Dataset Information

T Lymphocyte Serotonin 5-HT₇ Receptor Is Dysregulated in Natalizumab-Treated Multiple Sclerosis Patients.

ABSTRACT: Serotonin (5-HT) is known as a potent immune cell modulator in autoimmune diseases and should be protective in the pathogenesis of multiple sclerosis (MS). Nevertheless, there is limited knowledge about receptors involved in 5-HT effects as well as induced mechanisms. Among 5-HT receptors, the 5-HT₇ receptor is able to activate naïve T cells and influence the inflammatory response; however, its involvement in the disease has never been studied so far. In this study, we collected blood sample from three groups: acute relapsing MS patients (ARMS), natalizumab-treated MS patients (NTZ), and control subjects. We investigated the 5-HT₇ expression on circulating lymphocytes and evaluated the effects of its activation on cytokine production with peripheral blood mononuclear cell (PBMC) cultures. We found a significant increase in the 5-HT₇ surface expression on T lymphocytes and on the different CD4⁺ T cell subsets exclusively in NTZ-treated patients. We also showed that the selective agonist 5-carboxamidotryptamine (5-CT)-induced 5-HT₇R activation significantly promotes the production of IL-10, a potent immunosuppressive cytokine in PBMCs. This study provides for the first time a dysregulation of 5-HT₇ expression in NTZ-MS patients and its ability to promote IL-10 release, suggesting its protective role. These findings strengthen the evidence that 5-HT₇ may play a role in the immuno-protective mechanisms of NTZ in MS disease and could be considered as an interesting therapeutic target in MS.

SUBMITTER: Reverchon F

PROVIDER: S-EPMC9599221 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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T Lymphocyte Serotonin 5-HT<sub>7</sub> Receptor Is Dysregulated in Natalizumab-Treated Multiple Sclerosis Patients.

Reverchon Flora F Guillard Colleen C Mollet Lucile L Auzou Pascal P Gosset David D Madouri Fahima F Valéry Antoine A Menuet Arnaud A Ozsancak Canan C Pallix-Guyot Maud M Morisset-Lopez Séverine S

Biomedicines 20220927 10

Serotonin (5-HT) is known as a potent immune cell modulator in autoimmune diseases and should be protective in the pathogenesis of multiple sclerosis (MS). Nevertheless, there is limited knowledge about receptors involved in 5-HT effects as well as induced mechanisms. Among 5-HT receptors, the 5-HT<sub>7</sub> receptor is able to activate naïve T cells and influence the inflammatory response; however, its involvement in the disease has never been studied so far. In this study, we collected blood ...[more]

PMID: 36289679

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Project description:ImportanceVaccination in patients with highly active multiple sclerosis (MS) requiring prompt treatment initiation may result in impaired vaccine responses and/or treatment delay.ObjectiveTo assess the immunogenicity and safety of inactivated vaccines administered during natalizumab treatment.Design, setting, and participantsThis self-controlled, prospective cohort study followed adult patients with MS from 1 study center in Spain from September 2016 to February 2022. Eligible participants included adults with MS who completed immunization for hepatitis B virus (HBV), hepatitis A virus (HAV), and COVID-19 during natalizumab therapy. Data analysis was conducted from November 2022 to February 2023.ExposuresPatients were categorized according to their time receiving natalizumab treatment at the time of vaccine administration as short-term (≤1 year) or long-term (>1 year).Main outcomes and measuresDemographic, clinical, and radiological characteristics were collected during the year before vaccination (prevaccination period) and the year after vaccination (postvaccination period). Seroprotection rates and postvaccination immunoglobulin G titers were determined for each vaccine within both periods. Additionally, differences in annualized relapse rate (ARR), new T2 lesions (NT2L), Expanded Disability Status Scale (EDSS) scores, and John Cunningham virus (JCV) serostatus between the 2 periods were assessed.ResultsSixty patients with MS (mean [SD] age, 43.2 [9.4] years; 44 female [73.3%]; 16 male [26.7%]; mean [SD] disease duration, 17.0 [8.7] years) completed HBV, HAV, and mRNA COVID-19 immunization during natalizumab treatment, with 12 patients in the short-term group and 48 patients in the long-term group. The global seroprotection rate was 93% (95% CI, 86%-98%), with individual vaccine rates of 92% for HAV (95% CI, 73%-99%), 93% for HBV (95% CI, 76%-99%), and 100% for the COVID-19 messenger RNA vaccine (95% CI, 84%-100%). Between the prevaccination and postvaccination periods there was a significant reduction in the mean (SD) ARR (0.28 [0.66] vs 0.01 [0.12]; P = .004) and median (IQR) NT2L (5.00 [2.00-10.00] vs 0.81 [0.00-0.50]; P = .01). No changes in disability accumulation were detected (median [IQR] EDSS score 3.5 [2.0-6.0] vs 3.5 [2.0-6.0]; P = .62). No differences in safety and immunogenicity were observed for all vaccines concerning the duration of natalizumab treatment.Conclusions and relevanceThe findings of this cohort study suggest that immunization with inactivated vaccines during natalizumab therapy was both safe and immunogenic, regardless of the treatment duration. Natalizumab may be a valuable option for proper immunization, averting treatment delays in patients with highly active MS; however, this strategy needs to be formally evaluated.

Dataset Information

T Lymphocyte Serotonin 5-HT₇ Receptor Is Dysregulated in Natalizumab-Treated Multiple Sclerosis Patients.

Publications

T Lymphocyte Serotonin 5-HT<sub>7</sub> Receptor Is Dysregulated in Natalizumab-Treated Multiple Sclerosis Patients.

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Dataset Information

T Lymphocyte Serotonin 5-HT7 Receptor Is Dysregulated in Natalizumab-Treated Multiple Sclerosis Patients.

Publications

T Lymphocyte Serotonin 5-HT<sub>7</sub> Receptor Is Dysregulated in Natalizumab-Treated Multiple Sclerosis Patients.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

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T Lymphocyte Serotonin 5-HT₇ Receptor Is Dysregulated in Natalizumab-Treated Multiple Sclerosis Patients.