Publications by authors named "Giorgia Teresa Maniscalco"

The molecular mechanisms that govern differential T cell development from CD4CD25conventional T (Tconv) into CD4CD25 forkhead-box-P3 (FoxP3) inducible regulatory T (iTreg) cells remain unclear. Herein, we investigated the relative contribution of protein kinase A (PKA) in this process. Mechanistically, we found that PKA controlled the efficiency of human iTreg cell generation through the expression of different FoxP3 splicing variants containing or not the exon 2.

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  • In 2021, ofatumumab received approval for treating relapsing forms of multiple sclerosis (MS), distinguishing itself as the first subcutaneously administered anti-CD20 monoclonal antibody, unlike ocrelizumab, which is given intravenously.
  • A study analyzed Individual Case Safety Reports (ICSRs) related to injection reactions (IRRs) for both drugs from the Eudravigilance database between 2021-2023, collecting data on 860 cases, split nearly evenly between ofatumumab (51%) and ocrelizumab (49%).
  • The findings indicated that IRRs were more common with ocrelizumab, characterized by infusion-related reactions, whereas ofatumumab was primarily linked
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Objectives: We investigated the occurrence and relative contribution of relapse-associated worsening (RAW) and progression independent of relapse activity (PIRA) to confirmed disability accrual (CDA) and transition to secondary progression (SP) in relapsing multiple sclerosis (MS).

Methods: Relapsing-onset MS patients with follow-up > / = 5 years (16,130) were extracted from the Italian MS Registry. CDA was a 6-month confirmed increase in Expanded Disability Status Scale (EDSS) score.

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Background: in the early stages of Multiple Sclerosis (MS), initiating high-efficacy disease-modifying therapy (HE DMTs) may represent an optimal strategy for delaying neurological damage and long-term disease progression, especially in highly active MS patients (HAMS). Natalizumab (NAT) and Ocrelizumab (OCR) are recognized as HE DMTs with significant anti-inflammatory effects. This study investigates NEDA-3 achievement in treatment-naïve HAMS patients receiving NAT or OCR over three years.

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Treatment options for secondary progressive MS (SPMS) are limited, especially considering that the new drugs recently approved are licensed for actively relapsing patients. We aimed to compare the disability progression in a real-world cohort of SPMS patients treated with natalizumab (NTZ) or interferon beta-1b (IFNb-1b). This multicenter retrospective enrolled patients with a diagnosis of SPMS according to 2014 Lublin criteria, who received NTZ or IFNb-1b for at least 48 months between the 1st June 2012 and the 15th May 2018 ​at 33 Italian MS centers contributing to the Italian MS Registry NTZ or IFNb-1b.

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  • - The study analyzed the factors behind treatment changes in 4,739 patients with active relapsing-remitting and secondary progressive multiple sclerosis from the Italian MS Register, focusing on those who experienced relapses within the past two years.
  • - Results revealed that over half of the patients switched their disease-modifying therapy (DMT) due to clinical relapses, with those who switched being typically younger and less disabled than non-switchers.
  • - The use of high-efficacy DMTs, particularly anti-CD20 drugs like Alemtuzumab and Ocrelizumab, was shown to significantly lower the risk of needing to switch treatments due to disease activity.
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  • The study explored how pediatric-onset multiple sclerosis (POMS) compares to adult-onset (AOMS) and late-onset MS (LOMS) in terms of progression without relapse and disability levels, suggesting POMS patients may have better outcomes due to their ability to recover more effectively.* -
  • Data from over 16,000 MS patients indicated that while POMS patients showed less disability, they had higher disease activity and longer exposure to disease-modifying therapy (DMT) compared to AOMS and LOMS patients.* -
  • Key findings revealed that older age at onset and longer disease duration increased the risk of progression, while shorter DMT exposure correlated with better outcomes for POMS patients, highlighting the importance of
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(1) Background: The purpose of study was to compare the safety profile of glatiramer with natalizumab, alemtuzumab and ocrelizumab in pregnant and lactating women affected by multiple sclerosis (MS). (2) Methods: Individual case safety reports (ICSRs) were retrieved from the European spontaneous reporting system database (EudraVigilance). The reporting odds ratios (RORs) were computed to compare the reporting probability of events between natalizumab, alemtuzumab and ocrelizumab vs.

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  • COVID-19 vaccines, specifically mRNA types, have been recommended for people with multiple sclerosis (pwMS), and many have received a third booster dose for better immunity.
  • A study involving 1265 pwMS investigated the short-term risk of disease reactivation after this booster shot, assessing relapse rates before and after vaccination.
  • The results showed no significant increase in relapse rates post-booster (2.1%) compared to the rates before vaccination (1.9%), indicating that the third booster dose is likely safe for pwMS.
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Background: Cladribine belongs to the group of disease-modifying therapies (DMTs) used to treat multiple sclerosis (MS). According to the highlights of a meeting held by the Pharmacovigilance Risk Assessment Committee (PRAC) on 14 January 2022, cladribine may be associated with the occurrence of liver injury, and thus liver function monitoring is recommended.

Objectives And Methods: Using data from the European spontaneous reporting database (EudraVigilance-EV), we aimed to describe the main characteristics of Individual Case Safety Reports (ICSRs) reporting cases of hepatobiliary disorders related to cladribine.

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Since the beginning of the mass immunization of patients with multiple sclerosis (MS), many data on the efficacy and safety of COVID-19 vaccines have been produced. Considering that MS is an autoimmune disease and that some disease-modifying therapies (DMTs) could decrease the antibody response against COVID-19 vaccines, we carried out this retrospective study with the aim to evaluate the safety of these vaccines in terms of AEFI occurrence and the antibody response after MS patients had received the third dose. Two hundred and ten patients (64.

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  • The study investigates the relationship between myelin oligodendrocyte glycoprotein antibody associated disease (MOGAD) and tumors, finding only 1% of MOGAD patients had a neoplasm within 2 years of disease onset.
  • It reports on a total of 17 cases (including two from their cohort and 15 from literature), highlighting that most patients are around 39 years old with varied clinical presentations (like ADEM and optic neuritis).
  • The findings suggest MOG antibodies have a low association with paraneoplastic neurological syndromes, with a wide range of tumor types observed and a high rate of treatment improvement in patients.
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Background And Purpose: Longitudinally extensive transverse myelitis (LETM) associated with aquaporin-4 autoantibodies (AQP4-IgG) can cause severe disability. Early diagnosis and prompt treatment are critical to prevent relapses. A novel score is described based on clinical and neuroimaging characteristics that predicts AQP4-IgG positivity in patients with LETM.

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Introduction: The diagnosis of the progression phase of Multiple Sclerosis (MS) is still retrospective and based on the objectivation of clinical disability accumulation.

Objectives: To assess whether the Patient Reported Outcomes Measures (PROMs) scores predict the occurrence of disease progression within three years of follow-up.

Methods: Observational prospective multicenter study.

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Background: It remains unclear how vaccine doses and combinations of vaccination and infection affect the magnitude and quality of immune responses, particularly against novel SARS-CoV-2 variants in subjects with immune-related disorders, such as people with multiple sclerosis (pwMS). Several studies have evaluated the duration of anti-SARS-CoV-2 immune protection in healthy individuals; however clinical data suggest an attenuated short-term humoral response to SARS-CoV-2 vaccines in pwMS receiving disease-modifying therapies (DMTs).

Methods: In this prospective study, we evaluated the humoral response to the third (3rd) BNT162b2 vaccine (booster) dose in a monocentric cohort of pwMS undergoing eight different DMTs, all without previous SARS-CoV-2 infection.

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In the current COVID-19 pandemic, patients diagnosed with multiple sclerosis (MS) are considered to be one of the highest priority categories, being recognized as extremely vulnerable people. For this reason, mRNA-based COVID-19 vaccines are strongly recommended for these patients. Despite encouraging results on the efficacy and safety profile of mRNA-based COVID-19 vaccines, to date, in frail populations, including patients diagnosed with MS, this information is rather limited.

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Objective: Multiple sclerosis (MS) is a chronic disease with different clinical courses and a tendency to worsening. The relapsing-remitting MS presents acute onset and relapses of neurological symptoms, followed by their remission. This form can convert to secondary progressive MS (SPMS) with irreversible neurological worsening and disability.

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Epigenetics connects genetic and environmental factors: it includes DNA methylation, histone post-translational modifications and the regulation of chromatin accessibility by non-coding RNAs, all of which control constitutive or inducible gene transcription. This plays a key role in harnessing the transcriptional programs of both innate and adaptive immune cells due to its plasticity and environmental-driven nature, piloting myeloid and lymphoid cell fate decisions with no change in their genomic sequence. In particular, epigenetic marks at the site of lineage-specific transcription factors and maintenance of cell type-specific epigenetic modifications, referred to as 'epigenetic memory', dictate cell differentiation, cytokine production and functional capacity following repeated antigenic exposure in memory T cells.

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Background: Definitions for reliable identification of transition from relapsing-remitting multiple sclerosis (MS) to secondary progressive (SP)MS in clinical cohorts are not available.

Objectives: To compare diagnostic performances of two different data-driven SPMS definitions.

Methods: Data-driven SPMS definitions based on a version of Lorscheider's algorithm (DDA) and on the EXPAND trial inclusion criteria were compared, using the neurologist's definition (ND) as gold standard, in terms of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), Akaike information criterion (AIC) and area under the curve (AUC).

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Introduction: Cladribine administration has been approved for the treatment of relapsing-remitting multiple sclerosis (MS) in 2017; thus, data on cladribine in a real-world setting are still emerging.

Methods: We report on cladribine effectiveness, safety profile, and treatment response predictors in 243 patients with MS followed at eight tertiary MS centers. Study outcomes were: (1) No Evidence of Disease Activity-3 (NEDA-3) status and its components (absence of clinical relapses, MRI activity, and sustained disability worsening); (2) development of grade III/IV lymphopenia.

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Objectives: In this retrospective multicenter study, we evaluated the safety of SARS-CoV-2 vaccination in patients harboring autoantibodies targeting neuronal surface and/or synaptic antigens.

Methods: From eight Italian Neurology Units, we included patients with: a) serum and/or CSF positivity for specific neuronal autoantibodies; b) a compatible neurological syndrome; and c) available follow-up ≥6 weeks after vaccination with any of the approved SARS-CoV-2 vaccines. Demographics, clinical data, and information regarding previous SARS-CoV-2 infection and vaccination were collected.

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Background & Objectives: The persistence of the severe acute respiratory syndrome coronavirus (SARS-CoV)-2 pandemic, partly due to the appearance of highly infectious variants, has made booster vaccinations necessary for vulnerable groups. Here, we present data regarding the decline of the SARS-CoV-2 BNT162b2 mRNA vaccine-induced humoral immune response in a monocentric cohort of MS patients.

Methods: 96 MS patients undergoing eight different DMTs, all without previous SARS-CoV-2 infection, were evaluated for anti-Spike IgG levels, 21 days (T1) and 5-6 months (T2) after the second SARS-CoV-2 BNT162b2 mRNA vaccine dose.

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