C5 and rheumatoid arthritis: Complement has been implicated in disease progression in arthritis; biomarkers of complement are elevated circulating in blood and in synovial tissues of patients with rheumatoid arthritis, and genetic deficiencies in receptors for C3a, C5a, or C6 protein all reduce disease severity in mice.8,127,168 However, it is not yet clear if the complement system contributes directly to joint pain.