Monitoring cytomegalovirus T-cell immunity in small bowel/multivisceral transplant recipients.

BACKGROUND: Cytomegalovirus (CMV) is a major cause of graft failure and posttransplantation mortality in intestinal/multivisceral transplantation. CMV infection exhibits a wide range of clinical manifestations from asymptomatic infection to severe CMV disease. STUDY'S PURPOSE: The purposes of this study were to assess the utility of measuring CMV-specific cellular immunity in bowel/multivisceral transplant recipients and to provide additional information on the risk of infection and development of CMV disease. METHODS: We studied 10 bowel/multivisceral transplant recipients to investigate the kinetics of CMV infection using real-time polymerase chain reaction (on blood and biopsy tissue samples) and CMV-specific T-cell reconstitution by Enzyme-linked ImmunoSPOT Assay (ELISPOT) that enumerates Interferon-gamma-secreting CMV-specific T cells upon in vitro stimulation with viral antigens (pp65 and IE-1). RESULTS: All patients were seropositive for CMV. According to the pattern of T-cell reconstitution occurring either within the first month after transplantation or later, patients were classified as early (n = 7) or late responders (n = 3). Clinically, early responder patients (3/7; 43%) experienced asymptomatic or mild CMV infections, whereas all late responders (3/3; 100%) developed moderate or severe CMV disease. A reduction in mean and peak CMV viral load was observed in early responders, whereas the onset time of infection did not differ significantly between early and late CMV responders. CONCLUSIONS: A good and early reconstitution of CMV-specific T-cell immune responses after transplantation is a critical determinant in controlling CMV infections. Simultaneous monitoring of CMV infection and CMV-specific T-cell immunity predicts T-cell-mediated control of CMV infection.

Early and late virological monitoring of cytomegalovirus, Epstein-Barr virus, and human herpes virus 6 infections in small bowel/multivisceral transplant recipients.

BACKGROUND: Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) are the major causes of graft failure and posttransplantation mortality among small bowel and multivisceral transplantations (SB/MVT). Little is known about human herpes virus 6 (HHV-6) infections in transplant recipients. STUDY PURPOSE: The purposes of this study were to analyze the clinical relevance of CMV, EBV, and HHV-6 infections after small bowel transplantation and to establish whether routine monitoring for HHV-6 infection should be recommended for the prevention of severe complications in this population. METHODS: Ten adult patients were monitored based on CMV, EBV, and HHV6 DNA quantifications in blood and biopsy tissue samples. Three patients were monitored for at least 5 months (early period) and 7 patients were monitored for 1 to 5 years after transplantation (late period). RESULTS: In the early period, despite prophylaxis all 3 patients developed symptomatic CMV infections: 1 fever/diarrhea, 1 enteritis and rejection, as well as 1 fever and pneumonia. Only 1 patient developed EBV and HHV-6 infections. The average time of onset of CMV infection was 3 months after transplantation and only 24 days for HHV6 infection. In the late period, of the 7 SB/MVT recipients only 1 developed an EBV infection at 2 years after transplantation. No CMV or HHV-6 infections were identified in any patient. CONCLUSIONS: CMV infection is a major cause of organ disease and rejection in the early period after transplantation. EBV infection in adult recipients must be considered also in the late period, particularly in association with severe immunosuppression. Because HHV-6 infection occurs earlier than CMV/EBV, it may serve as an indicator for more intense virological surveillance.