细胞计数与10年生存率呈负相关（CD4 T细胞：比值比[OR]，1.01；95%可信区间[CI]，1.001 - 1.020；NK细胞：OR，1.07；95% CI，1.02 - 1.17；记忆转换B细胞：OR，26.23；95% CI，2.06 - 2651.96）。受试者工作特征曲线分析确定了每个参数的生存临界值（CD4 T细胞：546个细胞/mL；曲线下面积[AUC]，0.87；敏感性，60%；特异性，100%；记忆转换B细胞：0.84个细胞/mL；AUC，0.92；敏感性，100%；特异性，85%；NK细胞：45个细胞/mL；AUC，0.92；敏感性，83%；特异性，100%）。对该队列中14例患者（9例女性和5例男性）的基因分析显示，6例患者存在与免疫缺陷病相关的突变。
基于CVID患者的CD4 T细胞、NK细胞和记忆转换B细胞计数，提出了一个预测死亡率的评分。
