Splenomegaly in CVID patients associates with CMV replication and alterations of immune cells and functions.

Background: Splenomegaly represents a frequent non-infectious manifestation in Common Variable Immunodeficiency (CVID) and associates with specific clinical and immunophenotypic characteristics.

Objective: To investigate the association between splenomegaly, infections, and immunophenotype in CVID patients.

Methods: A cohort of 32 CVID patients (13 with splenomegaly) was enrolled.

Butyrate enhances CD56 NK cell-driven killing of activated T cells and modulates NK cell chromatin accessibility.

Gut bacteria-derived metabolites, such as butyrate (BUT), induce T regulatory cells through inhibition of histone deacetylases (HDAC). Natural killer (NK) cells are innate lymphocytes with important effector and regulatory functions; little is known on the effect of BUT on NK cells. Here we aimed at evaluating whether BUT affects the epigenetic landscape of human NK cells.

Evaluation of Frequency of CMV Replication and Disease Complications Reveals New Cellular Defects and a Time Dependent Pattern in CVID Patients.

Purpose: Common Variable Immunodeficiency (CVID) is characterized by hypogammaglobulinemia and failure of specific antibody production due to B-cell defects. However, studies have documented various T-cell abnormalities, potentially linked to viral complications. The frequency of Cytomegalovirus (CMV) replication in CVID cohorts is poorly studied.

Multiscale networks in multiple sclerosis.

Complex diseases such as Multiple Sclerosis (MS) cover a wide range of biological scales, from genes and proteins to cells and tissues, up to the full organism. In fact, any phenotype for an organism is dictated by the interplay among these scales. We conducted a multilayer network analysis and deep phenotyping with multi-omics data (genomics, phosphoproteomics and cytomics), brain and retinal imaging, and clinical data, obtained from a multicenter prospective cohort of 328 patients and 90 healthy controls.

Predicting disease severity in multiple sclerosis using multimodal data and machine learning.

Background: Multiple sclerosis patients would benefit from machine learning algorithms that integrates clinical, imaging and multimodal biomarkers to define the risk of disease activity.

Methods: We have analysed a prospective multi-centric cohort of 322 MS patients and 98 healthy controls from four MS centres, collecting disability scales at baseline and 2 years later. Imaging data included brain MRI and optical coherence tomography, and omics included genotyping, cytomics and phosphoproteomic data from peripheral blood mononuclear cells.

CD38-Induced Metabolic Dysfunction Primes Multiple Myeloma Cells for NAD-Lowering Agents.

Cancer cells fuel growth and energy demands by increasing their NAD biosynthesis dependency, which therefore represents an exploitable vulnerability for anti-cancer strategies. CD38 is a NAD-degrading enzyme that has become crucial for anti-MM therapies since anti-CD38 monoclonal antibodies represent the backbone for treatment of newly diagnosed and relapsed multiple myeloma patients. Nevertheless, further steps are needed to enable a full exploitation of these strategies, including deeper insights of the mechanisms by which CD38 promotes tumorigenesis and its metabolic additions that could be selectively targeted by therapeutic strategies.

Impact of COVID-19 and Antibiotic Treatments on Gut Microbiome: A Role for spp.

Objective: Several studies showed the substantial use of antibiotics and increased risk of antimicrobial resistant infections in patients with COVID-19. The impact of COVID-19-related treatments and antibiotics on gut dysbiosis has not been clarified.

Design: The prospective cohort study included hospitalized COVID-19 patients (April-December 2020).

Determinants of persistence of symptoms and impact on physical and mental wellbeing in Long COVID: A prospective cohort study.

Background: Residual symptoms can be detected for several months after COVID-19. To better understand the predictors and impact of symptom persistence we analyzed a prospective cohort of COVID-19 patients.

Methods: Patients were followed for 9 months after COVID-19 onset.

Impact of Natural Killer (NK) Cells on Immune Reconstitution, and Their Potential as a Biomarker of Disease Activity, in Alemtuzumab-Treated Patients with Relapsing Remitting Multiple Sclerosis: An Observational Study.

Background: Defining immune mechanisms leading to multiple sclerosis (MS) is difficult, due to the great inter-individual difference in immune system responses. The anti-CD52 antibody alemtuzumab transiently abolishes differences in immune parameters among individuals, allowing analysis of subsequent immune cell repopulation patterns, and their possible role in MS.

Objective: To evaluate the correlation between innate and adaptive immune cell subsets and disease activity in MS in the context of treatment with alemtuzumab.

Predictors of Ocrelizumab Effectiveness in Patients with Multiple Sclerosis.

Data regarding effectiveness and safety of ocrelizumab in the post-marking setting are lacking. The aim of our study was to provide effectiveness and safety data of ocrelizumab treatment in patients with relapsing-remitting (RR-) and progressive multiple sclerosis (PMS) and to evaluate clinical and immunological predictors of early treatment response. In this single-center prospective observational study, we investigated effectiveness outcomes (time-to-confirmed disability worsening, time-to-first relapse, time-to-first evidence of MRI activity and time-to-first evidence of disease activity), clinical and immunological predictors of early treatment response, and incidence of adverse events (AEs).

Bone Marrow Transfer in Relapsing-Remitting EAE Ameliorates Disease at First Remission, with No Synergistic Effect upon Co-Transplantation with Mesenchymal Stem Cells.

Multiple sclerosis (MS) is a neurological disorder characterized by an autoimmune response, demyelinating plaques and axonal damage. Intense immunosuppression (II) followed by autologous hematopoietic stem cell transplantation has been proposed as a treatment in severe forms of MS. We have used murine relapsing-remitting (RR) experimental autoimmune encephalomyelitis (RR-EAE) to evaluate the transplantation of syngeneic bone marrow cells (BMC) after II, in combination with mesenchymal stem cells (MSCs) as a new therapeutic adjunct capable of improving immune reconstitution.

Long-Term Patient-Centred Follow-up in a Prospective Cohort of Patients with COVID-19.

Introduction: To better define COVID-19 long-term impact we prospectively analysed patient-centred outcomes, including general health and symptom duration.

Methods: Barthel index (BI), St. George's Respiratory Questionnaire adapted to patients with COVID-19 (aSGRQ) and WHO Clinical Progression Scale (CPS) were measured at enrolment and at 6 weeks from the onset of symptoms.

An Early Increase of Blood Leukocyte Subsets in Aneurysmal Subarachnoid Hemorrhage Is Predictive of Vasospasm.

Vasospasm is a severe complication in patients with aneurysmal subarachnoid hemorrhage (aSAH) and cannot be reliably predicted. Its pathophysiology remains elusive with the current body of evidence suggesting inflammation as one of the main driving forces. We here aimed to analyze circulating immune cell subsets over time in patients with aSAH with or without vasospasm.

Effect of vitamin D supplementation on N-glycan branching and cellular immunophenotypes in MS.

Objective: To investigate the effect of cholecalciferol (vitamin D3) supplementation on peripheral immune cell frequency and N-glycan branching in patients with relapsing-remitting multiple sclerosis (RRMS).

Methods: Exploratory analysis of high-dose (20 400 IU) and low-dose (400 IU) vitamin D3 supplementation taken every other day of an 18-month randomized controlled clinical trial including 38 RRMS patients on stable immunomodulatory therapy (NCT01440062). We investigated cholecalciferol treatment effects on N-glycan branching using L-PHA stain (phaseolus vulgaris leukoagglutinin) at 6 months and frequencies of T-, B-, and NK-cell subpopulations at 12 months with flow cytometry.

Sirt6 inhibition delays the onset of experimental autoimmune encephalomyelitis by reducing dendritic cell migration.

Background: Experimental autoimmune encephalomyelitis (EAE) is the most common animal model of multiple sclerosis (MS), a neuroinflammatory and demyelinating disease characterized by multifocal perivascular infiltrates of immune cells. Although EAE is predominantly considered a T helper 1-driven autoimmune disease, mounting evidence suggests that activated dendritic cells (DC), which are the bridge between innate and adaptive immunity, also contribute to its pathogenesis. Sirtuin 6 (SIRT6), a NAD-dependent deacetylase involved in genome maintenance and in metabolic homeostasis, regulates DC activation, and its pharmacological inhibition could, therefore, play a role in EAE development.

Impact of treatment on cellular immunophenotype in MS: A cross-sectional study.

Objective: To establish cytometry profiles associated with disease stages and immunotherapy in MS.

Methods: Demographic/clinical data and peripheral blood samples were collected from 227 patients with MS and 82 sex- and age-matched healthy controls (HCs) enrolled in a cross-sectional study at 4 European MS centers (Spain, Italy, Germany, and Norway). Flow cytometry of isolated peripheral blood mononuclear cells was performed in each center using specifically prepared antibody-cocktail Lyotubes; data analysis was centralized at the Genoa center.

Immunological profiles of HIV-positive recipients of liver transplant.

Background: Scarce data are available about immune cell frequencies in HIV-positive recipients of liver transplant. Alterations in immune subsets can lead to persistent immune activation and disease progression or reduced HIV-specific responses. In liver transplantation, impaired immune tolerance can lead to organ rejection.

Serological and T Cell Responses After Varicella Zoster Virus Vaccination in HIV-Positive Patients Undergoing Renal Dialysis.

Limited data on varicella zoster virus (VZV) vaccine responses are available in HIV-positive adults, especially among those with end-stage renal disease on dialysis or undergoing kidney transplantation (KT). Serological and T cell responses were analyzed using anti-VZV IgG titers, enzyme-linked immunosorbent assay and flow cytometric intracellular cytokine staining (ICS) in two HIV-positive kidney transplant candidates undergoing dialysis and receiving VZV immunization. The results were compared with two HIV-positive and two HIV-negative VZV-seropositive patients (two kidney transplant candidates and two kidney transplant recipients), and with one HIV-negative vaccinee.

CD8CD28CD127CD39 regulatory T-cell expansion: A new possible pathogenic mechanism for HIV infection?

Background: HIV-associated immunodeficiency is related to loss of CD4 T cells. This mechanism does not explain certain manifestations of HIV disease, such as immunodeficiency events in patients with greater than 500 CD4 T cells/μL. CD8CD28CD127CD39 T cells are regulatory T (Treg) lymphocytes that are highly concentrated within the tumor microenvironment and never analyzed in the circulation of HIV-infected patients.

Teriflunomide treatment reduces B cells in patients with MS.

Objective: To study the immunomodulatory effect of teriflunomide on innate and adaptive immune cell populations through a pilot, open-label, observational study in a cohort of patients with relapsing-remitting MS.

Methods: Blood lymphocytes were isolated from 10 patients with MS before and after 3 or 12 months of treatment. Adaptive and innate immune cell subsets were analyzed by flow cytometry as follows: B cells (memory, regulatory, and mature subsets), T cells (effector and regulatory subsets), and natural killer (NK) cells (CD56 and CD56 subsets).

In vitro VLA-4 blockade results in an impaired NK cell-mediated immune surveillance against melanoma.

Natalizumab (NTZ) is a monoclonal antibody targeting the α4β1 integrin (CD49d/CD29), very late antigen-4 (VLA-4), which is approved for treatment of relapsing-remitting multiple sclerosis (RR-MS). A possible association between NTZ treatment and a higher risk of melanoma is under debate. Natural Killer (NK) cells, which express VLA-4, represent an innate barrier limiting spreading of melanoma under steady state conditions.

Systemic distribution of single-walled carbon nanotubes in a novel model: alteration of biochemical parameters, metabolic functions, liver accumulation, and inflammation in vivo.

The increasing use of carbon nanotubes (CNTs) in several industrial applications raises concerns on their potential toxicity due to factors such as tissue penetrance, small dimensions, and biopersistence. Using an in vivo model for CNT environmental exposure, mimicking CNT exposition at the workplace, we previously found that CNTs rapidly enter and disseminate in the organism, initially accumulating in the lungs and brain and later reaching the liver and kidneys via the bloodstream in CD1 mice. Here, we monitored and traced the accumulation of single-walled CNTs (SWCNTs), administered systemically in mice, in different organs and the subsequent biological responses.