title: Alterations in circulating T-cell lymphocyte populations in children with obstructive sleep apnea.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Cross-sectional.
  
  
  METHODS
  Kosair Children's Hospital (Louisville, KY, USA) and Comer Children's Hospital (Chicago, IL, USA).
  
  
  METHODS
  Consecutively recruited children being evaluated for habitual snoring.
  
  
  METHODS
  N/A.
  
  
  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-γ (IFN-γ), 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.
authors.affiliation: Section of Pediatric Sleep Medicine, Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Hui-Leng
authors.initials: HL
authors.lastname: Tan
authors.forename: David
authors.initials: D
authors.lastname: Gozal
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Hari P R
authors.initials: HP
authors.lastname: Bandla
authors.forename: Rakesh
authors.initials: R
authors.lastname: Bhattacharjee
authors.forename: Richa
authors.initials: R
authors.lastname: Kulkarni
authors.forename: Leila
authors.initials: L
authors.lastname: Kheirandish-Gozal
mesh_terms: D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D018655:Lymphocyte Count; D008297:Male; D017286:Polysomnography; D020181:Sleep Apnea, Obstructive / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000502:physiology*
keywords: T cell lymphocytes; children; inflammation; sleep apnea