Autoantibodies, human Fcγ receptors, and autoimmunity
Margherita Sisto1,3, Sabrina Lisi1,3, Simona D’Amore2, Massimo D’Amore2
1Department of Human Anatomy and Histology, Cell Biology Section, 2Department of Internal Medicine and Public Medicine, Rheumatology Section, University of Bari Medical School, Bari, Italy; 3The first two authors have equal contribution in this work and both are equally considered the first authors
Abstract: Receptors for the Fc fragment of immunoglobulin G (FcγRs) represent the link between the humoral and cellular immune responses. In humans, three different types of FcγRs belonging to the immunoglobulin gene superfamily, have been identified; FcγRI (cluster of differentiation (CD64), FcγRII (CD32) and FcγRIII (CD16). FcγRs are important molecules not only to mediate and control the effectors functions of immunoglobulin G antibodies, but they also control the autoimmunity–tolerance balance in the periphery. The development of autoimmune diseases is complex and dependent on multiple genes and environmental factors. A wide range of inflammatory and autoimmune diseases such as vasculitis, glomerulonephritis, and autoimmune hemolytic anemia, seems to be mediated, in part, by FcγRs. Considering that the autoantibodies target intracellularly located antigens, recent findings supposed that, under certain conditions, FcγRs are involved in the penetration of antibodies into cells and FcγRs constitute one of the main effector mechanisms through which autoantibodies exert their action. In this review we concentrate on the role of human FcγRs in autoantibodies penetration and summarize the current knowledge on the structure, ligand-binding capacity, and their role in autoimmunity and pathogenic effect of autoantibodies. These novel insights into antibody FcR interactions might be useful to produce the next generation of improved immunotherapeutic molecules.
Keywords: autoantibodies, FcγReceptors, IgG, adalimumab, salivary gland
This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.Download Article [PDF]