High levels of (un)switched memory B cells are associated with better outcome in patients with advanced atherosclerotic disease

John A.L. Meeuwsen, Amerik van Duijvenvoorde, Aisha Gohar, Maria O. Kozma, Sander M. van de Weg, Crystel M Gijsberts, Saskia Haitjema, Harry Björkbacka, Gunilla N. Fredrikson, Gert J. de Borst, Hester M den Ruijter, Gerard Pasterkamp, Christoph J. Binder, Imo E Hoefer, Saskia C A de Jager

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article numbere005747
JournalJournal of the American Heart Association
Volume6
Issue number9
DOIs
Publication statusPublished - 2017 Sept 1

Subject classification (UKÄ)

  • Cardiac and Cardiovascular Systems

Free keywords

  • Atherosclerosis
  • B lymphocytes
  • Carotid endarterectomy
  • Recurrent event

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