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  • In conclusion we demonstrated a significantly

    2020-07-28

    In conclusion, we demonstrated a significantly increased duration of CMV reactivation and a significantly increased incidence of CMV disease in CMV seropositive patients transplanted with a CMV seronegative donor (R+D−) compared to CMV seropositive patients transplanted with a CMV seropositive donor (R+D+) following TCD alloSCT, illustrating that despite alemtuzumab-based TCD, memory T-cells can be transferred from the graft to provide protective anti-viral immunity. Furthermore, we demonstrated that protective immunity against CMV was predominantly mediated by T-cells from recipient origin in patients transplanted with a CMV seronegative donor (R+D−) within the first year after TCD alloSCT, but that a primary donor-derived CMV-specific T-cell response was frequently observed within the first year following TCD alloSCT, even as early as 3 months following TCD alloSCT.
    Declarations of interest
    Introduction Cytomegalovirus (CMV) infection is considered the major cause of morbidity in solid organ transplant (SOT) recipients [1]. CMV is efficiently transmitted to recipients during transplantation and the risk of infection post transplantation increases in the absence of a pre-existing CMV specific immunity and with the amount of transplanted lymphoid tissue (being particularly high for lung and small intestine transplant) NHS-SS-Biotin receptor [2]. Additionally, long-term immunosuppression therapy, necessary to prevent graft rejection, poses an additional risk of CMV reactivation among recipients with previously acquired infection [2]. The pretransplant evaluation of donor and recipient serological status for CMV has been used as a marker of previous infection and as a risk factor for donor-derived transmission. It is assumed that patients with positive pretransplant CMV serology have also acquired a CMV-specific NHS-SS-Biotin receptor and the ability to control infection. Thus, although individual susceptibility to CMV infection is modulated by several factors (type of transplant, type of immunosuppression, or coinfection, among others), stratification according to the serological status D/R is the pillar of risk stratification. Consensus guidelines recommend that immunoglobulin G (IgG) anti-CMV antibody tests before SOT in both donors and recipients should be performed [1], [3]. The D/R serological combination differentiates between three main risk categories: (a) patients at high risk, when seronegative patients receive an organ from a seropositive donor (D+/R–); (b) patients at intermediate risk, seropositive recipients (R+); and (c) Patients at low risk, seronegative patients that receive an organ from a seronegative donor (D–/R–) [2], [4], [5]. The immune control of CMV replication in vivo is primarily driven by the T-cell-mediated response, a characteristic that has been proposed as a tool to individualize and therefore to optimize antiviral treatment [6], [7], and it has been associated with spontaneous clearance of CMV viraemia in patients at high (D+/R–) and intermediate risk (R+) [7], [8], [9], [10], [11], [12]. Although the majority of SOT patients are R+, this is precisely the least studied population and the few published reports include an insufficient sample size [13], [14]. R+ patients have a significant incidence of CMV DNAaemia (around 50%) and CMV disease (around 20%) after transplantation [15], [16]. We previously reported in Mena-Romo et al. [10] that having a positive T-cell immune response at 2 weeks and 4 weeks after transplantation independently reduced the risk of requiring early treatment and developing high-level viraemia. In that study, after a mid-term analysis and based on the unexpected high number of patients with no CMV-specific T-cell immune response at 2 weeks after transplantation, we initiated the study of the T-cell immune response before transplantation. However, the small number of patients with a pretransplant sample prevented a multivariate study to confirm if CMV-specific immunity was an independent protective factor for CMV disease [10]. Other authors reached only partial conclusions, and had little clinical utility since the CD8 T-cell response was characterized in small cohorts or with no stratification based on pretransplant serology, induction therapy or early treatment administration [17], [18], [19], [20].