Publications by authors named "Laura Gragnani"

Background: The health of the marginalized populations is crucial for public health and inequalities. The World Health Organization (WHO) Global Hepatitis Report 2024 stated that over 304 million people were living with Hepatitis B Virus (HBV)/Hepatitis C Virus (HCV) infection in 2022. We performed HBV/HCV screenings among marginalized communities to reveal hidden infections and link-to-care positive participants.

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Background: Novel circulating markers for the non-invasive staging of chronic liver disease (CLD) are in high demand. Although underutilized, extracellular matrix (ECM) components offer significant diagnostic potential. This study evaluates ECM-related markers in hepatitis C virus (HCV)-positive patients across varying fibrosis stages.

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Systemic lupus erythematosus (SLE) is characterized by B cell dysregulation and expansion of atypical B cells that may correlate with disease manifestations and activity. This study investigated the impact of subcutaneous (sc) Belimumab (BLM) on the peripheral B cell compartment and on the functional properties of CD21, T-bet and CD11c atypical B cells, in 21 active SLE patients over a 12-month period. At baseline, active SLE patients displayed reduced unswitched IgM memory B cells and expansion of atypical B cells, compared to healthy donors and to SLE patients in remission.

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Introduction: The impact of COVID-19 pandemic represents a serious challenge for 'frail' patients' populations with inflammatory autoimmune systemic diseases such as systemic sclerosis (SSc). We investigated the prevalence and severity of COVID-19, as well the effects of COVID-19 vaccination campaign in a large series of SSc patients followed for the entire period (first 38 months) of pandemic.

Patients And Method: This prospective survey study included 1755 unselected SSc patients (186 M, 1,569F; mean age 58.

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Article Synopsis
  • SARS-CoV-2, the virus responsible for COVID-19, can enter cells through the ACE2 receptor, which is found in various tissues, including the thyroid.
  • The virus has been linked to several thyroid disorders, such as subacute thyroiditis and autoimmune thyroid diseases, potentially due to its replication in the gland.
  • Proposed mechanisms for how SARS-CoV-2 may trigger autoimmune responses include immune system overactivity and molecular mimicry, but further research is needed to solidify these connections.
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Studies from high endemic areas, mostly China, indicate that surface antigen positive (HBsAg) chronic hepatitis B virus (HBV) infection is associated with an increased risk of developing diffuse large B-cell lymphoma (DLBCL), whereas studies in low endemic areas have provided conflicting results. Past infection, serologically defined by negative HBsAg and positive anti-core antibody (HBsAgHBcAb), has also been suggested to increase the risk of B-cell non-Hodgkin's lymphoma (NHL) in high endemic areas. We retrospectively reviewed unselected clinical records of 253 patients with DLBCL (54% male, aged 60.

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Article Synopsis
  • The study evaluated the expression of specific miRNAs (miR-223-3p, miR-17-5p, and miR-24-3p) in the serum of hepatitis C virus (HCV) patients before and after treatment.
  • Results showed that after achieving sustained virological response (SVR), these miRNAs were significantly downregulated in patients with cirrhosis and hepatocellular carcinoma, indicating a potential link between miRNA levels and liver damage stages.
  • This research is notable as it is the first to explore the changes in miRNA profiles in HCV patients in relation to the effectiveness of direct-acting antiviral (DAA) therapies, suggesting that these miRNAs might play a role
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Prolonged B cells stimulation due to the Hepatitis C virus (HCV) can result in autoimmunity, stigmatized by rising levels of cryoglobulins (CGs), the rheumatoid factor (RF), and free light chains (FLC) of immunoglobulins (Ig) associated with a range of symptoms, from their absence to severe cryoglobulinemic vasculitis and lymphoma. Here, we aimed to identify an immunological signature for the earliest stages of vasculitis when cryoprecipitate is still not detectable. We firstly analyzed the IgG subclasses, FLC, and RF in 120 HCV-RNA-positive patients divided into four groups according to the type of cryoprecipitate and symptoms: 30 asymptomatic without cryoprecipitate (No Cryo), 30 with vasculitis symptoms but without CGs that we supposed were circulating but still not detectable (Circulating), 30 type II and 30 type III mixed cryoglobulinemia (Cryo II and Cryo III, respectively).

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We investigated 23 hepatitis C virus (HCV)-infected patients with overt lymphoproliferative diseases (15 cases) or monoclonal B lymphocytosis (8 cases) treated with direct agent antiviral (DAAs) per clinical practice. DAA therapy yielded undetectable HCV-RNA, the complete response of cryoglobulinemia vasculitis and related signs, whilst the presence of B-cell clones (evaluated by flow cytometry, IGHV, and BCL2-IGH rearrangements), detected in 19/23 cases at baseline, was maintained (17/19). Similarly, IGHV intraclonal diversification, supporting an antigen-driven selection mechanism, was identified in B-cell clones at baseline and end of follow-up.

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Introduction: Hepatitis C virus (HCV) causes mixed cryoglobulinemia (MC) by driving clonal expansion of B cells expressing B cell receptors (BCRs), often encoded by the VH1-69 variable gene, endowed with both rheumatoid factor (RF) and anti-HCV specificity. These cells display an atypical CD21low phenotype and functional exhaustion evidenced by unresponsiveness to BCR and Toll-like receptor 9 (TLR9) stimuli. Although antiviral therapy is effective on MC vasculitis, pathogenic B cell clones persist long thereafter and can cause virus-independent disease relapses.

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New-generation mRNA and adenovirus vectored vaccines against SARS-CoV-2 spike protein are endowed with immunogenic, inflammatory and immunomodulatory properties. Recently, BioNTech developed a noninflammatory tolerogenic mRNA vaccine (MOGm1Ψ) that induces in mice robust expansion of antigen-specific regulatory T (Treg) cells. The Pfizer/BioNTech BNT162b2 mRNA vaccine against SARS-CoV-2 is identical to MOGm1Ψ except for the lipid carrier, which differs for containing lipid nanoparticles rather than lipoplex.

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Objective: Hepatitis B virus (HBV) infection causes chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Furthermore, about 20% of the patients develop extrahepatic manifestations such as cryoglobulinemic vasculitis (CV), polyarteritis nodosa, non-rheumatoid arthritis, glomerulonephritis and non-Hodgkin lymphoma. This review analyzed literature data on clinical manifestations of HBV-related CV and the impact of antiviral therapy with analoques nucleotide.

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Hepatitis C virus (HCV) is a hepatotropic and lymphotropic virus, responsible for both chronic hepatitis and extra-hepatic manifestations. Multiple epidemiologic, clinical, biological, and molecular studies have suggested that HCV plays a causal role also in the development of several lymphoproliferative disorders, either benign, such as mixed cryoglobulinemia, or malignant, such as B-cell non-Hodgkin lymphomas (NHL). Chronic viral antigenic stimulation of B-lymphocytes plays a fundamental basic role from the onset of lymphoma to its final steps.

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Purpose: Mixed cryoglobulinemia syndrome (MCs) is a rare immunoproliferative systemic disorder with cutaneous and multiple organ involvement. Our multicenter survey study aimed to investigate the prevalence and outcome of COVID-19 and the safety and immunogenicity of COVID-19 vaccines in a large MCs series.

Methods: The survey included 430 unselected MCs patients (130 M, 300 F; mean age 70 ± 10.

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Background: Patients with autoimmune systemic diseases (ASDs) represent a frail population during the ongoing COVID-19 pandemic. The vaccination is the major preventive measure; however, a significant number of ASD patients show an impaired production of anti-COVID-19 neutralizing antibodies (NAb), possibly counterbalanced by adequate T-cell response. The present study aimed at evaluating both humoral and cellular response to COVID-19 vaccine booster dose in this particular setting.

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Since the beginning of the pandemic, numerous risk factors have been associated with SARS-CoV-2 infection and COVID-19 outcomes, such as older age, male sex, and the presence of comorbidities, such as hypertension, obesity, and diabetes. Preliminary data also suggest epidemiological association between SARS-CoV-2 infection and systemic autoimmune disease. For this reason, we investigated if patients affected by autoimmune thyroid disorders (AITD) are at risk of developing SARS-CoV-2 infection or COVID-19 disease.

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Objectives: Mixed cryoglobulinaemic vasculitis (MCV) is an immune-complex-mediated systemic vasculitis characterised by heterogeneous clinical manifestations mainly involving lymphatic system, skin, kidney and peripheral nervous system. Although MCV patients have been included in priority programs for vaccination against SARS-CoV-2 in Italy, limited information is available for these patients. The aims of this multicentre Italian study were to investigate SARS-CoV-2 vaccination rate in MCV patients and its safety profile.

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Article Synopsis
  • Autoimmune systemic diseases (ASD) patients exhibit reduced immunogenic response to COVID-19 vaccines compared to age-matched controls, even after receiving booster doses.
  • In a study involving 478 ASD patients, antibody levels after vaccination significantly increased post-booster, but still remained lower than those of control participants.
  • After booster vaccination, the proportion of ASD patients showing absent or suboptimal vaccine response dropped notably, yet a significant percentage (7.8%) still lacked effective seroconversion, highlighting the need for ongoing monitoring.
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Article Synopsis
  • Autoimmune systemic diseases (ASD) increase the likelihood of contracting COVID-19, with a study of nearly 4,000 Italian ASD patients revealing a higher infection rate compared to the general population.
  • While ASD patients had more cases of COVID-19, their death rate was similar to that of the overall Italian population, though systemic sclerosis patients faced a higher risk of mortality.
  • Key factors influencing the severity of COVID-19 in ASD patients included older age, male gender, and certain medical treatments, with those on specific medications showing a significantly lower infection prevalence.
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Cryoglobulinemic Vasculitis (CV) is an autoimmune/lymphoproliferative disorder associated with HCV infection that in 5%-10% of cases evolves into a B cell Non-Hodgkin's Lymphoma (NHL). B-cell activating factor (BAFF) is a key regulator in B-cell development and survival. Particular genetic variants are responsible for BAFF signaling impairment in autoimmune and neoplastic diseases.

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Background And Aims: Mixed cryoglobulinemia is the most common HCV extrahepatic manifestation. We aimed to prospectively evaluate the cryoglobulinemic vasculitis (CV) clinical profile after a sustained virologic response (SVR) over a medium-term to long-term period.

Approach And Results: Direct-acting antiviral-treated cryoglobulinemic patients, consecutively enrolled in the multicentric Italian Platform for the Study of Viral Hepatitis Therapy cohort, were prospectively evaluated.

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Autoimmune systemic diseases (ASD) may show impaired immunogenicity to COVID-19 vaccines. Our prospective observational multicenter study aimed to evaluate the seroconversion after the vaccination cycle and at 6-12-month follow-up, as well the safety and efficacy of vaccines in preventing COVID-19. The study included 478 unselected ASD patients (mean age 59 ± 15 years), namely 101 rheumatoid arthritis (RA), 38 systemic lupus erythematosus (SLE), 265 systemic sclerosis (SSc), 61 cryoglobulinemic vasculitis (CV), and a miscellanea of 13 systemic vasculitis.

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Background: The Covid-19 pandemic may have a deleterious impact on patients with autoimmune systemic diseases (ASD) due to their deep immune-system alterations.

Objective: This study aims to investigate the prevalence of symptomatic Covid-19 and its correlations with both organ involvement and ongoing treatments in a large series of Italian ASD patients during the first wave of pandemic.

Methods: Our multicenter telephone 6-week survey included 3,029 unselected ASD patients enrolled at 36 tertiary referral centers of northern, central, and southern Italian macro-areas with different diffusion of the pandemic.

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