Role of HLA matching and donor specific antibody development in long-term survival, acute rejection and cardiac allograft vasculopathy.

Although there are different data supporting benefits of HLA matching in kidney transplantation, its role in heart transplantation is still unclear. HLA mismatch (MM) between donor and recipient can lead to the development of donor-specific antibodies (DSA) which produces negative events on the outcome of heart transplantation. Moreover, DSAs are involved in the development of antibody-mediated rejection (AMR) and are associated with an increase in cardiac allograft vasculopathy (CAV). In this study it is analyzed retrospectively the influence of HLA matching and anti-HLA antibodies on overall survival, AMR and CAV in heart transplantation. For this retrospective study are recruited heart transplanted patients at the Cardiac Transplantation Centre of Naples between 2000 and 2019. Among the 155 heart transplant patients, the mean number of HLA-A, B, -DR MM (0 to 6) between donor and recipient was 4.5 ± 1.1. The results show a negative association between MM HLA-DR and survival (p = 0.01). Comparison of patients with 0-1 MM at each locus to all others with 2 MM, for both HLA class I and class II, has not showed significant differences in the development of CAV. Our analysis detected DSA in 38.1% of patients. The production of de novo DSA reveals that there is not an influence on survival (p = 0.72) and/or AMR (p = 0.39). Instead, there is an association between the production of DSA class II and the probability of CAV development (p = 0.03). Mean fluorescence intensity (MFI) values were significantly higher in CAV-positive patients that CAV-negative patients (p = 0.02). Prospective studies are needed to evaluate HLA class II matching as an additional parameter for heart allocation, especially considering the increment of waiting list time.

Pan-yellow fever virus detection and lineage assignment by real-time RT-PCR and amplicon sequencing.

Yellow fever disease is a viral zoonosis that may result in a severe hemorrhagic disease. A safe and effective vaccine used in mass immunization campaigns has allowed control and mitigation against explosive outbreaks in endemic areas. Since the 1960's, re-emergent of the yellow fever virus has been observed. The timely implementation of control measures, to avoid or contain an ongoing outbreak requires rapid specific viral detection methods. Here a novel molecular assay, expected to detect all known yellow fever virus strains, is described. The method has demonstrated high sensitivity and specificity in real-time RT-PCR as well as in an endpoint RT-PCR set-up. Sequence alignment and phylogenetic analysis reveal that the amplicon resulting from the novel method covers a genomic region whose mutational profile is completely associated to the yellow fever viral lineages. Therefore, sequencing analysis of this amplicon allows for assignment of the viral lineage.