TNF-α Production by Monocytes Stimulated With Epstein-Barr Virus–Peptides as a Marker of Immunosuppression-Related Adverse Events in Kidney Transplant Recipients

Infections and cancers now outnumber rejection as a cause of morbidity in transplant recipients, likely as a result of over-immunosuppression. Currently, there is no clinical tool to detect over-immunosuppression. We recently reported that tumor necrosis factor alpha (TNF-α) production by CD14+CD16+ intermediate monocytes, following ex vivo stimulation by Epstein-Barr virus–peptides, could identify over-immunosuppressed patients. We conducted a pilot study the assay using 142 peripheral blood mononuclear samples from a cohort of 71 kidney transplant recipients. Patients were classified as cases or controls according to the occurrence of opportunistic infection, recurring bacterial infections or de novo neoplasia in the 12 months following blood collection. We used both the classifier rule and a threshold of