The influence of anti-fibronectin antibodies on interactions involving extracellular matrix components and cells: a possible pathogenic mechanism

Abstract

SUMMARYAntibodies, directed to the 30-kD collagen binding domain (CBD) of fibronectin (Fn), have been previously demonstrated in sera from patients with systemic lupus erythematosus (SLE), and we now investigate the possible pathogenic effects of these antibodies on collagen-Fn and cell-Fn interactions. The binding of type I collagen to Fn was demonstrated by ELISA, and could be specifically inhibited by the preincubation of solid-phase immobilized Fn with anti-Fn antibodies from SLE sera. By using indirect immunofluorescent staining, anti-Fn antibody containing SLE sera but not normal human serum (NHS) reduced the deposition of newly synthesized collagen and Fn on living human skin fibroblasts. We also found that sera from SLE patients containing anti-Fn antibodies significantly reduced thyroid cell attachment to Fn immobilized on plastic compared with NHS. These effects were shown to be due to the presence of anti-Fn antibodies in these sera, as SLE sera depleted of anti-Fn antibodies did not reduce the deposition of collagen or Fn on cultured fibroblasts, nor did they inhibit cell attachment.

Autoantibodies Directed to Extracellular Matrix Components in Patients With Different Clinical Forms of Periodontitis

“…These changes could result from the damage of such proteins by an ongoing disease process and/or by an interaction with macromolecules. 38 Our results indicate that patients with AgP produce autoantibodies directed to components of ECM. As shown in Table 3, the values of 62.5%, 66.7%, and 82.3% of sera positive for anti-type I collagen, anti-fibronectin, and anti-laminin, respectively, suggest that an autoimmune response is necessary to determine a degree of participation of autoantibodies in the genesis and maintenance of AgP.…”

“…It is likely that their production is induced as a consequence of tissue damage resulting in the release of large amounts of those immunoglobulins into the bloodstream and/or a consequence of alterations in protein molecules of damaged tissues leading to an exposure of novel immunogenic epitopes. These changes could result from the damage of such proteins by an ongoing disease process and/or by an interaction with macromolecules 38 . Our results indicate that patients with AgP produce autoantibodies directed to components of ECM.…”

Fibronectin Autoantibodies

“…In SLE, AFA might block the collagen-binding domain of fibronectin and the binding to C1q, which could inhibit the opsonation mediated by fibronectin and reduce immune complex clearance [11]. Fibronectin specifically interacts with Ig complexes and hence might perpetuate immune complex deposition [12].…”