Journal article
Single dose of glycoengineered anti-CD19 antibody (MEDI551) disrupts experimental autoimmune encephalomyelitis by inhibiting pathogenic adaptive immune responses in the bone marrow and spinal cord while preserving peripheral regulatory mechanisms
The Journal of immunology (1950), Vol.193(10), pp.4823-4832
11/15/2014
DOI: 10.4049/jimmunol.1401478
PMCID: PMC4373313
PMID: 25281717
Abstract
Plasma cells and the autoreactive Abs they produce are suspected to contribute to the pathogenesis of multiple sclerosis, but recent attempts to target these components of humoral immunity have failed. MEDI551, an anti-CD19 Ab that depletes mature B cells including plasma cells may offer a compelling alternative that reduces pathogenic adaptive immune responses while sparing regulatory mechanisms. Indeed, our data demonstrate that a single dose of MEDI551, given before or during ongoing experimental autoimmune encephalomyelitis, disrupts development of the disease. Leukocyte infiltration into the spinal cord is significantly reduced, as well as short-lived and long-lived autoreactive CD138(+) plasma cells in the spleen and bone marrow, respectively. In addition, potentially protective CD1d(hi)CD5(+) regulatory B cells show resistance to depletion, and myelin-specific Foxp3(+) regulatory T cells are expanded. Taken together, these results demonstrate that MEDI551 disrupts experimental autoimmune encephalomyelitis by inhibiting multiple proinflammatory components whereas preserving regulatory populations.
Details
- Title: Subtitle
- Single dose of glycoengineered anti-CD19 antibody (MEDI551) disrupts experimental autoimmune encephalomyelitis by inhibiting pathogenic adaptive immune responses in the bone marrow and spinal cord while preserving peripheral regulatory mechanisms
- Creators
- Ding Chen - Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX 75390Monica Blazek - Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX 75390Sara Ireland - Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX 75390Sterling Ortega - Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX 75390Xiangmei Kong - Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX 75390Anouk Meeuwissen - Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX 75390Ann Stowe - Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX 75390Laura Carter - Department of Respiratory, Inflammation and Autoimmunity Research, MedImmune LLC, Gaithersburg, MD 20878; andYue Wang - Department of Respiratory, Inflammation and Autoimmunity Research, MedImmune LLC, Gaithersburg, MD 20878; andRonald Herbst - Department of Respiratory, Inflammation and Autoimmunity Research, MedImmune LLC, Gaithersburg, MD 20878; andNancy L Monson - Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX 75390; Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390 nancy.monson@utsouthwestern.edu
- Resource Type
- Journal article
- Publication Details
- The Journal of immunology (1950), Vol.193(10), pp.4823-4832
- DOI
- 10.4049/jimmunol.1401478
- PMID
- 25281717
- PMCID
- PMC4373313
- NLM abbreviation
- J Immunol
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Publisher
- United States
- Grant note
- R01 NS040993 / NINDS NIH HHS T32 AI005284 / NIAID NIH HHS
- Language
- English
- Date published
- 11/15/2014
- Academic Unit
- Pathology
- Record Identifier
- 9984065377102771
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