Platelets as target cells in rheumatoid arthritis and systemic lupus erythematosus: A platelet specific immunoglobulin inducing the release reaction

Abstract

Sera from patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) were assessed for in vitro platelet activation as measured by serotonin release; 24% (30) of 124 tested RA sera and 51% (35) of 69 SLE sera induced a significant 3H serotonin release. Investigation of 17 synovial fluid samples from RA patients revealed significant release in 82%. Concomitant testing for lymphocytotoxic antibodies and immune complexes did not show any correlation to platelet activation. Upon gel filtration the release-inducing activity of positive sera was localized in the region of 160 000 Daltons. Further characterization by ion exchange chromatography, immune electrophoresis, chromatographic and SDS PAGE molecular weight determinations, as well as analytical ultracentrifugation all confirmed the IgG nature of the release-inducing protein. Negative blocking experiments performed by preincubation of platelets with Fc-IgG fragments prior to challenge with a release-inducing serum excluded the participation of Fc receptors in the reaction. It was concluded that the release was caused by a platelet reactive IgG antibody. This antibody may also cause release of platelet mediators in vivo and may thus contribute to the pathogenesis of the generalized vasculopathy in both diseases.

Studies on the Binding of Proteins to the Human Platelet Surface: Relation to Platelet Activation

“…This possibility suggested is supported by observations discussed by Pfueller and Liischer (38). Studies by Weissbarth et al (39) indicate that the same sequences may also occur in nonthrom bocytopenic patients with SLE. In the same report, the authors demonstrated the presence of an anti-platelet IgG antibody in the sera both from RA and SLE patients, and the antibody was observed to induce serotonin release from normal platelets (39).…”

“…Studies by Weissbarth et al (39) indicate that the same sequences may also occur in nonthrom bocytopenic patients with SLE. In the same report, the authors demonstrated the presence of an anti-platelet IgG antibody in the sera both from RA and SLE patients, and the antibody was observed to induce serotonin release from normal platelets (39). The formation of platelet aggregates in RA and SLE can therefore be caused by a cooperative effect of IgG-containing immune complexes and platelet antibody.…”

Clinical Characteristics of Secondary Immune Thrombocytopenia Associated With Primary Sjögren's Syndrome

“…Pathogenetic mechanisms of primary ITP comprise both, autoantibody-(such as autoantibodies to platelet and thrombopoietin) and T cell-mediated immune responses (13). A study reported that platelet destruction was part of an immune complex-mediated destruction of the reticulo-endothelial system in SLE (14). It has been suggested that elevated plasma P-selectin autoantibodies might play a role in the pathogenesis of ITP in pSS patients (15).…”