High Levels of (Un)Switched Memory B Cells Are Associated With Better Outcome in Patients With Advanced Atherosclerotic Disease

J Am Heart Assoc. 2017 Sep 7;6(9):e005747. doi: 10.1161/JAHA.117.005747.

Abstract

Background: Atherosclerosis is an inflammatory lipid disorder and the main underlying pathology of acute ischemic events. Despite a vast amount of data from murine atherosclerosis models, evidence of B-cell involvement in human atherosclerotic disease is limited. We therefore investigated the association of circulating B-cell subtypes with the occurrence of secondary cardiovascular events in advanced atherosclerotic disease.

Methods and results: This cohort study consists of 168 patients who were included in the Athero-Express biobank between 2009 and 2011. Before surgery, peripheral blood mononuclear cells were isolated and stored in liquid nitrogen. After gentle thawing of the peripheral blood mononuclear cells, different B-cell subtypes including naïve, (un)switched memory, and CD27+CD43+ B1-like B cells, were analyzed by flow cytometry. Univariable and multivariable Cox proportional hazard models were used to analyze associations between B-cell subtypes, circulating antibodies and secondary cardiovascular manifestations during the 3-year follow-up period. Mean age was 70.1±9.6 years, males represented 62.8% of the population, and 54 patients had secondary manifestations during follow-up. High numbers of unswitched memory cells were protective against secondary outcome (hazard ratio, 0.30 [95% CI, 0.13-0.69]; P<0.01). Similar results were obtained for the switched memory cells that also showed to be protective against secondary outcome (hazard ratio, 0.33 [95% CI, 0.14-0.77]; P=0.01).

Conclusions: A high number of (un)switched memory B cells is associated with better outcome following carotid artery endarterectomy. These findings suggest a potential role for B-cell subsets in prediction and prevention of secondary cardiovascular events in patients with atherosclerosis.

Keywords: B lymphocytes; atherosclerosis; carotid endarterectomy; recurrent event.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Autoantibodies / blood
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Carotid Arteries / pathology*
  • Carotid Arteries / surgery
  • Carotid Artery Diseases / immunology*
  • Carotid Artery Diseases / mortality
  • Carotid Artery Diseases / pathology
  • Carotid Artery Diseases / surgery
  • Chi-Square Distribution
  • Endarterectomy, Carotid / adverse effects
  • Endarterectomy, Carotid / mortality
  • Female
  • Flow Cytometry
  • Humans
  • Immunoglobulin M / blood
  • Immunologic Memory*
  • Immunophenotyping / methods
  • Lipoproteins, LDL / immunology
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Myocardial Infarction / etiology
  • Myocardial Infarction / mortality
  • Phenotype
  • Plaque, Atherosclerotic*
  • Proportional Hazards Models
  • Risk Factors
  • Stroke / etiology
  • Stroke / mortality
  • Time Factors
  • Treatment Outcome

Substances

  • Autoantibodies
  • Immunoglobulin M
  • Lipoproteins, LDL
  • oxidized low density lipoprotein