Treating murine inflammatory diseases with an anti-erythrocyte antibody

Research output: Contribution to journalArticle

Abstract

Treatment of autoimmune and inflammatory diseases typically involves immune suppression. In an opposite strategy, we show that administration of the highly inflammatory erythrocyte-specific antibody Ter119 into mice remodels the monocyte cellular landscape, leading to resolution of inflammatory disease. Ter119 with intact Fc function was unexpectedly therapeutic in the K/BxN serum transfer model of arthritis. Similarly, it rapidly reversed clinical disease progression in collagen antibody-induced arthritis (CAIA) and collagen-induced arthritis and completely corrected CAIA-induced increase in monocyte Fcγ receptor II/III expression. Ter119 dose-dependently induced plasma chemokines CCL2, CCL5, CXCL9, CXCL10, and CCL11 with corresponding alterations in monocyte percentages in the blood and liver within 24 hours. Ter119 attenuated chemokine production from the synovial fluid and prevented the accumulation of inflammatory cells and complement components in the synovium. Ter119 could also accelerate the resolution of hypothermia and pulmonary edema in an acute lung injury model. We conclude that this inflammatory anti-erythrocyte antibody simultaneously triggers a highly efficient anti-inflammatory effect with broad therapeutic potential.

Details

Authors
  • Andrew R. Crow
  • Rick Kapur
  • Sandra Koernig
  • Ian K. Campbell
  • Chao Ching Jen
  • Patrick J. Mott
  • Danielle Marjoram
  • Ramsha Khan
  • Michael Kim
  • Jennifer Brasseit
  • Yoelys Cruz-Leal
  • Alaa Amash
  • Simrat Kahlon
  • Issaka Yougbare
  • Heyu Ni
  • Adrian W. Zuercher
  • Fabian Käsermann
  • John W. Semple
  • Alan H. Lazarus
Organisations
External organisations
  • Canadian Blood Services
  • Saint Michael's Hospital
  • Toronto Platelet Immunobiology Group
  • University of Amsterdam
  • CSL Behring, Switzerland
  • University of Toronto
  • University of Melbourne
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Immunology in the medical area
Original languageEnglish
Article numbereaau8217
JournalScience Translational Medicine
Volume11
Issue number506
Publication statusPublished - 2019 Aug 21
Publication categoryResearch
Peer-reviewedYes