Autoantibodies Against dsDNA Modulate Contraction of Blood Clots

Abstract

The degree and rate of clot contraction (retraction) in systemic lupus erythematosus (SLE) patients, especially in those with a high level of anti-double stranded DNA (dsDNA) antibodies in the blood, was significantly reduced compared to healthy donors. We hypothesized that this effect was caused by the anti-dsDNA antibodies. To test this assumption, we investigated the kinetics of blood clot contraction in vitro in the absence and presence of anti-dsDNA antibodies purified from the blood serum of SLE patients. The degree of clot contraction was increased immediately after addition of the anti-DNA antibodies in a concentration-dependent manner. This stimulating effect was abrogated by a monoclonal antibody against the platelet Fc-receptor. On the contrary, after prolonged incubation (for hours) of the blood samples with the anti-DNA antibodies, the extent of clot contraction was significantly reduced. These results suggest that anti-dsDNA antibodies in SLE induce Fc-receptor-mediated chronic platelet hyperactivation, resulting in platelet exhaustion and dysfunction, including reduced contractility. The impaired contraction of blood clots and thrombi caused by autoantibodies may be an important pathogenic mechanism that affects the course and outcomes of thrombotic complications in SLE.