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

Ding Chen, Monica Blazek, Sara Ireland, Sterling Ortega, Xiangmei Kong, Anouk Meeuwissen, Ann Stowe, Laura Carter, Yue Wang, Ronald Herbst, Nancy L. Monson

Research output: Contribution to journalArticle

19 Scopus citations

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 CD1dhiCD5+ 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.

Original languageEnglish (US)
Pages (from-to)4823-4832
Number of pages10
JournalJournal of Immunology
Volume193
Issue number10
DOIs
StatePublished - Nov 15 2014

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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