Effect of Alemtuzumab (LEMTRADA®) treatment on the peripheral immune repertoire in multiple sclerosis patients
ECTRIMS Online Library. Barman S. 09/13/19; 278699; P1660
Sumanta Barman
Sumanta Barman
Contributions
Abstract

Abstract: P1660

Type: Poster Sessions

Abstract Category: Poster Session 3

S. Barman1, A. Scheffler1, T. Ruck2, C. Lehrich2, A. Coordt1, P. Sporkmann1, H. Wiendl2, S. Meuth2, H.-P. Hartung1, N. Melzer2, N. Goebels1

1Department of Neurology, University Hospital Düsseldorf, Düsseldorf, 2Department of Neurology, University Hospital Münster, Münster, Germany

Introduction: Alemtuzumab (LEMTRADA®) is a recombinant, humanized, anti-CD52 IgG1 monoclonal antibody that selectively depletes T and B lymphocytes.
Aims: This study aims to characterize longitudinal changes in the clonal compositions of multiple sclerosis (MS) patients' peripheral lymphocyte repertoires before and during Alemtuzumab treatment, to better understand the beneficial properties and potential side effects of this drug.
Methods: The T cell receptor (TCR) repertoire of CD4+ and CD8+ T cells, and expressed immunoglobulin genes (Ig) of naïve and memory B cells, FACS-purified from peripheral blood of 10 patients with MS before and three timepoints within 24 months after onset of treatment with Alemtuzumab, and controls were analyzed by next generation sequencing (Illumina Miseq).
Results: Longitudinal FACS analysis data confirmed a strong decrease of particularly CD4+, but also CD8+ T lymphocytes after each antibody infusion, while a moderate reduction of the memory B cell population was observed. In contrast, an increase of the naïve B cell population was noticeable. Clonotype tracking data revealed that strongly expanded T cell clones dominate the CD8+ T cell compartment, which majorly persist, with some fluctuations, during treatment. In contrast, the CD4+ compartment consists of many, quite homogeneously distributed T cell clones of low abundance. Alemtuzumab treatment induces clonal expansions of some CD4+ T cell clones. In contrast, the IgG+ memory B cell compartment contains strongly expanded clones, which - in untreated individuals - hardly persist over time. Here, Alemtuzumab treatment seems to promote persistence of some memory IgG+ B cell clones. In all three lymphocyte populations, Alemtuzumab treatment seems to 'reshuffle' the 'Top 100' clones, including some apparent clonal 'losses', with partial recovery over time, and expansion of new clones.
Conclusions: Results analyzed so far show remarkably characteristic patterns of clonal expansion, clonal abundance and clonal evolution/persistence over time of individual lymphocyte subpopulations, which are differentially affected by Alemtuzumab treatment. Further data analysis and correlation with clinical data is ongoing to better understand which of the observed effects are responsible for maintaining immune competence, a beneficial 'remolding'' of autoaggressive immune components or the development of secondary autoimmune conditions under Alemtuzumab treatment.
Disclosure: SB, AS, TR, CL, AC, PS, HW, SM, NM have nothing to disclose.
NG, HPH: This study was supported by Sanofi-Genzyme.

Abstract: P1660

Type: Poster Sessions

Abstract Category: Poster Session 3

S. Barman1, A. Scheffler1, T. Ruck2, C. Lehrich2, A. Coordt1, P. Sporkmann1, H. Wiendl2, S. Meuth2, H.-P. Hartung1, N. Melzer2, N. Goebels1

1Department of Neurology, University Hospital Düsseldorf, Düsseldorf, 2Department of Neurology, University Hospital Münster, Münster, Germany

Introduction: Alemtuzumab (LEMTRADA®) is a recombinant, humanized, anti-CD52 IgG1 monoclonal antibody that selectively depletes T and B lymphocytes.
Aims: This study aims to characterize longitudinal changes in the clonal compositions of multiple sclerosis (MS) patients' peripheral lymphocyte repertoires before and during Alemtuzumab treatment, to better understand the beneficial properties and potential side effects of this drug.
Methods: The T cell receptor (TCR) repertoire of CD4+ and CD8+ T cells, and expressed immunoglobulin genes (Ig) of naïve and memory B cells, FACS-purified from peripheral blood of 10 patients with MS before and three timepoints within 24 months after onset of treatment with Alemtuzumab, and controls were analyzed by next generation sequencing (Illumina Miseq).
Results: Longitudinal FACS analysis data confirmed a strong decrease of particularly CD4+, but also CD8+ T lymphocytes after each antibody infusion, while a moderate reduction of the memory B cell population was observed. In contrast, an increase of the naïve B cell population was noticeable. Clonotype tracking data revealed that strongly expanded T cell clones dominate the CD8+ T cell compartment, which majorly persist, with some fluctuations, during treatment. In contrast, the CD4+ compartment consists of many, quite homogeneously distributed T cell clones of low abundance. Alemtuzumab treatment induces clonal expansions of some CD4+ T cell clones. In contrast, the IgG+ memory B cell compartment contains strongly expanded clones, which - in untreated individuals - hardly persist over time. Here, Alemtuzumab treatment seems to promote persistence of some memory IgG+ B cell clones. In all three lymphocyte populations, Alemtuzumab treatment seems to 'reshuffle' the 'Top 100' clones, including some apparent clonal 'losses', with partial recovery over time, and expansion of new clones.
Conclusions: Results analyzed so far show remarkably characteristic patterns of clonal expansion, clonal abundance and clonal evolution/persistence over time of individual lymphocyte subpopulations, which are differentially affected by Alemtuzumab treatment. Further data analysis and correlation with clinical data is ongoing to better understand which of the observed effects are responsible for maintaining immune competence, a beneficial 'remolding'' of autoaggressive immune components or the development of secondary autoimmune conditions under Alemtuzumab treatment.
Disclosure: SB, AS, TR, CL, AC, PS, HW, SM, NM have nothing to disclose.
NG, HPH: This study was supported by Sanofi-Genzyme.

By clicking “Accept Terms & all Cookies” or by continuing to browse, you agree to the storing of third-party cookies on your device to enhance your user experience and agree to the user terms and conditions of this learning management system (LMS).

Cookie Settings
Accept Terms & all Cookies