The effect of glatiramer acetate therapy on functional properties of B cells from patients with relapsing-remitting multiple sclerosis

Sara J. Ireland, Alyssa A. Guzman, Dina E. O'Brien, Samuel Hughes, Benjamin Greenberg, Angela Flores, Donna Graves, Gina Remington, Elliot Frohman, Laurie S Davis, Nancy L Monson

Research output: Contribution to journalArticle

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Abstract

IMPORTANCE: This study describes what is, to our knowledge, the previously unknown effect of glatiramer acetate therapy on B cells in patients with relapsing-remitting multiple sclerosis (MS). OBJECTIVE: To determine whether glatiramer acetate therapy normalizes dysregulated B-cell proliferation and cytokine production in patients with MS. DESIGN, SETTING, AND PARTICIPANTS: Twenty-two patients with MS whowere receiving glatiramer acetate therapy and 22 treatment-naive patients with MS were recruited at The University of Texas Southwestern Medical Center MS clinic. Cell samples from healthy donors were obtained from HemaCare (Van Nuys, California) or Carter Blood Bank (Dallas, Texas). Treatment-naive patients with MS had not received any disease-modifying therapies for at least 3 months before the study. EXPOSURES: Glatiramer acetate therapy for at least 3 months at the time of the study. MAIN OUTCOMES AND MEASURES: B-cell phenotype and proliferation and immunoglobulin and cytokine secretion. RESULTS: A restoration of interleukin 10 production by peripheral B cells was observed in patients undergoing glatiramer acetate therapy as well as a significant reduction of interleukin 6 production in a subset of patients who received therapy for less than 32 months. Furthermore, proliferation in response to high-dose CD40L was altered and immunoglobulin production was elevated in in vitro-activated B cells obtained from patients who received glatiramer acetate. CONCLUSIONS AND RELEVANCE: Glatiramer acetate therapy remodels the composition of the B-cell compartment and influences cytokine secretion and immunoglobulin production. These data suggest that glatiramer acetate therapy affects several aspects of dysregulated B-cell function in MS that may contribute to the therapeutic mechanisms of glatiramer acetate.

Original languageEnglish (US)
Pages (from-to)1421-1428
Number of pages8
JournalJAMA Neurology
Volume71
Issue number11
DOIs
StatePublished - Nov 1 2014

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Relapsing-Remitting Multiple Sclerosis
B-Lymphocytes
Multiple Sclerosis
Therapeutics
Immunoglobulins
Cytokines
Glatiramer Acetate
Cells
Therapy
Cell Proliferation
Blood Banks
CD40 Ligand
Time and Motion Studies
Interleukin-10
Interleukin-6

ASJC Scopus subject areas

  • Arts and Humanities (miscellaneous)
  • Clinical Neurology

Cite this

The effect of glatiramer acetate therapy on functional properties of B cells from patients with relapsing-remitting multiple sclerosis. / Ireland, Sara J.; Guzman, Alyssa A.; O'Brien, Dina E.; Hughes, Samuel; Greenberg, Benjamin; Flores, Angela; Graves, Donna; Remington, Gina; Frohman, Elliot; Davis, Laurie S; Monson, Nancy L.

In: JAMA Neurology, Vol. 71, No. 11, 01.11.2014, p. 1421-1428.

Research output: Contribution to journalArticle

Ireland, Sara J. ; Guzman, Alyssa A. ; O'Brien, Dina E. ; Hughes, Samuel ; Greenberg, Benjamin ; Flores, Angela ; Graves, Donna ; Remington, Gina ; Frohman, Elliot ; Davis, Laurie S ; Monson, Nancy L. / The effect of glatiramer acetate therapy on functional properties of B cells from patients with relapsing-remitting multiple sclerosis. In: JAMA Neurology. 2014 ; Vol. 71, No. 11. pp. 1421-1428.
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abstract = "IMPORTANCE: This study describes what is, to our knowledge, the previously unknown effect of glatiramer acetate therapy on B cells in patients with relapsing-remitting multiple sclerosis (MS). OBJECTIVE: To determine whether glatiramer acetate therapy normalizes dysregulated B-cell proliferation and cytokine production in patients with MS. DESIGN, SETTING, AND PARTICIPANTS: Twenty-two patients with MS whowere receiving glatiramer acetate therapy and 22 treatment-naive patients with MS were recruited at The University of Texas Southwestern Medical Center MS clinic. Cell samples from healthy donors were obtained from HemaCare (Van Nuys, California) or Carter Blood Bank (Dallas, Texas). Treatment-naive patients with MS had not received any disease-modifying therapies for at least 3 months before the study. EXPOSURES: Glatiramer acetate therapy for at least 3 months at the time of the study. MAIN OUTCOMES AND MEASURES: B-cell phenotype and proliferation and immunoglobulin and cytokine secretion. RESULTS: A restoration of interleukin 10 production by peripheral B cells was observed in patients undergoing glatiramer acetate therapy as well as a significant reduction of interleukin 6 production in a subset of patients who received therapy for less than 32 months. Furthermore, proliferation in response to high-dose CD40L was altered and immunoglobulin production was elevated in in vitro-activated B cells obtained from patients who received glatiramer acetate. CONCLUSIONS AND RELEVANCE: Glatiramer acetate therapy remodels the composition of the B-cell compartment and influences cytokine secretion and immunoglobulin production. These data suggest that glatiramer acetate therapy affects several aspects of dysregulated B-cell function in MS that may contribute to the therapeutic mechanisms of glatiramer acetate.",
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T1 - The effect of glatiramer acetate therapy on functional properties of B cells from patients with relapsing-remitting multiple sclerosis

AU - Ireland, Sara J.

AU - Guzman, Alyssa A.

AU - O'Brien, Dina E.

AU - Hughes, Samuel

AU - Greenberg, Benjamin

AU - Flores, Angela

AU - Graves, Donna

AU - Remington, Gina

AU - Frohman, Elliot

AU - Davis, Laurie S

AU - Monson, Nancy L

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N2 - IMPORTANCE: This study describes what is, to our knowledge, the previously unknown effect of glatiramer acetate therapy on B cells in patients with relapsing-remitting multiple sclerosis (MS). OBJECTIVE: To determine whether glatiramer acetate therapy normalizes dysregulated B-cell proliferation and cytokine production in patients with MS. DESIGN, SETTING, AND PARTICIPANTS: Twenty-two patients with MS whowere receiving glatiramer acetate therapy and 22 treatment-naive patients with MS were recruited at The University of Texas Southwestern Medical Center MS clinic. Cell samples from healthy donors were obtained from HemaCare (Van Nuys, California) or Carter Blood Bank (Dallas, Texas). Treatment-naive patients with MS had not received any disease-modifying therapies for at least 3 months before the study. EXPOSURES: Glatiramer acetate therapy for at least 3 months at the time of the study. MAIN OUTCOMES AND MEASURES: B-cell phenotype and proliferation and immunoglobulin and cytokine secretion. RESULTS: A restoration of interleukin 10 production by peripheral B cells was observed in patients undergoing glatiramer acetate therapy as well as a significant reduction of interleukin 6 production in a subset of patients who received therapy for less than 32 months. Furthermore, proliferation in response to high-dose CD40L was altered and immunoglobulin production was elevated in in vitro-activated B cells obtained from patients who received glatiramer acetate. CONCLUSIONS AND RELEVANCE: Glatiramer acetate therapy remodels the composition of the B-cell compartment and influences cytokine secretion and immunoglobulin production. These data suggest that glatiramer acetate therapy affects several aspects of dysregulated B-cell function in MS that may contribute to the therapeutic mechanisms of glatiramer acetate.

AB - IMPORTANCE: This study describes what is, to our knowledge, the previously unknown effect of glatiramer acetate therapy on B cells in patients with relapsing-remitting multiple sclerosis (MS). OBJECTIVE: To determine whether glatiramer acetate therapy normalizes dysregulated B-cell proliferation and cytokine production in patients with MS. DESIGN, SETTING, AND PARTICIPANTS: Twenty-two patients with MS whowere receiving glatiramer acetate therapy and 22 treatment-naive patients with MS were recruited at The University of Texas Southwestern Medical Center MS clinic. Cell samples from healthy donors were obtained from HemaCare (Van Nuys, California) or Carter Blood Bank (Dallas, Texas). Treatment-naive patients with MS had not received any disease-modifying therapies for at least 3 months before the study. EXPOSURES: Glatiramer acetate therapy for at least 3 months at the time of the study. MAIN OUTCOMES AND MEASURES: B-cell phenotype and proliferation and immunoglobulin and cytokine secretion. RESULTS: A restoration of interleukin 10 production by peripheral B cells was observed in patients undergoing glatiramer acetate therapy as well as a significant reduction of interleukin 6 production in a subset of patients who received therapy for less than 32 months. Furthermore, proliferation in response to high-dose CD40L was altered and immunoglobulin production was elevated in in vitro-activated B cells obtained from patients who received glatiramer acetate. CONCLUSIONS AND RELEVANCE: Glatiramer acetate therapy remodels the composition of the B-cell compartment and influences cytokine secretion and immunoglobulin production. These data suggest that glatiramer acetate therapy affects several aspects of dysregulated B-cell function in MS that may contribute to the therapeutic mechanisms of glatiramer acetate.

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