Dataset Information

Increased B cell and cytotoxic NK cell proportions and increased T cell responsiveness in blood of natalizumab-treated multiple sclerosis patients.

ABSTRACT:

Background

Changes in the blood lymphocyte composition probably both mediate and reflect the effects of natalizumab treatment in multiple sclerosis, with implications for treatment benefits and risks.

Methods

A broad panel of markers for lymphocyte populations, including states of activation and co-stimulation, as well as functional T cell responses to recall antigens and mitogens, were assessed by flow cytometry in 40 patients with relapsing multiple sclerosis before and after one-year natalizumab treatment.

Results

Absolute numbers of all major lymphocyte populations increased after treatment, most markedly for NK and B cells. The fraction of both memory and presumed regulatory B cell subsets increased, as did CD3(-)CD56(dim) cytotoxic NK cells, whereas CD3(-)CD56(bright) regulatory NK cells decreased. The increase in cell numbers was further associated with a restored T cell responsiveness to recall antigens and mitogens in functional assays.

Conclusions

Our data confirms that natalizumab treatment increases the number of lymphocytes in blood, likely mirroring the expression of VLA-4 being highest on NK and B cells. This finding supports reduction of lymphocyte extravasation as a main mode of action, although the differential effects on subpopulation composition suggests that cell-signalling may also be affected. The systemic increase in T cell responsiveness reflects the increase in numbers, and while augmenting anti-infectious responses systemically, localized responses may become correspondingly decreased.

SUBMITTER: Mellergard J

PROVIDER: S-EPMC3847051 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

Increased B cell and cytotoxic NK cell proportions and increased T cell responsiveness in blood of natalizumab-treated multiple sclerosis patients.

Mellergård Johan J Edström Måns M Jenmalm Maria C MC Dahle Charlotte C Vrethem Magnus M Ernerudh Jan J

PloS one 20131202 12

<h4>Background</h4>Changes in the blood lymphocyte composition probably both mediate and reflect the effects of natalizumab treatment in multiple sclerosis, with implications for treatment benefits and risks.<h4>Methods</h4>A broad panel of markers for lymphocyte populations, including states of activation and co-stimulation, as well as functional T cell responses to recall antigens and mitogens, were assessed by flow cytometry in 40 patients with relapsing multiple sclerosis before and after on ...[more]

PMID: 24312575

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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

Increased B cell and cytotoxic NK cell proportions and increased T cell responsiveness in blood of natalizumab-treated multiple sclerosis patients.

Background

Methods

Results

Conclusions

Publications

Increased B cell and cytotoxic NK cell proportions and increased T cell responsiveness in blood of natalizumab-treated multiple sclerosis patients.

Similar Datasets

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