Abstract
Postoperative atrial fibrillation (POAF) is assumed as a complex and multifactorial interaction of different pathogenic factors. Data suggests an inflammatory process as the main trigger of this specific type of atrial fibrillation. CD8+ T lymphocytes that lack the surface protein CD28 were found to be crucially involved in chronic inflammatory processes within the cardiovascular system. Of utmost interest, these so-called CD8+CD28null T cells are known to present with autoaggressive behavior and deleterious cytotoxic effects on human tissue. A total of 129 patients undergoing elective cardiac valve and/or coronary artery bypass graft surgery were enrolled. Fluorescence-activated cell sorting was performed to investigate lymphocyte subsets. Patients were stratified in two subgroups according to patients developing POAF (n = 60) and individuals free of POAF (n = 69). Comparing patients developing POAF to individuals free of POAF, the fraction of CD8+ lymphocytes was significantly higher in individuals developing POAF (30.5% [POAF] vs. 25.7% [no-POAF]; p = 0.021). Interestingly, also the fraction of CD8+CD28null T lymphocytes was significantly higher in the POAF subgroup (66.7% [POAF] vs. 61.6% [non-POAF]; p = 0.043). Multivariate logistic regression proved that the fraction of CD8+CD28null cells is a strong and independent prognosticator for the development of POAF with an adjusted odds ratio per 1 standard deviation of 3.21 (95% confidence interval 1.01-10.18; p = 0.048). We found that cytotoxic CD8+CD28null T lymphocytes proved to be a strong and independent predictor for the development of POAF after elective cardiac surgery. Our results potentially indicate an autoimmune impact of this preexisting, highly cytotoxic T cell subset in the pathogenesis of POAF.
Highlights
The study sought to assess the impact of cellular immunity on the development of post-operative atrial fibrillation (POAF)
Detailed baseline characteristics for distribution of conventional risk factors and laboratory parameters stratified in patients developing POAF and individuals free of POAF are shown in Supplementary Table 1
That the CD4+CD28null T cell subset is associated with AF in chronic cardiac inflammation, we aimed to examine its association with the first onset of POAF after surgical conditions, representing a strong stimulus for acute cardiac inflammation
Summary
The study sought to assess the impact of cellular immunity on the development of POAF. While various types of AF are known in clinical practice posing a well investigated field in cardiovascular research, a specific type of AF occurring after cardiovascular surgery is still incompletely understood[2] This so called post-operative atrial fibrillation (POAF), represents a common complication after surgical intervention with a reported incidence ranging from 15 to more than 45%3. Recent evidence found a strong association of complement system activation and pro-inflammatory cytokines, mainly released by lymphocytes, with the onset of POAF – hinting to a potential impact of cellular immunity on the cardiac conduction system and in particular atrial fibrosis[7,8]. CD4+ T lymphocytes lacking the surface-protein CD28 are crucially involved in inflammatory processes While these so-called CD4+CD28null T cells are rarely expressed in healthy individuals, their fraction strongly expands during the course of chronic inflammation. Based on longstanding inflammatory conditions, CD4+CD28+ T lymphocytes lose their expression of the CD28 antigen and their sensitivity www.nature.com/scientificreports/
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