Clin Res Cardiol 107, Suppl 1, April 2018

Maturating B lymphocytes in the setting of acute myocardial infarction

R. Feldtmann1, A. Kümmel1, E. Abdiu1, B. Chamling1, S. B. Felix1, R. Busch1, A. Strohbach1
1Klinik und Poliklinik für Innere Medizin B, Universitätsmedizin Greifswald, Greifswald;
Objective: Acute myocardial infarction (MI) is typically caused by an abrupt blockage of a coronary artery, leading to necrosis of the affected heart tissue. Immediately, distinct leukocyte cell populations infiltrate the injured heart. B cells have come to the forefront as viable targets in various autoimmune diseases, which are associated with increased cardiovascular risk. Here, we address the role of different maturating B cells which orchestrate a variety of adaptive immune responses relevant to human diseases, but that has relatively been neglected in the setting of ischemic injury.

Methods: We quantified the number of different maturating B cell subpopulations in arterial blood of 31 patients (23% women) with acute MI who were 66±15 years old. The study population included 14 patients with ST-segment elevation MI (STEMI) who were 64±14 years old and 17 patients with non-ST-segment elevation MI (NSTEMI) who were 68±15 years old. Myocardial ischemia was determined by coronary angiography. The left ventricular ejection fraction averaged 53% (range of 40-60%) in STEMI and 57% (range of 38-63%) in NSTEMI patients. Absolute cell counts were assessed in whole blood, drawn from the arterial port prior to coronary intervention, by multi-color FACS analysis. Mature CD19+ B cells were further subdivided in CD19+/IgD+/CD27- naïve B cells, CD19+/IgD+/CD27-/CD38++/CD24++ transitional B cells, CD19+/IgD-/CD27++ plasma cells, and CD19+/IgD+/CD27+ memory B cells. Absolute quantification was achieved by means of blood analysis. Results were correlated with plasma markers of severity of myocardial damage. Additionally, 10 healthy individuals (30% women) were included who were 57±7 years old. The study was approved by the local institutional review board, and participants provided witnessed, written informed consent.

Results: Overall, the number of CD19+ B cells was significantly increased in STEMI patients compared to healthy controls (31.9±6.2 x104 versus 13.6±3.3 x104 cells/mL; p=0.026) and NSTEMI group (31.9±6.2 x104 versus 15.9±2.1 cells/mL; p=0.016). Linear regression analysis was performed to correlate total B cell counts with troponin I and creatine kinase plasma levels in MI patients. The multivariate regression model comprised sex, age, current smoking, symptom duration, leukocyte count, and CRP-levels and revealed a strong correlation of the CD19+ B cell counts with the markers of the severity of infarction (ß-coefficients are given in table 1). Further investigation of B cell subpopulations revealed a continuously increased number of cells in STEMI patients compared to healthy individuals and to NSTEMI group (table 1). Noteworthy, only naïve B cells and memory cells show a correlation to troponin I (Pearson r=0.770; p=0.0005 and r=0.717; p=0.0058, respectively) and creatine kinase (Pearson r=0.827; p=0.0005 and r=0.717; p=0.0058, respectively), indicating a prevalent role for these subsets in myocardial damage after MI. Finally, the number of memory cells correlates to the 6 months probability of death from admission, which was calculated from the GRACE Score (Pearson r=0.609; p=0.0466).

Conlusion: Our data indicate a potential relation of elevated B cell counts with adverse outcomes in patients with acute MI. How B cells contribute to the injured heart itself is an area of future investigations.

Table 1

http://www.abstractserver.de/dgk2018/jt/abstracts//V824.htm