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American Journal of Blood Research (1)
Journal of Clinical Microbiology (1)
PLoS Pathogens (1)
Mele, Alfonso (3)
Spada, Enea (3)
Accapezzato, Daniele (1)
Barnaba, Vincenzo (1)
Caserta, Carmelo Antonio (1)
De Fusco, Carmela (1)
Del Porto, Paola (1)
Franceschini, Debora (1)
Garbuglia, Anna Rosa (1)
Marcucci, Fabrizio (1)
Morrone, Stefania (1)
Paroli, Marino (1)
Piccolella, Enza (1)
Piconese, Silvia (1)
Poggi, Vincenzo (1)
Pulsoni, Alessandro (1)
Sagliocca, Luciano (1)
Sette, Alessandro (1)
Sidney, John (1)
Sourdis, John (1)
Trella, Emanuele (1)
Walker, Christopher M. (1)
Year of Publication
Polyfunctional Type-1, -2, and -17 CD8+ T Cell Responses to Apoptotic Self-Antigens Correlate with the Chronic Evolution of Hepatitis C Virus Infection
Del Porto, Paola
Walker, Christopher M.
Caspase-dependent cleavage of antigens associated with apoptotic cells plays a prominent role in the generation of CD8+ T cell responses in various infectious diseases. We found that the emergence of a large population of autoreactive CD8+ T effector cells specific for apoptotic T cell-associated self-epitopes exceeds the antiviral responses in patients with acute hepatitis C virus infection. Importantly, they endow mixed polyfunctional type-1, type-2 and type-17 responses and correlate with the chronic progression of infection. This evolution is related to the selection of autoreactive CD8+ T cells with higher T cell receptor avidity, whereas those with lower avidity undergo prompt contraction in patients who clear infection. These findings demonstrate a previously undescribed strict link between the emergence of high frequencies of mixed autoreactive CD8+ T cells producing a broad array of cytokines (IFN-γ, IL-17, IL-4, IL-2…) and the progression toward chronic disease in a human model of acute infection.
The emergence of a large population of mixed polyfunctional (type-1, -2, -17) CD8+ T cell effector responses specific for apoptotic T cell-associated self-epitopes rather than the dysfunction or altered quality of virus-specific CD8+ T cells is associated with the progression toward chronic disease in the human model of acute HCV infection. The chronic evolution is associated with the selection of autoreactive CD8+ T cells with higher T cell receptor avidity, whereas those with lower avidity undergo prompt contraction, as seen in patients undergoing infection resolution. We suggest that these autoreactive responses are secondary to the viral persistence and can participate to the HCV-related immunopathology. This data has implications for the prognosis and therapy of infections undergoing chronic evolution.
The association of hepatitis B virus infection with B-cell non-Hodgkin lymphoma – a review
Caserta, Carmelo Antonio
American Journal of Blood Research
Epidemiological studies performed over the last decade have demonstrated a positive association between persistent, hepatitis B surface antigen (HBsAg)-positive hepatitis B virus (HBV) infection and B-cell non-Hodgkin lymphoma (NHL), with HBV-infected patients having a 2-3-fold higher risk to develop NHL than non-infected patients. Moreover, there is evidence that also occult HBV infection (HBsAg-negative, HBV DNA-positive) associates with NHL. An association with HBV infection may exist also for other hematological malignancies, but available evidence is much less persuasive than for NHL. In this review article we will discuss available results on the association between HBsAg-positive HBV infection and NHL, as well as the significance of other serological markers of HBV infection in these subjects. We will also discuss the possible etiopathogenic role of HBV, and propose a multifactorial model for lymphomagenesis. Experimental evidence for multifactorial etiopathogenesis has been obtained in recent years for HBV-associated hepatocellular carcinoma (HCC), and we suggest that a similar model may apply to HBV-associated lymphoma as well. Eventually, we will also address some unresolved questions. Two of these are of particular relevance. First, do HBV-positive NHL patients show regression of their hematologic malignancy upon antiviral therapy? A positive answer would represent a direct demonstration of the necessary etiological role of the virus in the development of NHL, as has been shown previously for HCV-associated lymphomas. Second, if HBV plays a necessary role in lymphomagenesis, then expansion of HBV vaccination is expected to reduce the number of incident NHL cases, even though this effect might become evident only after a long time interval. Studies in those countries which have introduced universal HBV vaccination about two decades ago, like Italy, may soon provide results on this important point.
Hepatitis B virus; occult infection; anti-HBs antibodies; anti-HBe antibodies; anti-HBc antibodies; non-Hodgkin lymphoma; hematologic malignancies; antiviral therapy; multicausal etiology; vaccination
Use of the Minimum Spanning Tree Model for Molecular Epidemiological Investigation of a Nosocomial Outbreak of Hepatitis C Virus Infection
Garbuglia, Anna Rosa
De Fusco, Carmela
Journal of Clinical Microbiology
The minimum spanning tree (MST) model was applied to identify the history of transmission of hepatitis C virus (HCV) infection in an outbreak involving five children attending a pediatric oncology-hematology outpatient ward between 1992 and 2000. We collected blood samples from all children attending since 1992, all household contacts, and one health care worker positive for antibody to HCV (anti-HCV). HCV RNA detection was performed with these samples and with smears of routinely collected bone marrow samples. For all isolates, we performed sequence analysis and phylogenetic tree analysis of hypervariable region 1 of the E2 gene. The MST model was applied to clinical-epidemiological and molecular data. No additional cases were detected. All children, but not the health care worker, showed genotype 3a. On six occasions, all but one child had shared the medication room with another patient who later seroconverted. HCV RNA detection in bone marrow smears revealed, in some cases, a delay of several months in anti-HCV responses. Sequence analysis and phylogenetic tree analysis revealed a high identity among the isolates. The MST model applied to molecular data, together with the clinical-epidemiological data, allowed us to identify the source of the outbreak and the most probable patient-to-patient chain of transmission. The management of central venous catheters was suspected to be the probable route of transmission. In conclusion, the MST model, supported by an exhaustive clinical-epidemiological investigation, appears to be a useful tool in tracing the history of transmission in outbreaks of HCV infection.
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