Levels of lectin pathway proteins in plasma and synovial fluid of rheumatoid arthritis and osteoarthritis

Abstract

The innate immune system contributes to the development of rheumatoid arthritis (RA). A potent contributor to such processes is the complement system. The complement system is known to be activated in the inflammatory phases of osteoarthritis (OA). The lectin pathway of the complement system is activated through the recognition of pathogens or altered self-structures by mannan-binding lectin (MBL) or one of the three ficolins in collaboration with MBL-associated serine proteases (MASPs). We assessed the lectin pathway in plasma and synovial fluid (SF) of 27 RA patients and 30 OA patients by measuring MBL, MASP-2, MASP-3, M-ficolin, and H-ficolin. The concentration for all 5 proteins was significantly higher in plasma than in SF (P < 0.001) and the concentration in paired plasma and SF samples correlated in both RA and OA (significance levels between <0.001 and 0.02). The ratio of SF/plasma concentration was for all proteins significantly elevated in RA compared with OA patients (all P < 0.001). The M-ficolin concentration correlated with the neutrophils in both plasma (P = 0.01) and SF (P < 0.001) of RA, and in plasma of 78 controls (P = 0.03). To our knowledge, this is the first report on these proteins in SF, except for MBL where our results are in contrast to the one previous publication. The results support an important physiological role of the neutrophils in determining the M-ficolin levels in both RA and healthy adults. We suggest that quantifications of white blood cells should be included in future clinical investigations of M-ficolin.

Immunopathogenesis of osteoarthritis

“…Doherty et al found C3 activation to be associated with RA and gout but not with OA [25]. A recent study looking specifically at the levels of lectin pathway proteins found a significant association of the level of these proteins in plasma and synoial fluid (SF) with RA and OA [26]. Several proteomic studies have identified components of complement system as differentially expressed proteins in synovial fluid [27,28], serum [29] and cartilage [30] samples from OA patients.…”

Deconstructing the Lectin Pathway in the Pathogenesis of Experimental Inflammatory Arthritis: Essential Role of the Lectin Ficolin B and Mannose-Binding Protein–Associated Serine Protease 2

“…Among other factors, it is now appreciated that the complement system plays an important role in the pathogenesis of RA. Complement activation is essential for disease progression in passive transfer mouse models of RA, and complement fragments derived from the activation process have been found in the synovium of RA patients (5–7). Furthermore, complement-directed therapeutics have shown excellent efficacy in mouse models of RA such as collagen antibody-induced arthritis (CAIA) (8, 9).…”

Production of complement components by cells of the immune system

“…Moreover, the terminal pathway components C5, C6, C7, C8 and C9 are secreted, which are able to assemble as MAC [24,65]. For the recognition molecules of the LP there is less evidence of local production by monocytes; however, it was shown that monocytes have intracellular M-ficolin and in synovial fluid of RA patients there was a correlation between M-ficolin and the total number of blood monocytes [42,66]. Several control proteins are also secreted by cultured monocytes, such as FH, FI, C4BP and C1INH [59,62,67].…”