Fc-gamma receptors: Attractive targets for autoimmune drug discovery searching for intelligent therapeutic designs

Autoantibody immune complexes (ICs) mediate pathogenesis in multiple autoimmune diseases via direct interference with target function, complement fixation, and interaction with Fc-gamma receptors (Fc gamma Rs). Through high avidity interactions, ICs are able to crosslink low affinity Fc gamma Rs expressed on a wide variety of effector cells, leading to secretion of pro-inflammatory mediators and inducing cytotoxicity, ultimately resulting in tissue injury. Given their relevance in numerous autoimmune diseases, Fc gamma Rs have been considered as attractive therapeutic targets for the last three decades. However, a limited number of investigational drug candidates have been developed targeting Fc gamma Rs and only a few approved therapeutics have been associated with impacting Fc gamma Rs. This review provides a historical overview of the different therapeutic approaches used to target Fc gamma Rs for the treatment of autoimmune and inflammatory diseases. (C) 2016 Elsevier B.V. All rights reserved.