Some limitations of this study
Some limitations of this study must be noted. First, since the pretransplant evaluation of the T-cell immune response was performed just before transplantation, we cannot establish whether samples obtained at different times before the transplant would offer similar results, since end terminal disease may affect patient\'s immunity, including the CMV-specific T-cell immune response. Second, the low incidence of CMV disease in our cohort probably determined that no significant association between having pretransplant CMV-specific T-cell immune response and no developing CMV disease after transplantation was found. Although other variables expressing the absence of self-resolved CMV infection such as high viraemia and pre-emptive therapy were used, larger studies are needed. However, other markers, such as high viral loads, have recently been reported as a surrogate marker of CMV disease . And third, we were not able to establish a cut-off higher than 0.25% that was more strongly associated with protection since sensibility, specificity, and negative predictive values were not high enough to be applied in clinical practice. This fact does not invalidate the present study since it Irinotecan is the first time that it has been demonstrated that pretransplant CMV-specific cellular immunity is an independent factor associated with controlling viraemias >2000 IU/mL and with the administration of treatment after transplantation. These results also suggest that, although the CMV-specific immune response is important in determining the post-transplantation outcome of CMV infection, it may not be sufficient and other immunological factors may be also involved.
Transparency declaration The authors declare no conflict of interest. This study was funded by from the Instituto de Salud Carlos III (grant number: PI11-02800; PI11-01357; PI14-00165), and co-financed by European Development Regional Fund ‘A way to achieve Europe’ ERDF, Spanish Network for the Research in Infectious Diseases (REIPI RD12/0015/0001).
Background and objectives Determination of cytomegalovirus (CMV) infection status, using CMV serology, in solid organ transplant (SOT) donors and recipients is essential to stratify the risk of post-transplant CMV disease, a significant cause of morbidity in SOT recipients [1,2]. Unfortunately, serology may be falsely positive due to passive antibodies from recent transfusion, which is common in the pre-transplant population. In situations where CMV serology may be unreliable, guidelines suggest assigning the highest risk donor/recipient CMV category, but this strategy may result in unnecessary anti-viral use and/or monitoring for CMV [1,2]. Alternative methods are needed to assign CMV infection status in SOT candidates with potential passive antibodies. Quantification of stimulation-induced CMV-specific CD4 + T-cells (CMV-TC), using flow cytometry, can reliably define CMV infection status in healthy adults and those awaiting renal transplant but has not been evaluated in other adult SOT candidates [3,4]. Previous studies have shown that CMV-TC have a unique “end-differentiated” T cell phenotype, characterized by the loss of expression of the co-stimulatory receptors CD27 and CD28 on CD4 + T-cells, thought to arise after repeated cycles of antigenic stimulation [, , , ]. Frequencies of CD27-CD28- CD4 + T-cells and stimulation-induced CMV-TC are highly correlated in healthy adults as well as those on hemodialysis and post-renal transplant, thus quantification of CD27-CD28- CD4 + T-cells may be a useful, rapid, stimulation-independent method of assigning CMV infection status in SOT candidates . Detection of CMV DNA in oropharyngeal secretions or urine with nucleic acid amplification testing (NAAT) is useful to confirm true positive CMV infection status in infant SOT candidates with potential passive maternal antibodies, but the utility of CMV NAAT in assigning CMV infection status in adults with potential passive antibodies is uncertain [10,11]. CMV shedding is much less common overall in adults than in young children but CMV shedding may be more common in ill adult SOT candidates. Thus, CMV NAAT may be a rapid and inexpensive way to confirm true CMV infection in CMV-seropositive adult SOT candidates with unreliable serology [12,13].