Specificity, pathogenecity, and clinical value of antiendothelial cell antibodies

Abstract

Objective: 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.