Coronary Artery Bypass Grafting Is Associated with Significant Pertubation of Circulating Dendritic Cell Populations

Introduction

Coronary artery bypass grafting (CABG) with sternotomy is a complex procedure that triggers an overall systemic inflammatory response as a result of exposing patient blood to the bypass circuitry which is hypothesised to contribute to adverse patient outcomes including infection and prolonged ICU length of stay. Dendritic cells (DC) are antigen presenting cells that link the innate and adaptive immune response and can be divided into two main subsets; myeloid DC (mDC; HLA-DR⁺CD11c⁺) and plasmacytoid DC (pDC; HLA-DR⁺CD11c^-CD123⁺). Circulating immature DC have a high phagocytosis and antigen-processing capacity and mature in response to inflammation as they migrate to lymphoid organs to regulate T cells. Extracorporeal circuitry associated with CABG has been reported to trigger a complex inflammatory reaction where pro- and anti- inflammatory cytokines are produced, leucocyte subsets such as monocytes become activated and changes to the composition of circulating cell populations occur which may be associated with adverse patient outcomes following surgery. Given the central role DC plays in the patient immune response, this study aimed to address the limited understanding of how DC function changes during cardiac surgery by assessing changes in absolute cell number of DC populations.

Methods

Patient whole blood (EDTA) was collected from CABG patients (n=33) at 5 time-points (Admission, Peri-operative, ICU, Day 3, Day 5). The absolute count of DC subsets (mDC Lineage^-HLA-DR⁺CD11c⁺; pDC Lineage^-HLA-DR⁺CD11c^-CD123⁺) and the number of DC expressing specific activation and adhesion markers (CD9, CD38, CD40, CD80, CD83, CD86) was assessed using Trucount tubes (BD Biosciences, Australia). A repeated measure one-way ANOVA with Dunnett's post-test was used for the analysis of absolute cell counts with the admission sample used as the comparator baseline. P values <0.05 were considered significant

Results

A significant decrease in circulating mDC was observed during CABG surgery. A recovery in mDC numbers towards baseline was evident by day 5 post-surgery. The number of mDC expressing CD38, CD40, CD80, CD83 and CD86 were also reduced, suggesting mDC in circulation maintained an immature phenotype. Of note, CD40 expressing mDC numbers were reduced during surgery before a dramatic increase during the ICU period followed by a return towards baseline levels at day 5. In contrast to mDC, circulating pDC numbers significantly increased during surgery before decreasing during the ICU period and regressing towards normal baseline levels by day 5. The number of pDC expressing CD38 increased during surgery before regressing towards baseline at day 5.

Conclusion

These data demonstrate that CABG is associated with significant perturbation of circulating DC populations. While numbers of mDC decreased, numbers of pDC increased suggesting CABG resulted in differential modulation of these two DC subsets. Of note both DC subsets demonstrated a toleregenic phenotype rather than an activatory profile. Decreased numbers of mDC during surgery suggest impaired functional capacity potentially increasing the risk of infection post-surgery. Normalisation towards baseline levels was observed by day 5 post-surgery for both mDC and pDC. We are currently assessing whether changes in the DC cell count and phenotype is associated with patient outcomes and may serve as a predictive biomarker for adverse patient outcomes.