Serum antibodies against mimotopes of Merkel cell polyomavirus oncoproteins detected by a novel immunoassay in healthy individuals and Merkel cell carcinoma patients.

Merkel cell polyomavirus (MCPyV) is the foremost causative factor of Merkel cell carcinoma (MCC), a rare yet highly aggressive skin cancer. Although the evaluation of circulating IgG antibodies against Merkel cell polyomavirus (MCPyV) LT/sT oncoproteins is clinically useful for MCC diagnosis/prognosis, a limited number of assays for identifying such antibodies have been developed. Herein, a novel indirect immunoassay with synthetic epitopes/mimotopes of MCPyV oncoproteins was computationally designed and experimentally validated on control sera and sera from healthy individuals and MCC patients.

Integration of Cellular and Humoral Immune Responses as an Immunomonitoring Tool for SARS-CoV-2 Vaccination in Healthy and Fragile Subjects.

Cellular and humoral immunity are both required for SARS-CoV-2 infection recovery and vaccine efficacy. The factors affecting mRNA vaccination-induced immune responses, in healthy and fragile subjects, are still under investigation. Thus, we monitored the vaccine-induced cellular and humoral immunity in healthy subjects and cancer patients after vaccination to define whether a different antibody titer reflected similar rates of cellular immune responses and if cancer has an impact on vaccination efficacy.

HIV-1 mutants expressing B cell clonogenic matrix protein p17 variants are increasing their prevalence worldwide.

AIDS-defining cancers declined after combined antiretroviral therapy (cART) introduction, but lymphomas are still elevated in HIV type 1 (HIV-1)-infected patients. In particular, non-Hodgkin's lymphomas (NHLs) represent the majority of all AIDS-defining cancers and are the most frequent cause of death in these patients. We have recently demonstrated that amino acid (aa) insertions at the HIV-1 matrix protein p17 COOH-terminal region cause protein destabilization, leading to conformational changes.

IgG antibodies against SARS-CoV-2 decay but persist 4 months after vaccination in a cohort of healthcare workers.

Background And Aims: Monitoring the immune response against SARS-CoV-2 is pivotal in the evaluation of long-term vaccine efficacy. Immunoglobulin G (IgG) antibodies represent an advisable tool to reach this goal, especially for the still poorly defined antibody trend induced by the new class of mRNA vaccines against SARS-CoV-2.

Materials And Methods: Anti-Spike RBD IgG antibodies were monitored in a cohort of healthcare workers at CRO Aviano, National Cancer Institute, through MAGLUMI® chemiluminescence assay, at 1 and 4 months after full-schedule of BNT162b2 or mRNA-1273 vaccination.

Biological Predictors of Tumors in Solid Organ Transplanted Patients During Oncological Surveillance: Potential Role of Circulating mRNA.

Background: tumors are a major cause of morbidity and mortality after long-term solid organ transplantation. Chronic immunosuppression strongly affects solid organ transplanted (SOT) patients' immune system by promoting immune evasion strategies and reactivations of viruses with oncogenic potential, ultimately leading to cancer onset. In this scenario, an oncological Surveillance Protocol integrated with biobanking of peripheral blood samples and evaluation of immunovirological and molecular parameters was activated for SOT patients at CRO-IRCCS Aviano, with the aim of identifying suitable biomarkers of cancer development.

Polymorphisms in Pepsinogen C and miRNA Genes Associate with High Serum Pepsinogen II in Gastric Cancer Patients.

Background: Pepsinogen (PG) II (PGII) is a serological marker used to estimate the risk of gastric cancer but how PGII expression is regulated is largely unknown. It has been suggested that PGII expression, from the (Progastricsin) gene, is regulated by microRNAs (miRNA), but how PGII levels vary with infection and miRNAs genotype remains unclear.

Methods: Serum levels of PGI and PGII were determined in 80 patients with gastric cancer and persons at risk for gastric cancer (74 first-degree relatives of patients, 62 patients with autoimmune chronic atrophic gastritis, and 2 patients with dysplasia), with and without infection.

Overview of Epstein-Barr-Virus-Associated Gastric Cancer Correlated with Prognostic Classification and Development of Therapeutic Options.

Gastric cancer (GC) is a deadly disease with poor prognosis that is characterized by heterogeneity. New classifications based on histologic features, genotypes, and molecular phenotypes, for example, the Cancer Genome Atlas subtypes and those by the Asian Cancer Research Group, help understand the carcinogenic differences in GC and have led to the identification of an Epstein-Barr virus (EBV)-related GC subtype (EBVaGC), providing new indications for tailored treatment and prognostic factors. This article provides a review of the features of EBVaGC and an update on the latest insights from EBV-related research with a particular focus on the strict interaction between EBV infection and the gastric tumor environment, including the host immune response.

PDCD1 and IFNL4 genetic variants and risk of developing hepatitis C virus-related diseases.

Background: Genetic variants of IFNL4 and PDCD1 genes have been shown to influence the spontaneous clearance of hepatitis C virus (HCV) infection. We investigated the IFNL4 rs12979860 and the PDCD1 polymorphisms in 734 HCV-positive patients, including 461 cases with liver disease of varying severity and 273 patients with lymphoproliferative disorders to determine the association of these genes with patient's outcome.

Methods: Expression levels of PDCD1 mRNA encoded by haplotypes were investigated by quantitative PCR in hepatocellular carcinoma (HCC) tissue and peripheral blood mononuclear cells.

Differential Plasticity in the Gastric Niche of Subjects at Increased Gastric Cancer Risk.

() represents an independent risk factor for Gastric Cancer (GC). First Degree Relatives (FDR) of GC subjects and Autoimmune Gastritis (AG) patients are both at increased risk for GC. genetic heterogeneity within the gastric niche of FDR and AG individuals has been little explored.

Polymorphism in Toll-Like Receptors and Motility in Autoimmune Atrophic Gastritis and Gastric Cancer.

Autoimmune atrophic gastritis (AAG) is associated with an increased risk of certain types of gastric cancer (GC). () infection may have a role in the induction and/or maintenance of AAG and GC. Toll-like receptors (TLR) are essential for recognition and subsequent innate and adaptive immunity responses.

Protein signature characterizing strains of patients with autoimmune atrophic gastritis, duodenal ulcer and gastric cancer.

Background: () represents a key factor in the etiology of autoimmune atrophic gastritis (AAG), duodenal ulcer (DU) and gastric cancer (GC). The aim of this study was to characterize the differential protein expression of isolated from gastric biopsies of patients affected by either AAG, DU or GC.

Methods: The strains were isolated from endoscopic biopsies from the stomach of patients with gastric disease.

In-depth analysis of compartmentalization of HIV-1 matrix protein p17 in PBMC and plasma.

HIV-1 p17 plays an important role in the virus life-cycle and disease pathogenesis. Recent studies indicated a high heterogeneity of p17. A high number of insertions in the p17 carboxy-terminal region have been more frequently detected in patients with non-Hodgkin lymphoma (NHL), suggesting a role of altered p17 in lymphomagenesis.

First external quality assurance program of the Italian HLA-B*57:01 Network assessing the performance of clinical virology laboratories in HLA-B*57:01 testing.

Background: Since the HLA-B*57:01 allele is strongly associated with abacavir hypersensitivity reaction, testing for the presence of HLA-B*57:01 is mandatory before administration of abacavir. While HLA-B*57:01 testing is usually provided by pharmacogenetics, genetics or blood transfusion services, clinical virology laboratories can be an optimal opportunity for HLA-B*57:01 testing since they receive blood samples for routine HIV monitoring and have the expertise for convenient and less expensive PCR-based point mutation assays.

Objectives: The Italian HLA-B*57:01 Network gathers accredited clinical virology laboratories offering HLA-B*57:01 testing in Italy with the aim to share protocols, test new methods, develop and maintain external quality assurance (EQA) programs.

Postautologous stem cell transplantation long-term outcomes in 26 HIV-positive patients affected by relapsed/refractory lymphoma.

Objectives: To describe survival data, CD4 T-cell long-term dynamics and the correlation between dynamics and events occurrence in 26 HIV-positive patients with refractory lymphoma in complete response after autologous stem cell transplantation (ASCT).

Design: Retrospective single-centre study.

Methods: Lymphoma relapse, second cancers and opportunistic infections were considered after ASCT.

γ-Herpesvirus load as surrogate marker of early death in HIV-1 lymphoma patients submitted to high dose chemotherapy and autologous peripheral blood stem cell transplantation.

Autologous stem cell transplantation (ASCT) is a feasible procedure for human immunodeficiency virus-1 (HIV-1) lymphoma patients, whose underlying disease and intrinsic HIV-1- and ASCT-associated immunodeficiency might increase the risk for γ-herpesvirus load persistence and/or reactivation. We evaluated this hypothesis by investigating the levels of Epstein-Barr virus (EBV)- and Kaposi sarcoma-associated herpesvirus (KSHV)-DNA levels in the peripheral blood of 22 HIV-1-associated lymphoma patients during ASCT, highlighting their relationship with γ-herpesvirus lymphoma status, immunological parameters, and clinical events. EBV-DNA was detected in the pre-treatment plasma and peripheral blood mononuclear cells (PBMCs) of 12 (median 12,135 copies/mL) and 18 patients (median 417 copies/10(6) PBMCs), respectively; the values in the two compartments were correlated (r = 0.

Autograft HIV-DNA load predicts HIV-1 peripheral reservoir after stem cell transplantation for AIDS-related lymphoma patients.

Autologous stem cell transplantation (ASCT) is a widely used procedure for AIDS-related lymphomas, and it represents an opportunity to evaluate strategies curing HIV-1 infection. The association of autograft HIV-DNA load with peripheral blood HIV-1 reservoir before ASCT and its contribution in predicting HIV-1 reservoir size and stability during combination antiretroviral therapy (cART) after transplantation are unknown. Aiming to obtain information suggesting new functional cure strategies by ASCT, we retrospectively evaluated HIV-DNA load in autograft and in peripheral blood before and after transplantation in 13 cART-treated HIV-1 relapse/refractoring lymphoma patients.

Which tools may help physicians in female fertility prediction after autologous bone marrow transplantation for lymphoma? A pilot study.

Objective(s): The report of our experience on fertility preservation and the validation of some tools useful to predict fertility in young females who underwent haematopoietic cell transplantation for their lymphoma.

Study Design: A retrospective study involving 17 consecutive women of child-bearing age affected by lymphoma and submitted to haematopoietic cell transplantation in our centre.

Results: We described a high rate of parenthood in our patient series: 5 out of 17 (29%) patients became pregnant and 1 out of 5 had two pregnancies.

Differential proteomics of Helicobacter pylori associated with autoimmune atrophic gastritis.

Atrophic autoimmune gastritis (AAG) is a condition of chronic inflammation and atrophy of stomach mucosa, for which development can be partially triggered by the bacterial pathogen Helicobacter pylori (HP). HP can cause a variety of gastric diseases, such as duodenal ulcer (DU) or gastric cancer (GC). In this study, a comparative proteomic approach was used by two-dimensional fluorescence difference gel electrophoresis (DIGE) to identify differentially expressed proteins of HP strains isolated from patients with AAG, to identify markers of HP strain associated with AAG.

Identification and characterization of CDH1 germline variants in sporadic gastric cancer patients and in individuals at risk of gastric cancer.

Objective: To screen and characterize germline variants for E-cadherin (CDH1) in non-hereditary gastric cancer (GC) patients and in subjects at risk of GC.

Methods: 59 GCs, 59 first degree relatives (FDRs) of GC, 20 autoimmune metaplastic atrophic gastritis (AMAGs) and 52 blood donors (BDs) were analyzed for CDH1 by direct sequencing, structural modelling and bioinformatics. Functional impact on splicing was assessed for intronic mutations.

Cancer, aging and immune reconstitution.

Aging is a complex phenomenon involving multiple physiological functions. Among these, very important are the modifications induced in the immune system; these modifications may be related to cancer development, a disease of older people. We herein describe the age-dependent alterations observed in the various arms of the immune system.

Multiplex analysis of blood cytokines as a prognostic tool in HIV related non-Hodgkin lymphoma patients: a potential role of interleukin-7.

Background: Recent studies suggest a powerful prognostic value for blood cytokine levels in different diseases. Non-Hodgkin lymphoma (NHL) still represents one of the main causes of death in the HIV setting, with a wide variation in outcome and survival among patients. We measured blood concentrations of 11 cytokines from HIV-NHL patients at diagnosis and correlated these with the patient outcome to evaluate the prognostic value.

Assessment of immunovirological features in HIV related non-Hodgkin lymphoma patients and their impact on outcome.

Background: Despite the era of highly active antiretroviral therapy, non-Hodgkin lymphoma (NHL) remains one of the main causes of death in HIV-infected patients, with a wide variation on the outcome.

Objectives: We investigated immunological status and EBV, HHV8, HIV viral load in a group of HIV-infected patients at diagnosis of NHL to evaluate their prognostic significance.

Study Design: Eighty-one consecutive HIV+ NHL patients were studied.

Multicenter comparative study of Epstein-Barr virus DNA quantification for virological monitoring in transplanted patients.

Background: EBV-related post-transplant lymphoproliferative diseases are usually accompanied by increased EBV DNA in peripheral blood. Monitoring EBV DNAemia is the basis for weighing decisions regarding initiation of pre-emptive or anti-EBV-related tumor therapy. However, the definition of clinically relevant cut-off values is hampered by the lack of standardization in EBV DNA testing.

Immune recovery after autologous stem cell transplantation is not different for HIV-infected versus HIV-uninfected patients with relapsed or refractory lymphoma.

Background: High-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) are feasible and effective salvage treatments for human immunodeficiency virus (HIV)-related relapse or refractory lymphoma. Among the main concerns with ASCT in HIV-infected persons is the additional immune depletion caused by treatment, which could amplify the preexisting immune deficit. The aims of our study were to assess the impact of conventional chemotherapy before salvage treatment was administered, in this population, and to evaluate immune reconstitution dynamics during ASCT.