Antibodies reacting with surface and intracellular antigen determinants of endothelial cells (EC) have been detected in the sera of patients with vasculitis (178-183). The EC antigens can be constitutively expressed, and/or modulated by cytokines, or cryptic. In addition, antigen determinants for AECA may also be molecules that adhere to EC (184). However, many AECA antigens are currently not well characterized. The target antigens remain to be identified. In a recent study it could be shown that small portions of AECA are directed against cardiolipin (178). Although sera from APS patients prolonged coagulation tests, eluted EC membrane-bound antibodies do not affect coagulation, suggesting that AECA may belong to antiphospholipid antibodies subsets that does not interfere with coagulation. AECA shown to be antiphospholipid antibodies may bind to bGP-1 attached to the EC membrane.
Usually, AECA are detected by cell ELISA using human umbilical vein EC as the antigen source. Alternative methods include RIA, indirect immunofluorescence technique [slides as well as fluorescent-activated cell sorter (FACS)] or Western blot. However, none of these techniques has been sufficiently standardized. Microvascular EC, which would represent a more clinically relevant substrate, are not available in sufficient numbers for AECA determination.
AECA have been observed in sera from many primary (Kawasaki syndrome, Wegener’s granulomatosis, etc.) and secondary vasculitides (vasculitis associated with RA, SLE, etc.) (185-190). Although probably of limited value in disease diagnosis, the detection of these antibodies may be valuable in several disease activity (181, 188, 191).
In several diseases such as SLE and systemic vasculitis, high AECA titers are found during active disease whereas lower titers or disappearance of AECA have been reported during remission. The correlation between changes in AECA titers and disease activity suggests an important role for AECA in processes in which vessel wall damage occurs, although it does not exclude the possibility that AECA are an epiphenomenon of vascular injury. Several recent in vitro studies support a role of AECA in the pathophysiology of these inflammatory disorders (184, 188-191). AECA may play a role in the pathophysiology by inducing activation of EC resulting in upregulation in the expression of endothelial adhesion molecules and/or secretion of chemoattractants and cytokines (179, 184, 188). An alternative mechanism by which AECA could be a trigger in the pathogenesis of some diseases is complement dependent cytotoxicity (CDC) and/or antibody dependent cellular cytotoxicity (ADCC) (184-186, 192, 193).