Cytomegalovirus Prevalence and Transmission After Islet Allograft Transplant in Patients with Type 1 Diabetes Mellitus

Abstract

Cytomegalovirus (CMV) serological status of transplant donors and recipients has important implications on antiviral prophylaxis, morbidity/mortality, donor selection and hospital stay. We evaluated CMV prevalence in our islet transplant candidates (ITC) in comparison with organ donors. We correlated the CMV serological status of our ITC with serology for Epstein-Barr virus and Parvovirus B19, auto-antibodies, patient's age, age at DM onset, duration of DM, gender, race, ABO group, HLA haplotype and C-peptide levels. Cytomegalovirus transmission after islet transplant using the Edmonton regimen was also evaluated. Cytomegalovirus seropositivity varied according to patient group, age, gender and race. Type 1 DM patients had reduced odds of CMV seropositivity when compared with organ donors. In all groups studied, older patients, females, and non-Caucasians were more likely to be CMV seropositive. In addition, no CMV reactivation, infection or disease was observed among our transplanted patients using this steroid-free regimen even after donor/recipient CMV mismatch.

Effects of Acute Cytomegalovirus Infection on Rat Islet Allograft Survival

“…It might be argued that, due to the systemic CMV infection, the infection-induced islet compared to the nontreated CMV-infected group, but this did not reach statistical significance. The animals graft failure is not of any clinical relevance, since systemic viremia is rarely observed after clinical islet transthat successfully restored normoglycemia demonstrated similar islet graft failure rates as the nontreated CMVplantation (2,6,8, 19,20,63). However, the absence of systemic viremia after clinical islet transplantation may infected recipients, which was significantly accelerated compared to the MOCK-infected controls (p < 0.05 ganbe directly attributed to the use of ganciclovir prophylaxis (2,6, 19,20).…”

“…The animals graft failure is not of any clinical relevance, since systemic viremia is rarely observed after clinical islet transthat successfully restored normoglycemia demonstrated similar islet graft failure rates as the nontreated CMVplantation (2,6,8, 19,20,63). However, the absence of systemic viremia after clinical islet transplantation may infected recipients, which was significantly accelerated compared to the MOCK-infected controls (p < 0.05 ganbe directly attributed to the use of ganciclovir prophylaxis (2,6, 19,20). However, when we studied the effects ciclovir-treated recipients vs. controls, CMV-infected recipients vs. ganciclovir-treated recipients not significant, of ganciclovir in combination with a CMV infection, we also found a reduction in graft survival, despite the suclog-rank test) (Fig.…”

“…Together with a high treatments on islet graft survival (11,57). Transplantation was considered successful when nonfasting blood degree of CMV mismatches between islet donors and recipients, especially the R−/D+ combination (20), these glucose concentrations reached levels below 10 mmol/ L. One day after transplantation, the islet graft recipients studies clearly point to a role of CMV in islet graft failure.…”

“…In immunocompetent animals, the infection develops asymptomatic, whereas tation. Before this report, studies that addressed the CMV issue in islet transplantation mostly focused on the low in immunocompromized rats it develops in a generalized infection, characterized by hepatitis, splenitis, and throm-CMV seroconversion rates and the absence of CMV disease after transplantation (2,8,19,20,63). This absence of bocytopenia (51,52).…”

Fully MHC-Disparate Mixed Hemopoietic Chimeras Show Specific Defects in the Control of Chronic Viral Infections

“…To date, the underlying immune mechanisms for these observations have not been defined. Given the clinical importance in transplantation of persistent pathogens such as hepatitis C virus, polyoma BK virus, CMV, EBV, and more recently LCMV (27)(28)(29)(30)(31)(32)(33), coupled with the desire to apply mixed chimerism approaches in both living and deceased donor organ transplantation with varying degrees of MHC disparity (5,34), it is imperative that studies be undertaken to interrogate the immune competence of allogeneic mixed chimeras, to understand mechanisms of immunodeficiency, and to develop strategies to maintain or restore protective immunity. In the current study, we demonstrate that there are profound defects in the control of chronic pathogenic infections in fully MHC-disparate mixed chimeric mice.…”