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Elevated CD3low double negative T lymphocyte is associated with pneumonia and its severity in pediatric patients.

ABSTRACT: Background:Previous studies have shown that the adaptive immunity function of T cells in disease states correlates with CD3 surface expression closely. During routine assessment of TBNK subsets in peripheral blood of pediatric patients by flow cytometry, we noticed that variable expression levels of CD3 on CD3+CD4-CD8- double-negative T (DNT) lymphocytes in different patients. The objective of this study was to assess the relationship of CD3 expression levels on DNT cells with disease severity. Methods:In this prospective study, we investigated the frequencies of circulating CD4-CD8- DNT cell subsets with CD3low or CD3high phenotype by flow cytometry in 76 pediatric patients with pneumonia, 55 patients with severe pneumonia (SP), and 29 healthy controls (Con). Results:The numbers of circulating DNT cells were similar in all groups; however, the frequency of CD3low DNT cell subsets was significantly increased in patients with pneumonia (p < 0.001) and SP (p < 0.001). The elevated CD3low DNT cell frequency showed a positive correlation with the clinical severity of pneumonia. On sub-group analysis, the frequency of CD3low DNT cells was only elevated in children with pneumonia aged <5 years, while no association was observed with the causative pathogen of pneumonia. Conclusions:These findings suggest that CD3 expression levels on DNT cell subsets of peripheral lymphocytes may be a valuable biomarker for evaluation of immune response in pediatric infectious disease. CD3low DNT cells were elevated in children with pneumonia aged <5 years, which indicates that it may be an important research target in pediatric infectious diseases.

SUBMITTER: Wang Y

PROVIDER: S-EPMC6302782 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Elevated CD3<sup>low</sup> double negative T lymphocyte is associated with pneumonia and its severity in pediatric patients.

Wang Ying Y Lu Wenting W Li Aipeng A Sun Zhengyi Z Wang Liying L

PeerJ 20181218

<h4>Background</h4>Previous studies have shown that the adaptive immunity function of T cells in disease states correlates with CD3 surface expression closely. During routine assessment of TBNK subsets in peripheral blood of pediatric patients by flow cytometry, we noticed that variable expression levels of CD3 on CD3<sup>+</sup>CD4<sup>-</sup>CD8<sup>-</sup> double-negative T (DNT) lymphocytes in different patients. The objective of this study was to assess the relationship of CD3 expression le ...[more]

PMID: 30588404

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Project description:BackgroundPneumococcal community-acquired pneumonia (P-CAP) is a major cause of morbidity and hospitalization. Several host genetics factors influencing risk of pneumococcal disease have been identified, with less information about its association with P-CAP. The aim of the study was to assess the influence of single nucleotide polymorphisms (SNP) within key genes involved in the innate immune response on the susceptibility to P-CAP and to study whether these polymorphic variants were associated with the severity and outcome of the episodes in a cohort of adult Caucasian patients.MethodsSeventeen SNPs from 7 genes (IL-R1, IL-4, IL-10, IL-12B, NFKBIA, NFKBIE, NFKBIZ) were analyzed. For susceptibility, a case-control study including a cohort of 57 adult with P-CAP, and 280 ethnically matched controls was performed. Genetic influence on clinical severity and outcome was evaluated in a prospective observational study including all consecutive adult P-CAP patients from November 2015 to May 2017.ResultsThe NFKBIA polymorphism rs696 and a haplotype combination were associated with susceptibility to P-CAP (OR = 0.62, p = 0.005 and OR = 0.63, p = 0.008, respectively). The SNP IL4 rs2227284 was associated with severe P-CAP (OR = 2.17, p = 0.04). IL-R1 (rs3917267) and IL-10 (rs3024509) variants were related with respiratory failure (OR = 3.31, p = 0.001 and OR = 0.18, p = 0.003, respectively) as well as several haplotype combinations in NFKBIA, NFKBIZ, IL-R1 and IL-10 (p = 0,02, p = 0,01, p = 0,001, p = 0,03, respectively). CURB-65 values were associated with the IL-10 rs3024509 variant (beta = - 0.4, p = 0.04), and with haplotype combinations of NFKBIZ and IL-10 (p = 0.05, p = 0.04, respectively). Genetic variants in IL-10 (rs3024509) and in IL-12B (rs730691) were associated with PSI values (beta = - 0.54, p = 0.01, and beta = - 0.28, p = 0.04, respectively), as were allelic combinations in IL-R1 (p = 0.02) and IL-10 (p = 0.01). Finally, several polymorphisms in the IL-R1 gene (rs13020778, rs2160227, & rs3917267) were associated with the time elapsed until clinical stability (beta = - 0.83, p = 0.03; beta = - 1, p = 0.02 and beta = 1.07, p = 0.008, respectively).ConclusionsA genetic variant in NFKBIA was associated with susceptibility to P-CAP in adult Caucasian patients and genetic variants from key cytokines of the innate immune response (Il-4, IL-10, IL-R1 and IL-12B) and NF-κB inhibitors were associated with different phenotypes of severe P-CAP. If validated, these SNPs may help to identify people at risk of P-CAP or severe P-CAP on which preventive measures could be applied.

Dataset Information

Elevated CD3low double negative T lymphocyte is associated with pneumonia and its severity in pediatric patients.

Publications

Elevated CD3<sup>low</sup> double negative T lymphocyte is associated with pneumonia and its severity in pediatric patients.

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