
Implications of Fc Neonatal Receptor (FcRn) Manipulations for Transplant Immunotherapeutics
Author(s) -
Stanley C. Jordan,
Noriko Ammerman,
Ashley Vo
Publication year - 2020
Publication title -
transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.45
H-Index - 204
eISSN - 1534-6080
pISSN - 0041-1337
DOI - 10.1097/tp.0000000000002912
Subject(s) - neonatal fc receptor , antibody , immunology , desensitization (medicine) , immunoglobulin g , receptor , mhc class i , major histocompatibility complex , fragment crystallizable region , medicine , biology , antigen , genetics
Alloimmune injury to allografts is mediated by pathogenic donor-specific alloantibodies, usually of the IgG isotype. Currently, strategies used to reduce donor-specific alloantibodies are collectively called desensitization. Despite successes, these treatments have limited efficacy and can be associated with adverse events, infectious complications, and high cost. Fc neonatal receptor (FcRn) was originally discovered as a transport mechanism for IgG from maternal circulation to fetus. FcRn receptors are now known to be widely distributed in virtually all tissues. IgG and albumin binding to FcRn is pH-dependent, which results in a significant prolongation their half-life. Structural analysis shows FcRn is a nonclassical major histocompatibility complex Class I receptor, which is emerging as a novel target to significantly reduce the half-life of pathogenic antibodies or extend the half-life of therapeutic monoclonals. Manipulation of IgG-Fc/FcRn interactions has implications for treatment of virtually all IgG-mediated diseases. The use of monoclonals directed at the FcRn can rapidly enhance the turnover of total IgG, including pathogenic IgG. In this review, we highlight the aspects of FcRn biology responsible for development of FcRn targeted therapeutics aimed at pathogenic autoantibodies and alloantibodies. We also explore the novel modifications of therapeutic monoclonals that exploit FcRn functions to enhance therapeutic efficacy.