The collagen‐like component of the complement system, C1q, is recognized by 7 S autoantibodies and is functionally impaired in synovial fluids of patients with rheumatoid arthritis

Abstract

Cross‐reactivity between type II collagen (CII) and C1q, the collagen‐like subunit of the first component of complement, has been demonstrated in synovial fluid (SF) from rheumatoid arthritis (RA) patients. Many authors have studied autoimmunity to CII in RA, but little work has been done on autoimmunity to C1q in RA. In the data presented here, we have been able to show that in addition to native C1q, an altered form of C1q is present in SF from RA patients. Furthermore, a low molecular weight form of C1q is present in RA SF, although its role, if any, in the pathogenesis of RA is unclear. The presence in these RA SF of C1q‐specific antibodies (IgG and IgM) has been studied and we have partially characterized the antibody moieties involved. As well as binding to C1q and fragments representing the collagen‐tails from C1q, 7 S IgG autoantibodies against C1q also bind to a C1q molecule altered in vitro by incubation with reactive oxygen species and to the non‐apeptide KGEQGEPGA (representing residues 26–34 from the C1q A‐chain), which has previously been shown to suppress the onset of CII‐induced arthritis in an animal model.

Autoantibody Patterns in Synovial Fluids from Patients with Rheumatoid Arthritis or Other Arthritic Lesions

“…Few SF samples were positive for antibodies against anti-C1q, corresponding well with another study of SF [33] and of serum [34]. However, it cannot be excluded that these antibodies exist more frequently, but are bound in immune complexes and are therefore not detectable in the assay [33].…”

“…However, it cannot be excluded that these antibodies exist more frequently, but are bound in immune complexes and are therefore not detectable in the assay [33]. Anti-DNA antibodies were also found in few SF samples and were correlated with high total immunoglobulin levels, implicating non-specific binding of antibodies to DNA.…”

Autoantibodies against C1q: view on clinical relevance and pathogenic roles

“…A third pitfall in the measurement of IgG C1qAb may be recognition of C1q by anti‐collagen antibodies. Proteolysis by collagenase or exposure to oxidation of C1q may reveal epitopes on the collagen‐like region of C1q that also occur on collagen type II [29, 30]. IgG autoantibodies to collagen have been demonstrated to be present in serum of SLE patients [31].…”

Humoral autoreactivity directed against surfactant protein-A (SP-A) in rheumatoid arthritis synovial fluids

“…IgG and IgA autoantibodies reactive with C1q‐CR have been detected in the sera of patients with rheumatoid vasculitis [15], and IgG autoantibodies against C1q‐CR are believed to play a role in nephritis in patients with systemic lupus erythematosus (SLE) [16–18]. IgG autoantibodies reactive with C1q‐CR have also been identified in patients with hypocomplementaemic urticarial vasculitis syndrome (HUVS) [19] and we have recently identified both IgG and IgM autoantibodies reactive with C1q‐CR, as well as C1q in an altered (oxidized) form [8] in the SF from patients with RA. In a recent report, Dobbie and co‐workers revealed the presence of SP‐A, associated with lamellar bodies, in synoviocytes from the joints of patients with RA [6].…”

“…Goat anti‐human C1q was raised in the Institute’s animal facility using standard procedures. This antibody has been shown by Western blotting to bind specifically to the A, B, and C chains of C1q, including C1q present in SF [8]. Rabbit anti‐human SP‐A was kindly donated by K. B. M. Reid (MRC Immunochemistry Unit, Oxford, UK).…”