Alterations in Circulating T-Cell Lymphocyte Populations in Children with Obstructive Sleep Apnea

被引:40
作者
Tan, Hui-Leng [1 ]
Gozal, David [1 ]
Wang, Yang [1 ]
Bandla, Hari P. R. [1 ]
Bhattacharjee, Rakesh [1 ]
Kulkarni, Richa [1 ]
Kheirandish-Gozal, Leila [1 ]
机构
[1] Univ Chicago, Pritzker Sch Med, Dept Pediat, Sect Pediat Sleep Med,Biol Sci Div, Chicago, IL 60637 USA
基金
美国国家卫生研究院;
关键词
T cell lymphocytes; children; inflammation; sleep apnea; PERIPHERAL-BLOOD; ENDOTHELIAL DYSFUNCTION; DNA METHYLATION; OBESITY; ASTHMA; ATHEROSCLEROSIS; PROLIFERATION; ATHEROGENESIS; INFLAMMATION; PERFORMANCE;
D O I
10.5665/sleep.2724
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Study Objectives: Changes in lymphocyte phenotype and functionality have been described in adult patients with obstructive sleep apnea (OSA). We hypothesized that OSA is associated with T lymphocyte alterations in children, particularly in T regulatory lymphocytes (T regs), and aimed to characterize circulating T lymphocyte subsets in children with OSA. Design: Cross-sectional. Setting: Kosair Children's Hospital (Louisville, KY, USA) and Comer Children's Hospital (Chicago, IL, USA). Participants: Consecutively recruited children being evaluated for habitual snoring. Interventions: N/A. Measurements and Results: Overnight polysomnography (PSG) was performed and a fasting blood sample was obtained from the patients. Flow cytometry was performed on peripheral blood mononuclear cells stained for CD3, CD4, CD8, CD25, FOXP3, interleukin-4 (IL-4), interferon-gamma (IFN-gamma), and IL-17. Patients were divided into three groups based on their PSG: controls (apnea-hypopnea indices [AHI] < 1/h total sleep time [TST]), mild OSA (1 <= AHI < 5/hTST), moderate-severe OSA (AHI >= 5/h TST). The percentage of CD4+ and T reg lymphocytes differed across groups. Children with moderate-severe OSA had significantly reduced T reg than control children (median [interquartile range] 4.8 [3.8-5.7% CD4+] versus 7.8 [7.0-9.2% CD4+]; P < 0.001). There were also significant differences in the percentage of T helper 1 (Th1) lymphocytes and in Th1: Th2 ratios between groups. Children with moderate-severe OSA had increased Th1 cells (P = 0.001) and Th1: Th2 ratios (P = 0.0026) compared with children with mild OSA and control children. Associations between AHI and T reg (P = 0.0003; r = -0.46), CD4+ lymphocytes (P = 0.0047; r = -0.37), and Th1: Th2 ratios (P = 0.0009; r = 0.43) emerged. In addition, the percentage of T reg was inversely correlated with Th1: Th2 ratios (P = 0.029; r = -0.29). Conclusions: Pediatric OSA is associated with reduced T reg population and altered Th1: Th2 balance toward Th1 predominance, suggesting a shift to a proinflammatory state. The changes in lymphocytic phenotypes associated with OSA may contribute to the variance in systemic inflammation and downstream morbidities associated with this condition.
引用
收藏
页码:913 / 922
页数:10
相关论文
共 70 条
[1]   Functional diversity of helper T lymphocytes [J].
Abbas, AK ;
Murphy, KM ;
Sher, A .
NATURE, 1996, 383 (6603) :787-793
[2]   Cytokine network and T cell immunity in atherosclerosis [J].
Ait-Oufella, Hafid ;
Taleb, Soraya ;
Mallat, Ziad ;
Tedgui, Alain .
SEMINARS IN IMMUNOPATHOLOGY, 2009, 31 (01) :23-33
[3]   T Regulatory Lymphocytes Prevent Angiotensin II-Induced Hypertension and Vascular Injury [J].
Barhoumi, Tlili ;
Kasal, Daniel A. ;
Li, Melissa W. ;
Shbat, Layla ;
Laurant, Pascal ;
Neves, Mario F. ;
Paradis, Pierre ;
Schiffrin, Ernesto L. .
HYPERTENSION, 2011, 57 (03) :469-U245
[4]   Endothelial Dysfunction in Children Without Hypertension Potential Contributions of Obesity and Obstructive Sleep Apnea [J].
Bhattacharjee, Rakesh ;
Kim, Jinkwan ;
Alotaibi, Wadha H. ;
Kheirandish-Gozal, Leila ;
Capdevila, Oscar Sans ;
Gozal, David .
CHEST, 2012, 141 (03) :682-691
[5]   Natural and Adaptive Foxp3+ Regulatory T Cells: More of the Same or a Division of Labor? [J].
de Lafaille, Maria A. Curotto ;
Lafaille, Juan J. .
IMMUNITY, 2009, 30 (05) :626-635
[6]   Sleep disturbance and daytime symptoms in wheezing school-aged children [J].
Desager, KN ;
Nelen, V ;
Weyler, JJJ ;
De Backer, WA .
JOURNAL OF SLEEP RESEARCH, 2005, 14 (01) :77-82
[7]   Lymphocyte activation as a possible measure of atherosclerotic risk in patients with sleep apnea [J].
Dyugovskaya, L ;
Lavie, P ;
Lavie, L .
AUTOIMMUNE DISEASES AND TREATMENT: ORGAN-SPECIFIC AND SYSTEMIC DISORDERS, 2005, 1051 :340-350
[8]   Activated CD8+ T-lymphocytes in obstructive sleep apnoea [J].
Dyugovskaya, L ;
Lavie, P ;
Hirsh, M ;
Lavie, L .
EUROPEAN RESPIRATORY JOURNAL, 2005, 25 (05) :820-828
[9]   Phenotypic and functional characterization of blood γδ T cells in sleep apnea [J].
Dyugovskaya, L ;
Lavie, P ;
Lavie, L .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2003, 168 (02) :242-249
[10]   Heterogeneity of severe asthma in childhood: Confirmation by cluster analysis of children in the National Institutes of Health/National Heart, Lung, and Blood Institute Severe Asthma Research Program [J].
Fitzpatrick, Anne M. ;
Teague, W. Gerald ;
Meyers, Deborah A. ;
Peters, Stephen P. ;
Li, Xingnan ;
Li, Huashi ;
Wenzel, Sally E. ;
Aujla, Shean ;
Castro, Mario ;
Bacharier, Leonard B. ;
Gaston, Benjamin M. ;
Bleecker, Eugene R. ;
Moore, Wendy C. .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2011, 127 (02) :382-U973