SummarySolid-phase assays (SPA) have facilitated detection and definition of antibodies to human leukocyte antigens (HLA) and major histocompatibility complex class I chain-related antigen A (MICA). However, clinical consequences of pretransplant SPA results in heart transplantation have been studied insufficiently in the current era of immunosuppression and rejection surveillance. Pretransplant sera, panelreactive antibodies (PRA), pretransplant crossmatch, and clinical data were retrospectively analyzed in 264 adult heart transplant recipients. The specificity of HLA and MICA antibodies and C1q-binding activity of donor-specific antibodies (DSA) were defined using SPA. Pretransplant HLA antibodies were detected in 57 (22%) individuals, in 28 individuals (11%); these antibodies were DSA after transplant. Preformed DSA and elevated peak PRA were independent predictors of pathologic AMR, which occurred in 19 individuals (7%). The increasing number of DSA and the cumulative mean fluorescence intensity of DSA were associated with AMR. C1q-binding assay was a suboptimal predictor of AMR in our cohort. Pretransplant allosensitization and MICA antibodies were related neither to impaired graft survival nor to other adverse clinical events during a median follow-up of 39 months. Identification of preformed DSA by SPA, in addition to PRA monitoring, may predict AMR in the contemporary era of heart transplantation.
Heart transplantation is a relatively common treatment for end‐stage heart failure. The major complication of heart transplantation is organ rejection. Epigenetic could play a role in the pathogenesis of organ rejection, and the FTO gene is a mediator of DNA methylation. We analyzed a tagging FTO SNP rs17817449 in both donor and recipient DNA obtained through 370 heart transplantations. Recipient FTO genotypes were not associated with either type of rejection or with the general increase in the risk of rejection. When compared with patients without a history of rejection, carriers of transplanted hearts with the FTO TT genotype exhibited a significantly increased risk (P = 0.02) of suffering from both types of rejection in comparison to carriers of hearts with at least one G allele (OR; 95% CI = 2.56; 1.15‐5.69). Our results suggest that the donor, but not the recipient, FTO genotype could be a significant predictor of acute rejection in heart transplant patients.
Background: Cytomegalovirus (CMV) is a major cause of infection in the early period after heart transplantation (HTx). There are limited data comparing universal prophylaxis with preemptive treatment of CMV infection in HTx recipients. Therefore, the goal of this study was to evaluate efficacy and safety of both strategies. Methods: A total of 17 HTx recipients were prospectively enrolled in the universal prophylaxis group. This study cohort was matched with 18 HTx recipients who had the same immunosuppressive regimen and received preemptive therapy for CMV infection. All patients were CMV-seropositive. The study group received oral valganciclovir in a dose of 900 mg daily for 100 days. The second group was treated in case of CMV viraemia higher than 500 copies/ml. The incidence of CMV infection, other opportunistic infections and acute graft rejection and adverse events were evaluated at 3 th , 6 th and 12 th months post-transplant. Results: Universal prophylaxis was well tolerated in 87.5% of the patients for a period of 100 days. Leukopenia was the most frequent side-effect that appeared in 25% of this group. This strategy decreased the rate of asymptomatic CMV infection during the first three months after HTx (11.7% vs 55.6%, p = 0.006) compared with preemptive therapy. This positive effect was associated with lower incidence of acute graft rejection at 12 months of follow up (6.3% vs 41.2%, p = 0.015).
Conclusion:Universal prophylaxis with valganciclovir in CMV-seropositive HTx recipients was acceptably safe and compared with preemptive therapy of CMV infection reduced the incidence of asymptomatic CMV infection and of acute graft rejection.
SOUHRNKontext: Cytomegalovirus (CMV) je jedním z hlavních původců infekce v časném pooperačním období po transplantaci srdce (OTS). V současnosti existují pouze omezená data srovnávající univerzální profylaxi s preemptivní terapií CMV infekce u pacientů po OTS. Cílem naší prospektivní studie bylo posoudit účinnost a bezpečnost obou metod. Metody: Do skupiny s univerzální profylaxí bylo zařazeno celkem 17 příjemců OTS. Kontrolní skupinu tvořilo 18 pacientů, kterým byla podána preemptivní terapie. Všichni pacienti měli zavedenou stejnou imunosupresivní léčbu a byli CMV sérologicky pozitivní. Za účelem univerzální profylaxe byl podán perorální valganciclovir v dávce 900 mg denně po dobu 100 dnů. Ve skupině s preemptivní terapií byla zahájena léčba
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