CD73 as a T cell dysfunction marker predicting cardiovascular and infection events in patients undergoing hemodialysis

Abstract

BackgroundT cell dysfunction observed in patients undergoing hemodialysis (HD) has been linked to an extremely high morbidity of cardiovascular events (CVEs) and infections. The cell-surface 5′-nucleotidase CD73 sets the balance between pro-inflammatory nucleotides and anti-inflammatory adenosine. MethodsA total of 395 patients who had been receiving HD for at least six months were evaluated for proportions of CD73+ cells in both the CD4+ T cell and CD8+ T cell compartment and followed for one year to document CVEs and infections. Differences in the proportions of CD73-expressingT cells between healthy controls and patients undergoing HD were compared. The relationship between CD73+ T cells and clinical outcomes was analyzed using the Kaplan–Meier curve and Cox regression. ResultsHD was significantly related to a lower fraction of CD4+CD73+ T cells. In patients on HD, lower proportions of CD4+ CD73+T cells and CD8+ CD73+T cells were both associated with systemic inflammation and T cell terminal differentiation. More importantly, a lower CD4+CD73+T cell ratio independently predicted CVEs and infection in these patients. ConclusionWe identified CD73 as a T cell dysfunction marker predicting cardiovascular and infection events in patients undergoing HD, which provides a potential target in future studies of uremia-related immune dysfunction.