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Human cytomegalovirus (HCMV) remains an important cause of morbidity after allotransplantation, causing a range of direct effects including hepatitis, pneumonitis, enteritis and retinitis. A dominant risk factor for HCMV disease is high level viral replication in blood but it remains unexplained why only a subset of patients develop such diseases. In this detailed study of 25 renal transplant recipients, we show that functional impairment of HCMV specific CD8 T cells in the production of interferon gamma was associated with a 14-fold increased risk of progression to high level replication. The CD8 T-cell impairment persisted during the period of high level replication and was more prominent in patients above 40 years of age (odds ratio = 1.37, p = 0.01) and was also evident in dialysis patients. Threshold levels of functional impairment were associated with an increased risk of future HCMV replication and there was a direct relationship between the functional capacity of HCMV ppUL83 CD8 T cells and HCMV load (R(2)= 0.83). These results help to explain why a subset of seropositive individuals develop HCMV replication and are at risk of end-organ disease and may facilitate the early identification of individuals who would benefit from targeted anti-HCMV therapy after renal transplantation.

Original publication

DOI

10.1111/j.1600-6143.2008.02191.x

Type

Journal article

Journal

Am J Transplant

Publication Date

05/2008

Volume

8

Pages

990 - 999

Keywords

Antiviral Agents, CD8-Positive T-Lymphocytes, Cytomegalovirus, Cytomegalovirus Infections, DNA, Viral, Female, Follow-Up Studies, Ganciclovir, Humans, Interferon-gamma, Kidney Transplantation, Male, Polymerase Chain Reaction, Postoperative Complications, Prospective Studies, Virus Replication