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

Background: T 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.

Methods: A 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.

Results: HD 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.

Conclusion: We 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.