The prospects for targeting FcR as a novel therapeutic strategy in rheumatoid arthritis.

Abstract

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by synovial membrane hyperplasia, infiltration of inflammatory cells and bone tissue destruction. Although there have been many measures taken for RA therapy in recent years, they are not sufficiently safe or effective. Thus, it is very important to develop new drugs and slow down damage to other healthy organs in the case of RA. Lately, immunoglobulin Fc receptors (FcRs), such as the IgG Fc receptor (FcγR), IgA Fc receptor (FcαR), and IgD Fc receptor (FcδR), have been found to be involved in inducing or suppressing arthritis. FcRs interacting with immune complexes (ICs) are a key factor in the etiopathogenesis of RA. Therefore, an increasing number of methodsfor the targeted treatment of RA with FcRs are emerging, such as recombinant soluble FcγRs, recombinant multimeric Fc fragments and monoclonal antibodies, and have been demonstrated to significantly improve RA symptoms. Simultaneously, certain kinases involved in the downstream signaling of FcRs can also be a target for the treatment of RA, such as Syk and Btk inhibitors. An overview of these FcRs is provided in this review, including a description of FcR-related functions, signaling pathways, and potential FcR-targeting molecules for RA therapy. To date, the initial results of those developed FcR-targeting molecules have been promising. With this, FcRs might offer a better alternative to RA medication. Additionally, further pharmacological characterization and a better understanding of the unique mechanisms of FcR-targeting molecules are necessary.

• Authors: Yujing Wu, Wenwen Pan, Xiaoxi Hu, Aijun Zhang, Wei Wei
• Journal: Biochemical pharmacology (Biochem Pharmacol) Vol. 183 Pg. 114360 (01 2021) ISSN: 1873-2968 [Electronic] England
• PMID: 33301760 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

• Antirheumatic Agents
• Receptors, Fc

Topics

• Animals
• Antirheumatic Agents (administration & dosage, metabolism)
• Arthritis, Rheumatoid (drug therapy, immunology, metabolism)
• Drug Delivery Systems (methods, trends)
• Humans
• Receptors, Fc (antagonists & inhibitors, immunology, metabolism)
• Signal Transduction (drug effects, physiology)