Elevated counts of naïve and memory B cells might be associated with the severity of myocardial damage in the setting of acute myocardial infarction

Abstract

ObjectiveAcute myocardial infarction (AMI) 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 mediating self‐repair and regeneration of the injured tissue as well as pathological autoimmune responses. The latter of which may subsequently lead to ventricular remodeling and heart failure. Hence, regulating this immune response may prove beneficial as an adjunct therapy in the management of AMI. B lymphocytes act as important sensors of pathogens and self‐antigens and promote both protective and autoimmune effects. We explored the role of subtypes of maturating B lymphocytes in the setting of ischemic injury.MethodsWe quantified the number of mature B cells in the arterial blood of 31 AMI patients (23% women, age 66±15 years). Myocardial ischemia was determined by coronary angiography. Additionally, 10 healthy individuals (30% women, age 59±7 years) were included. 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. The total number of cells was normalized to the white blood cell count of the whole blood analysis. Linear regression analysis was performed to associate total B cell counts with troponin I and creatine kinase (CK) plasma levels in MI patients. The multivariable regression model comprised sex, age, current smoking, symptom duration, leukocyte count, and CRP‐levels. Risk assessment for AMI patients was done using the GRACE score, which was calculated using http://www.gracescore.org. The variables that constitute the GRACE score are age, heart rate, systolic blood pressure, and serum creatinine.ResultsThe study population included 14 patients with ST‐segment elevation MI (STEMI) (64±14 years) and 17 patients with non‐ST‐segment elevation MI (NSTEMI) (68±15 years). Mean left ventricular ejection fraction was 53% (40–60%) in STEMI and 57% (38–63%) in NSTEMI patients. The number of CD19+ B cells was significantly increased in STEMI patients compared to controls (31.9±6.2 ×104 vs. 13.6±3.3 ×104 cells/mL; p=0.026) and NSTEMI group (31.9±6.2 ×104 vs. 15.9±2.1 cells/mL; p=0.016). Results were associated with plasma troponin I and CK and revealed a strong relation of the CD19+ B cells count with these markers of the severity of infarction (table 1). Further, investigation of B cell subpopulations revealed a higher number of cells in STEMI patients compared to controls 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 CK (Pearson r=0.827; p=0.0005 and r=0.717; p=0.0058, respectively). 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).ConclusionOur data indicate a potential relation of elevated B cell counts with adverse outcomes in patients with AMI. Further, the strong association of naïve and memory B cells with markers of myocardial damage suggests a prevalent role for these subsets. How B cells contribute to the injured heart itself is an area of future investigations.Support or Funding InformationThis study is funded by the German Centre for Cardiovascular Research (DZHK) Partner Site Greifswald, Greifswald, Germany.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.