To characterize the putative target
antigens for antiendothelial cell
antibodies (
AECA), the possible pathophysiological role of
AECA, and the clinical value of these
antibodies as markers of disease activity.
METHODS: A structured literature search was done using Medline in combination with a manual search. Two physicians reviewed all articles of special interest.
RESULTS:
AECA are a heterogenous group of
antibodies directed against a variety of
antigen determinants on endothelial cells (EC). The EC
antigens can be constitutively expressed, constitutively expressed and modulated by
cytokines, or cryptic. In addition,
antigen determinants for
AECA may also be molecules that adhere to EC ("planted"
antigens). However, many
AECA antigens are currently not well characterized.
AECA are detected in a wide variety of inflammatory disorders. Although probably of limited value in disease diagnosis, the detection of these
antibodies may be valuable in following disease activity. In several diseases such as
systemic lupus erythematosus and
systemic vasculitis, high
AECA titers are found during active disease whereas lower titers or disappearence 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.
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. 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). In experimental animal models,
antibodies to
antigenic determinants expressed on EC were capable of inducing
vascular injury.
CONCLUSION:
AECA represent a heterogenous group of
antibodies directed against a variety of
antigenic determinants on EC. They are present in a variety of inflammatory disorders. The detection of these
antibodies may be valuable in following disease activity. Further characterization of putative
antigens is needed to better understand their pathophysiological role.