Treating murine inflammatory diseases with an anti-erythrocyte antibody

Abstract

An anti-erythrocyte antibody redirects inflammation in multiple mouse models. Fighting inflammation with inflammation Immune thrombocytopenia (ITP) can be treated with IVIg or even anti-D, which is immunoglobulin directed against red blood cells (RBCs). To investigate whether an anti-RBC antibody could confer benefits in other inflammatory models, Crow et al. turned to the mouse anti-RBC antibody Ter119, known to be not only inflammatory but also therapeutic in ITP models. They now show that the beneficial effects in ITP are not due to induction of anemia. Ter119 also successfully treated multiple mouse models of arthritis and prevented symptoms in an acute lung injury model. These effects were dependent on a functional Fc portion and involved modulation of monocytes and chemokines. Their results suggest that anti-RBC antibodies might be able to replace IVIg for many inflammatory indications. 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.