C3 Activation Products, C3 Containing Immune Complexes, the Terminal Complement Complex and Native C9 in Patients with Rheumatoid Arthritis

Abstract

Complement activation products, C9 and C3-containing circulating immune complexes (CIC), were evaluated in plasma and synovial fluid (SF) from patients with rheumatoid arthritis (RA) and osteoarthritis. C3 activation products and the fluid phase terminal complement complex were considerably elevated in SF from RA patients reaching levels five- to eighttimes that in plasma, consistant with a local activation of the whole cascade in the joints. The results emphazise the importance of detecting C3 activation by neoepitope expression instead of single fragment determinations. The concentration of native C9 was lower in synovial fluid compared with plasma, consistant with the excessive local complement activation. Increased CIC levels which correlated with the degree of complement activation were also found in the SF from the RA patients.

Organ Messenger Ribonucleic Acid and Plasma Proteome Changes in the Adjuvant-Induced Arthritis Model: Responses to Disease Induction and Therapy with the Estrogen Receptor-β Selective Agonist ERB-041

“…We observed peptides representing both complement C3 and C9 increase, which is consistent with increases in C3-and C9-containing circulating immune complexes in serum and synovial fluid of RA patients (45). Both the ␣-and ␤-chains of fibrinogen increase in the rat model plasma.…”

Circulating Immune Complexes among Diabetic Children

“…Individuals with juvenile onset Type 1 diabetes mellitus are at a high risk for the development of diabetic microangiopathy and vascular disease (Linderkamp et al, 1999). Similar studies on the quantitation of CIC levels have been conducted on a variety of autoimmune disease including systemic sclerosis (Stanilova and Slavov, 2003), SLE and rheumatoid arthritis (Ö lmez et al, 1991;Stanilova and Slavov, 2001). Type 1 diabetes mellitus is also an autoimmune disease in which different types of autoantibodies have been identified such as those against beta cells (insulin-autoantibodies, islet cell-autoantibodies, GAD autoantibodies (Verge et al, 1998)) and antibodies against vascular wall proteins such as elastin (Nicoloff et al, 2000b) and collagen (Nicoloff et al, 2002).…”

A Role for Complement in Antibody-Mediated Inflammation: C5-Deficient DBA/1 Mice Are Resistant to Collagen-Induced Arthritis

“…A significant role for complement in the pathologic inflammatory process in RA is supported by a variety of molecular and pathologic evidence (45)(46)(47)(48)(49)(50)(51)(52)(53). First, extensive local complement activation has been clearly demonstrated in synovial tissue and the synovial fluid of affected joints of patients with RA.…”

“…As a result, total hemolytic complement, C3, and C4 are markedly diminished in synovial fluid relative to total protein concentration. Measurement of the activated proinflammatory complement byproducts that are generated after C5 cleavage, C5a and C5b-9, has also shown significant elevations in RA joints (45)(46)(47)(48)(49)(50)(51)(52)(53). C5a and C5b-9 can mediate multiple proinflammatory activities, including leukocyte chemotaxis, adhesion molecule up-regulation, cellular activation with consequent release of additional mediators, and cell lysis (30).…”