Publications by authors named "Maria Raffaella Petrara"

In this work our aim was to identify early biomarkers in plasma samples associated with mortality in children with perinatal HIV treated early in life, to potentially inform early intervention targeting this vulnerable group. 20/215 children (9.3%) with perinatal HIV, enrolled within 3 months of age died prematurely within the first year of the study, despite early ART initiation.

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Article Synopsis
  • Despite ongoing antiretroviral therapy, many adolescents and young adults with perinatally acquired HIV are experiencing signs of premature aging and associated health issues, leading to the necessity of studying aging biomarkers and their link to the HIV reservoir.* -
  • A study involving 55 adolescents and young adults showed they had higher rates of certain activated immune cells and inflammatory markers compared to healthy peers, alongside shorter telomeres, indicating faster aging processes.* -
  • The participants were categorized based on their viral suppression status, revealing that those who started ART early (Early Suppressed) had fewer signs of aging and inflammation compared to those who started later, stressing the critical role of early treatment in improving health outcomes.*
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Background And Objectives: mRNA vaccines elicit a durable humoral response to SARS-CoV-2 in adults, whereas evidence in children is scarce. This study aimed to assess the early and long-term immune response to the mRNA vaccine in children with or without previous SARS-CoV-2 infection.

Methods: In a multicentre prospective observational study, we profiled the immune response to the Pfizer BioNTech (BNT162b2) vaccine in 5-11-year-old children attending the University Pediatric Hospital of Padua and Bambino-Gesù Hospital in Rome (Italy) from December-2021 to February-2023.

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Importance: Understanding the long-term immune response against SARS-CoV-2 infection in children is crucial to optimize vaccination strategies. Although it is known that SARS-CoV-2 antibodies may persist in adults 12 months after infection, data are limited in the pediatric population.

Objective: To examine long-term anti-SARS-CoV-2 spike receptor-binding domain (S-RBD) IgG kinetics in children after SARS-CoV-2 infection.

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Liver transplanted (LT) patients for hepatocellular carcinoma (LT-HCC) or for other causes (LT-no-HCC) may develop post-transplantation malignancies. Although immune activation and senescence are frequently implicated in cancer development, no data is available on their possible role as biomarkers predictive of tumor onset in this setting. A total of 116 patients were investigated: the 45 LT-HCC patients were older than the 71 LT-non-HCC (p=0.

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Introduction: Persistence of HIV-1, causing chronic immune activation, is a key determinant of premature senescence. Early antiretroviral therapy (ART) has been associated with a reduced HIV-1 reservoir in children with perinatally acquired HIV-1 (PHIV), but its impact on the senescence process is an open question. We investigated the association between HIV-1 reservoir and biological and immune ageing profile in PHIV enrolled in the multicentre cross-sectional study CARMA (Child and Adolescent Reservoir Measurements on early suppressive ART) conducted within the EPIICAL (Early treated Perinatally HIV Infected individuals: Improving Children's Actual Life) consortium.

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Background: The immune response plays a pivotal role in dictating the clinical outcome in severe acute respiratory syndrome coronavirus 2 (SARSCoV2)-infected adults, but it is still poorly investigated in the pediatric population.

Methods: Of 209 enrolled subjects, 155 patients were confirmed by PCR and/or serology as having coronavirus disease 2019 (COVID-19). Blood samples were obtained at a median of 2.

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Background: Although SARS-CoV-2 immunizations have started in most countries, children are not currently included in the vaccination programs; thus, it remains crucial to define their anti-SARS-CoV-2 immune response in order to minimize the risk for other epidemic waves. This study sought to provide a description of the virology ad anti-SARS-CoV-2 immunity in children with distinct symptomatology.

Methods: Between March and July 2020, we recruited 15 SARS-CoV-2 asymptomatic (AS) and 51 symptomatic (SY) children, stratified according to WHO clinical classification.

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Background: Recent evidence suggests that neutralizing antibodies (nAbs) to severe acute respiratory syndrome coronavirus 2 may persist over time; however, knowledge regarding pediatric subjects is limited.

Methods: A single-center, prospective observational study was conducted on 57 family clusters of coronavirus disease 2019, including children of neonatal and pediatric age attending the University Hospital of Padua (Italy). For each patient, blood samples were collected for both the quantification of nAbs through a plaque reduction neutralizing test and the detection of antinucleocapsid-spike protein immunoglobulin G and/or immunoglobulin M.

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As the global COVID-19 pandemic progresses, it is paramount to gain knowledge on adaptive immunity to SARS-CoV-2 in children to define immune correlates of protection upon immunization or infection. We analyzed anti-SARS-CoV-2 antibodies and their neutralizing activity (PRNT) in 66 COVID-19-infected children at 7 (±2) days after symptom onset. Individuals with specific humoral responses presented faster virus clearance and lower viral load associated with a reduced in vitro infectivity.

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Besides its canonical role in stabilizing telomeres, telomerase reverse transcriptase (TERT) may promote tumor growth/progression through extra-telomeric functions. Our previous in vitro studies demonstrated that short-term TERT inhibition by BIBR1532 (BIBR), an inhibitor of TERT catalytic activity, negatively impacts cell proliferation and viability via telomeres' length-independent mechanism. Here we evaluate the anti-proliferative and pro-apoptotic effects of short-term telomerase inhibition in vivo in wild-type (wt) and mutant (; ) zebrafish embryos, and in malignant human B cells xenografted in casper zebrafish embryos.

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Chronic HIV-infected children suffer from premature aging and aging-related diseases. Viral replication induces an ongoing inflammation process, with the release of pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), the activation of the immune system, and the production of proinflammatory cytokines. Although combined highly active antiretroviral therapy (ART) has significantly modified the natural course of HIV infection, normalization of T and B cell phenotype is not completely achievable; thus, many HIV-infected children display several phenotypical alterations, including higher percentages of activated cells, that favor an accelerated telomere attrition, and higher percentages of exhausted and senescent cells.

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Post-transplant lymphoproliferative disorders (PTLD) represent a severe complication in transplanted patients and Epstein-Barr Virus (EBV) is the main driver. Besides immunodepression, immune activation/chronic inflammation play an important role in both virus reactivation and expansion of EBV-positive B cells. The aim of this study was to assess the impact of immunosuppressive strategies on factors involved in the PTLD's pathogenesis.

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In our previous study, we found that low thymic output and short telomere length were associated with a higher risk of tumor in elderly cancer patients. Here, we aimed to examine in depth the impact of immunological and biological senescence and immune activation on disease outcome in elderly patients with colorectal cancer (CRC).Peripheral blood samples from 81 CRC patients were studied for immune activation, immune senescence and recent thymic emigrant(RTE) CD4 and CD8 cells by flow cytometry.

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Background: Premature aging and related diseases have been documented in HIV-infected adults. Data are now emerging also regarding accelerated aging process in HIV-infected children.

Methods: A narrative review was performed searching studies on PubMed published in English language in 2004-2017, using appropriate key words, including "aging", "children", "HIV", "AIDS", "immunosenescence", "pathogenesis", "clinical conditions".

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The Epstein-Barr virus (EBV) is a ubiquitous human γ-herpesvirus causally linked to a broad spectrum of both lymphoid and epithelial malignancies. In order to maintain its persistence in host cells and promote tumorigenesis, EBV must restrict its lytic cycle, which would ultimately lead to cell death, selectively express latent viral proteins, and establish an unlimited proliferative potential. The latter step depends on the maintenance of telomere length provided by telomerase.

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Objectives: Although monotherapy (mART) effectiveness in maintaining viral suppression and CD4 cell count has been extensively examined in HIV-1-infected patients, its impact on HIV-1 reservoir, immune activation, microbial translocation and co-infection with Epstein-Barr Virus (EBV) is unclear.

Methods: This retrospective study involved 32 patients who switched to mART; patients were studied at baseline, 48 and 96 weeks after mART initiation. Thirty-two patients who continued combined antiretroviral therapy (cART) over the same period of time were included in the study.

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Objective: Several pieces of evidence indicate that HIV-infected adults undergo premature aging. The effect of HIV and antiretroviral therapy (ART) exposure on the aging process of HIV-infected children may be more deleterious since their immune system coevolves from birth with HIV.

Design: Seventy-one HIV-infected (HIV+), 65 HIV-exposed-uninfected (HEU), and 56 HIV-unexposed-uninfected (HUU) children, all aged 0-5 years, were studied for biological aging and immune senescence.

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Post-transplant lymphoproliferative disorders (PTLDs) represent the most severe complication of both solid organ and hematopoietic stem cell transplantation. The Epstein-Barr Virus (EBV) is the main driver of PTLD, particularly those occurring early after transplantation. EBV-driven malignancies are associated with selective expression of latent viral proteins, but uncontrolled lytic replication may favor early phases of cell transformation.

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Correlations between clinical/immunological treatment failure and viral load (VL) detected by dried blood spot (DBS) sampling were explored in HIV-1-infected children in Uganda. Of 104 children on combined antiretroviral treatment (cART), 12.5% experienced clinical and/or immunological failure, while 28.

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Background: Epstein-Barr Virus (EBV) is involved in a wide range of malignancies, particularly in immunocompromised subjects. In Africa, EBV primary infection occurs during early childhood, but little is known about the EBV load in Human Immunodeficiency Virus type 1 (HIV-1)-infected children.

Methods: Blood samples from 213 HIV-1-infected children, 140 of whom were receiving antiretroviral therapy (ART), were collected at the Nsambya Hospital in Kampala, Uganda, and obtained for dried blood spot analysis.

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Highly active antiretroviral therapy (HAART) changed the natural history of pediatric HIV infection. This review focuses on trends of HIV-associated cancers in childhood in the HAART era and analyses potential pathogenetic mechanisms. HAART reduced AIDS-defined-malignancies (ADM), but incidence of several non-ADM is increasing.

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Molecular methods are important tools for diagnosis and monitoring of many lymphoproliferative disorders. The reliability of lymphoma diagnoses is strikingly different between developed and developing countries, partly due to lack of access to these advanced molecular analyses. To overcome these problems, we propose a new application of dried blood spots (DBS) for detecting clonal B-cell populations in peripheral blood (PB).

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Background: Non-Hodgkin's Lymphomas (NHL) are common in African children, with endemic Burkitt's lymphoma (BL) being the most common subtype. While the role of Epstein-Barr Virus (EBV) in endemic BL is known, no data are available about clinical presentations of NHL subtypes and their relationship to Human Immunodeficiency Virus (HIV) infection and Epstein Barr Virus (EBV) load in peripheral blood of children in north-western, Tanzania.

Methods: A matched case control study of NHL subtypes was performed in children under 15 years of age and their respective controls admitted to Bugando Medical Centre, Sengerema and Shirati district designated hospitals in north-western, Tanzania, between September 2010 and April 2011.

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