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Sci Transl Med. 2019 Aug 21;11(506). pii: eaau8217. doi: 10.1126/scitranslmed.aau8217.

Treating murine inflammatory diseases with an anti-erythrocyte antibody.

Crow AR1,2,3, Kapur R1,2,3,4,5, Koernig S6, Campbell IK6, Jen CC2,3, Mott PJ2,3, Marjoram D2,3, Khan R2,3, Kim M2,3, Brasseit J7, Cruz-Leal Y1,2,3, Amash A2,3, Kahlon S2,3, Yougbare I1,2,3, Ni H1,2,3,8,9,10, Zuercher AW7, Käsermann F7, Semple JW1,2,3,4,8,9,11, Lazarus AH12,2,3,8,9.

Author information

1
Canadian Blood Services Centre for Innovation, Ottawa, Ontario K1G 4J5, Canada.
2
Department of Laboratory Medicine and Keenan Research Centre for Biomedical Science of St. Michael's Hospital, University of Toronto, Toronto, Ontario M5B 1W8, Canada.
3
Toronto Platelet Immunobiology Group, Toronto, Ontario, M5B 1T8 Canada.
4
Department of Hematology and Transfusion Medicine, Lund University, Lund 221 84, Sweden.
5
Department of Experimental Immunohematology, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, 1066 CX Amsterdam, Netherlands.
6
CSL Limited, Bio21 Institute, University of Melbourne, Parkville, Victoria 3010, Australia.
7
CSL Behring, Research, CSL Biologics Research Center, Bern, Switzerland.
8
Department of Medicine, St. Michael's Hospital, University of Toronto, Toronto, Ontario M5B 1W8, Canada.
9
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
10
Department of Physiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
11
Department of Pharmacology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
12
Canadian Blood Services Centre for Innovation, Ottawa, Ontario K1G 4J5, Canada. lazarusa@smh.ca.

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.

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