Antiphospholipid syndrome is an autoimmune disease defined by the presence of
antiphospholipid antibodies in the plasma of patients with venous or arterial thrombosis
and/or recurrent pregnancy complications. Patients with antiphospholipid syndrome suffer
from increased risk of atherosclerosis and consequentially, cardiovascular diseases are now
counted among the leading causes of death worldwide.
Our aim was to examine the effect of high avidity antibodies to β2-glycoprotein I on the
secretion of inflammatory molecules from human coronary artery endothelial cells cultured
in vitro. Antibodies to β2-glycoprotein I were isolated from the imunoadsorption sample of
a patient with antiphospholipid syndrome. Their activities were compared to the activities
of an antibody fraction isolated from healthy blood donors. Resting and pre-stimulated
cells with acute-phase protein Serum Amiloid A were exposed to the indicated samples of
antibodies. After twenty hours, activation of endothelial cells was quantitatively evaluated
by determining the released concentrations chemokines, cytokines and adhesion molecules
using specific enzyme-linked immunosorbent assay.
Human coronary artery endothelial cells that were stimulated with antibodies to β2-
glycoprotein I from the patient with antiphospholipid syndrome were increasingly
excreting Monocyte chemotactic protein-1 as compared with antibodies of class G of
healthy blood donors. Also, the concentration of this chemokine was markedly increased
by prior stimulation of the cells with Serum Amiloid A. Addition of patient antibodies led
to higher concentrations of both Interleukin-8 and Interleukin-6, while only the
concentration of Interleukin-6 increased in proportion to the applied concentrations of
added Serum Amyloid A. Following the addition of the indicated samples of antibodies we
have measured comparable concentrations of the Intercellular adhesion molecule-1. In
regard to the release of Vascular cell adhesion molecule-1, the addition of anti-β2-
glycoprotein antibodies from the patient, has caused a dampening effect, which was not
observed when cells were pre-stimulated with Serum Amiloid A.
We have found that high avidity β2-glycoprotein I antibodies stimulate secretion of
chemokines, cytokines and adhesive molecules and inhibit the secretion of vascular cell
adhesion molecule-1. The effect is more intense when the inflammatory process already
existed. Antibodies to β2-glycoprotein I influence the development of atherosclerosis in
patients with antiphospholipid syndrome via induced secretion of inflammatory molecules.
|
