Complement in the Initiation and Evolution of Rheumatoid Arthritis

• Published in: Frontiers in immunology Vol. 9; p. 1057
• Main Authors: Holers, V Michael, Banda, Nirmal K
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 28.05.2018
• Subjects: alternative pathway; Animals; arthritis; Arthritis, Rheumatoid - immunology; Arthritis, Rheumatoid - metabolism; Biomarkers; classical pathway; complement; Complement Activation - immunology; Complement System Proteins - immunology; Complement System Proteins - metabolism; Disease Models, Animal; Disease Susceptibility; Humans; Immunology; Inflammation Mediators - metabolism; lectin pathway; mannose-binding protein-associated serine proteases; Mice; Protein Processing, Post-Translational; alternative pathway; classical pathway; arthritis; inflammation; mannose-binding protein-associated serine proteases; complement; lectin pathway
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2018.01057

The complement system is a major component of the immune system and plays a central role in many protective immune processes, including circulating immune complex processing and clearance, recognition of foreign antigens, modulation of humoral and cellular immunity, removal of apoptotic and dead cells, and engagement of injury resolving and tissue regeneration processes. In stark contrast to these beneficial roles, however, inadequately controlled complement activation underlies the pathogenesis of human inflammatory and autoimmune diseases, including rheumatoid arthritis (RA) where the cartilage, bone, and synovium are targeted. Recent studies of this disease have demonstrated that the autoimmune response evolves over time in an asymptomatic preclinical phase that is associated with mucosal inflammation. Notably, experimental models of this disease have demonstrated that each of the three major complement activation pathways plays an important role in recognition of injured joint tissue, although the lectin and amplification pathways exhibit particularly impactful roles in the initiation and amplification of damage. Herein, we review the complement system and focus on its multi-factorial role in human patients with RA and experimental murine models. This understanding will be important to the successful integration of the emerging complement therapeutics pipeline into clinical care for patients with RA.