Preclinical assessment of two FcγRI-specific antibodies that competitively inhibit immune complex-FcγRI binding to suppress autoimmune responses.

ABSTRACT: Overactivation of FcγRI by immune complexes (IC) is implicated in various autoimmune disorders and neuropathies. Currently, no effective FcγRI-specific blocking antibodies are available. Here we report preclinical data revealing two anti-FcγRI antibodies, C01 and C04, with high affinity, Fab-mediated binding within the IgG binding site on extracellular domain 2 of FcγRI. Both C01 and C04 block 90% of IgG and IC binding, and displace ~60% of pre-bound ICs without activating FcγRI, thereby minimizing the risk of aggravating inflammation. In the context of autoimmunity, C01 and C04 inhibit RA patient-derived autoantibody-IC binding to monocytes, macrophages and activated neutrophils, meanwhile they also inhibit the binding of opsonized platelets to monocytes from patients with immune thromboc

SUBMITTER: Holtrop T 

PROVIDER: S-EPMC12630735 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature