Treating murine inflammatory diseases with an anti-erythrocyte antibody

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.

ROCK inhibition with Y-27632 reduces joint inflammation and damage in serum-induced arthritis model and decreases in vitro osteoclastogenesis in patients with early arthritis

“…In effect, by 10 days the affected joints are extensively damaged and inflammation subsides thereafter. Inflammation can be maintained by repeated serum transfers, but there is no evidence of additional joint destruction (63)(64)(65).…”

Network analysis indicating the pharmacological mechanism of Yunpi-Qufeng-Chushi-prescription in prophylactic treatment of rheumatoid arthritis

“…Arachidonic acid metabolism pathway was demonstrated to be relate with mechanism of tocilizumab in dealing with early RA patients [ 24 ]. Adherens junction is indispensable components of the vessel wall that affect vascular permeability [ 25 ] while activation of complement and coagulation cascades modulates synovium and systemic inflammation [ 26 ]. The enrichment results suggested that function of YQCP is closely associated with RA therapy.…”

Inhibition of platelet phagocytosis as an in vitro predictor for therapeutic potential of RBC antibodies in murine ITP

“…21 This conclusion is also supported by studies evaluating polyclonal anti-D, where responses did not correlate with erythrocyte-sensitization, hemolysis, hemoglobin, or haptoglobin levels. 6,9,10,18,19,22 We have previously shown that TER119 ameliorates ITP before signs of anemia and does not have a therapeutic effect concordant with maximal anemia, 15 indicating that anemia itself may be uncoupled from therapeutic activity. In the present work, 3 antibodies (deglycosylated TER119, CBC512, and MIMA29) induced anemia but failed to ameliorate murine ITP, suggesting that anemia itself is insufficient to ameliorate ITP by antierythrocyte antibodies.…”

“…9,10 To add to the complexity, we have recently shown that the TER119 antibody, which mimics the action of anti-D in murine ITP amelioration, [12][13][14] has anti-inflammatory effects in murine arthritis and can prevent disease activity in a murine model of transfusionrelated acute lung injury. 15 Since the spleen and the MPS are not a priori involved in the development of arthritis or transfusion-related acute lung injury, this could question the simplistic concept of MPS blockade in the therapeutic action of anti-erythrocyte antibodies.…”