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

Meeuwsen, John A.L.; van Duijvenvoorde, Amerik; Gohar, Aisha; Kozma, Maria O.; van de Weg, Sander M.; Gijsberts, Crystel M; Haitjema, Saskia; Björkbacka, Harry LU ; Fredrikson, Gunilla N. LU and de Borst, Gert J., et al. (2017) In Journal of the American Heart Association 6(9).
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... (More)

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.

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published
subject
keywords
Atherosclerosis, B lymphocytes, Carotid endarterectomy, Recurrent event
in
Journal of the American Heart Association
volume
6
issue
9
publisher
Wiley-Blackwell
external identifiers
  • scopus:85029762322
  • pmid:28882820
ISSN
2047-9980
DOI
10.1161/JAHA.117.005747
language
English
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yes
id
2f2fd028-3667-437b-bfee-da05774b6797
date added to LUP
2017-10-09 16:28:19
date last changed
2017-11-14 09:49:33
@article{2f2fd028-3667-437b-bfee-da05774b6797,
  abstract     = {<p>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<sup>+</sup>CD43<sup>+</sup> 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 &lt; 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.</p>},
  articleno    = {e005747},
  author       = {Meeuwsen, John A.L. and van Duijvenvoorde, Amerik and Gohar, Aisha and Kozma, Maria O. and van de Weg, Sander M. and Gijsberts, Crystel M and Haitjema, Saskia and Björkbacka, Harry and Fredrikson, Gunilla N. and de Borst, Gert J. and den Ruijter, Hester M and Pasterkamp, Gerard and Binder, Christoph J. and Hoefer, Imo E and de Jager, Saskia C A},
  issn         = {2047-9980},
  keyword      = {Atherosclerosis,B lymphocytes,Carotid endarterectomy,Recurrent event},
  language     = {eng},
  month        = {09},
  number       = {9},
  publisher    = {Wiley-Blackwell},
  series       = {Journal of the American Heart Association},
  title        = {High levels of (un)switched memory B cells are associated with better outcome in patients with advanced atherosclerotic disease},
  url          = {http://dx.doi.org/10.1161/JAHA.117.005747},
  volume       = {6},
  year         = {2017},
}