Background/Aims: Hepatitis C virus (HCV) infection results in a high frequency of chronic disease. The aim of this study was to identify early prognostic markers of disease resolution by performing a comprehensive analysis of viral and host factors during the natural course of acute HCV infection. Methods: The clinical course of acute hepatitis C was determined in 34 consecutive patients. Epidemiological and virological parameters, as well as cell mediated immunity (CMI) and distribution of human leukocyte antigens (HLA) alleles were analysed. Results: Ten out of 34 patients experienced self-limiting infection, with most resolving patients showing fast kinetics of viral clearance: at least one negative HCV RNA test during this phase predicted a favourable outcome. Among other clinical epidemiological parameters measured, the self-limiting course was significantly associated with higher median peak bilirubin levels at the onset of disease, and with the female sex, but only the latter parameter was independently associated after multivariate analysis. No significant differences between self-limiting or chronic course were observed for the distribution of DRB1 and DQB1 alleles. HCV specific T cell response was more frequently detected during acute HCV infection, than in patients with chronic HCV disease. A significantly broader T cell response was found in patients with self-limiting infection than in those with chronic evolving acute hepatitis C. Conclusion:The results suggest that host related factors, in particular sex and CMI, play a crucial role in the spontaneous clearance of this virus. Most importantly, a negative HCV RNA test and broad CMI within the first month after onset of the symptoms represent very efficacious predictors of viral clearance and could thus be used as criteria in selecting candidates for early antiviral treatment.

Platelet transfusions, main therapy of Glanzmann Thromboasthenia (GT), can induce an allo-immunization against human leucocyte antigen and integrin alphaIIbbeta3. We have investigated in our GT patients the rate of allo-immunization and of refractoriness to platelet transfusions. From 1975 until December 2005, we have followed 17 GT patients: 14 type 1, 3 variant type; nine females, eight males; median age at diagnosis 9.8 years (range 1-44.5); median age at the time of the study 35.5 years (range 23.6-68.5). In our patients, 121 bleeding episodes occurred (24 severe, 37 moderate, and 60 mild). Ten major and 22 minor surgical procedures have been performed. Two spontaneous deliveries and three caesarian sections with five live births were performed; moreover, one late foetal loss occurred, and one voluntary abortion was performed. Sixteen of 17 patients have been transfused at least once in life with platelets and/or red blood cells (RBC). All transfused patients have been investigated for the presence of anti-HLA and anti-integrin alphaIIbbeta3 allo-antibodies. The positiveness of allo-antibodies has been demonstrated in 4/16 transfused patients (25%): isolated for anti-HLA in two; isolated for anti-integrin alphaIIbbeta3 in one; and combined in one. In spite of the presence of allo-antibodies, platelet transfusions have always been effective and the haemostasis was not compromised.

In this study serologic records of 100 children with confirmed AIHA are reported. This series, much larger than any previously reported, is critically reviewed and analyzed to delineate the immunologic features of the disease in childhood.

Our data provide evidence of strong and multispecific T cell responses with a sustained ability to proliferate in response to antigen stimulation as reliable pharmacodynamic measures of a protective CMI during acute infection, and suggest that early impairment of proliferation may contribute to loss of T cell response and chronic HCV persistence.

Cellular immune responses are crucial for the control of EBV-associated lymphoproliferative diseases. To induce an anti-EBV cell-mediated immunity, we have used dendritic cells (DCs) generated by a 3-day culture of human CD14+ monocytes in the presence of GM-CSF and type I IFN (IFN-DCs) and pulsed with peptides corresponding to CTL EBV epitopes. The functional activity of IFN-DCs was compared with that of APCs differentiated by culturing monocytes for 3 days with GM-CSF and IL-4 and indicated as IL-4-DCs. Stimulation of PBLs from EBV-seropositive donors with EBV peptide-pulsed autologous IFN-DCs resulted in a stronger expansion of specific T lymphocytes producing IFN-γ with respect to stimulation with peptide-loaded IL-4-DCs, as assessed by ELISPOT assays. When purified CD8+ T cells were cocultured with EBV peptide-pulsed IFN-DCs or IL-4-DCs, significantly higher levels of specific cytotoxic activity were observed in CD8+ T cell cultures stimulated with IFN-DCs. Injection of peptide-pulsed IFN-DCs into SCID mice transplanted with autologous PBLs led to the recovery of a significantly greater number of EBV-specific human CD8+ T cells from the spleen and the peritoneal cavity with respect to that recovered from mice injected with peptide-pulsed IL-4-DCs. Moreover, a significant delay in lymphoma development was observed when peptide-pulsed IFN-DCs were injected into SCID mice reconstituted with PBMCs endowed with a high capability of lymphoma induction, whereas injection of unpulsed IFN-DCs was ineffective. Our results indicate that IFN-DCs efficiently promote in vitro and in vivo the expansion of CD8+ T lymphocytes acting as cytotoxic effectors against EBV-transformed cells.

Solid organ transplant patients are at a higher risk for poor CoronaVirus Disease‐2019 (COVID‐19)‐related outcomes and have been included as a priority group in the vaccination strategy worldwide. We assessed the safety and efficacy of a two‐dose vaccination cycle with mRNA‐based COVID‐19 vaccine (BNT162b2) among 82 kidney transplant outpatients followed in our center in Rome, Italy. After a median of 43 post‐vaccine days, a SARS‐CoV‐2 anti‐Spike seroprevalence of 52.4% (n = 43/82) was observed. No impact of the vaccination on antibody‐mediated rejection or graft function was observed, and no significant safety concerns were reported. Moreover, no de novo HLA‐donor‐specific antibodies (DSA) were detected during the follow‐up period. Only one patient with pre‐vaccination HLA‐DSA did not experience an increased intensity of the existing HLA‐DSA. During the follow‐up, only one infection (mild COVID‐19) was observed in a patient after receiving the first vaccine dose. According to the multivariable logistic regression analysis, lack of seroconversion after two‐dose vaccination independently associated with patient age ≥60 years (OR = 4.50; P = .02) and use of anti‐metabolite as an immunosuppressant drug (OR = 5.26; P = .004). Among younger patients not taking anti‐metabolites, the seroconversion rate was high (92.9%). Further larger studies are needed to assess the best COVID‐19 vaccination strategy in transplanted patients.

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Cellular immune responses are induced during hepatitis C virus (HCV) infection and acute-phase CD8 + T cells are supposed to play an important role in controlling viral replication. In chimpanzees, failure of CD8 + T cells to control HCV replication has been associated with acquisition of mutations in MHC class I-restricted epitopes. In humans, although selection of escape mutations in an immunodominant CTL epitope has been recently described, the overall impact of immune escape during acute HCV infection is unclear. Here, by performing an in depth analysis of the relationship between early cellular immune responses and viral evolution in a chronically evolving HCV acutely infected individual, we demonstrate: (i) the presence of a potent and focused CD8 + T cell response against a novel epitope in the NS3 protein, (ii) the elimination of the quasispecies harboring the original amino acid sequence within this epitope, and (iii) the selection for a virus population bearing amino acid changes at a single residue within the cytotoxic T cell epitope that strongly diminished T cell recognition. These results support the view that acute-phase CD8 + T cell responses exert a biologically relevant pressure on HCV replication and that viruses escaping this host response could have a significant survival advantage.