Circulating autoantibodies against neuroblastoma suppressor of tumorigenicity 1 (NBL1): A potential biomarker for coronary artery disease in patients with obstructive sleep apnea

PLoS One. 2018 Mar 29;13(3):e0195015. doi: 10.1371/journal.pone.0195015. eCollection 2018.

Abstract

Objective: Although severe obstructive sleep apnea (OSA) is an important risk factor for atherosclerosis-related diseases including coronary artery disease (CAD), there is no reliable biomarker of CAD risks in patients with OSA. This study aimed to test our hypothesis that circulating autoantibodies against neuroblastoma suppressor of tumorigenicity 1 (NBL1-Abs) are associated with the prevalence of CAD in patients with OSA.

Methods: Eighty-two adults diagnosed with OSA by polysomnography, 96 patients with a diagnosis of acute coronary syndrome (ACS) and 64 healthy volunteers (HVs) were consecutively enrolled. Serum samples were collected from patients with OSA at diagnostic polysomnography and from patients with ACS at disease onset. Serum NBL1-Ab level was measured by amplified luminescence proximity homogeneous assay and its association with clinical variables related to atherosclerosis was evaluated.

Results: NBL1-Ab level was significantly elevated in patients with both OSA and ACS compared with HVs. Subgroup analyses showed that NBL1-Ab level was markedly higher in patients with severe OSA and OSA patients with a history of CAD. Weak associations were observed between NBL1-Ab level and apnea-hypopnea index, age, mean SpO2 and arousal index, whereas significantly higher NBL1-Ab levels were observed in OSA patients with a history of CAD than in those without a history of CAD. Sensitivity analysis using a logistic regression model also demonstrated that increased NBL1-Ab levels were associated with the previous history of CAD in patients with OSA.

Conclusions: Elevated NBL1-Ab levels may be associated with the prevalence of CAD in patients with OSA, which needs to be confirmed further.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Autoantibodies / blood*
  • Autoantibodies / immunology
  • Biomarkers / blood
  • Cell Cycle Proteins
  • Coronary Artery Disease / complications*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Proteins / immunology*
  • Sleep Apnea, Obstructive / blood*
  • Sleep Apnea, Obstructive / complications*
  • Sleep Apnea, Obstructive / immunology

Substances

  • Autoantibodies
  • Biomarkers
  • Cell Cycle Proteins
  • NBL1 protein, human
  • Proteins

Grants and funding

This study was supported in-part by a grant to The Intractable Respiratory Diseases and Pulmonary Hypertension Research Group, the Ministry of Health, Labor and Welfare, Japan (http://www.mhlw.go.jp/english/index.html); the Japan Agency for Medical Research and Development (AMED, https://www.amed.go.jp), Japan Society for the Promotion of Science (JSPS) KAKENHI (Grant number 16K09528, https://www.jsps.go.jp/index.html) and Grants-in-Aid of the Japan Science and Technology Agency (JST) in Japan (Exploratory Research No. 14657335, http://www.jst.go.jp/index.html). There was no additional external funding received for this study. These funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript.