TY - JOUR
T1 - High levels of (un)switched memory B cells are associated with better outcome in patients with advanced atherosclerotic disease
AU - Meeuwsen, John A.L.
AU - van Duijvenvoorde, Amerik
AU - Gohar, Aisha
AU - Kozma, Maria O.
AU - van de Weg, Sander M.
AU - Gijsberts, Crystel M
AU - Haitjema, Saskia
AU - Björkbacka, Harry
AU - Fredrikson, Gunilla N.
AU - de Borst, Gert J.
AU - den Ruijter, Hester M
AU - Pasterkamp, Gerard
AU - Binder, Christoph J.
AU - Hoefer, Imo E
AU - de Jager, Saskia C A
PY - 2017/9/1
Y1 - 2017/9/1
N2 - 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.
AB - 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.
KW - Atherosclerosis
KW - B lymphocytes
KW - Carotid endarterectomy
KW - Recurrent event
UR - http://www.scopus.com/inward/record.url?scp=85029762322&partnerID=8YFLogxK
U2 - 10.1161/JAHA.117.005747
DO - 10.1161/JAHA.117.005747
M3 - Article
C2 - 28882820
AN - SCOPUS:85029762322
SN - 2047-9980
VL - 6
JO - Journal of the American Heart Association
JF - Journal of the American Heart Association
IS - 9
M1 - e005747
ER -