154 - Systemic Vasculitis Autoantibodies Targeting Endothelial Cells

Summary

The vasculitides are defined by the presence of leukocytes in the vessel wall, producing reactive damage to mural structures. Compromise of the lumen leads to tissue ischemia and necrosis. In general, affected vessels vary in size, type, and location in association with the specific vasculitic disorder. In recent years, substantial progress has been made in identifying the attributes of specific types of vasculitis, thus allowing for accurate diagnosis. One approach to classifying vasculitides categorizes them, in part, on the basis of the predominant type of vessel affected (Table 154–1). Accordingly, vasculitides are classified into large-vessel vasculitis, medium-sized vessel vasculitis, and small-vessel vasculitis. Large-vessel vasculitis primarily affects the aorta and its primary branches, but medium-sized arteries may also be affected. Medium-sized vessel vasculitis is a disease of small and medium-sizedmuscular arteries. Small-vessel vasculitis affects vessels smaller than arteries, such as arterioles, venules, and capillaries. It is important to note that small-vessel vasculitis sometimes also affects arteries, and thus the vascular distribution overlaps.

The exact mechanisms underlying these disorders are unclear. Three different pathogenic models of disease have been advanced to help explain why the lesions of a particular vasculitic syndrome are found only in specific vessels. First, the distribution of the antigen responsible for the vasculitis may be differentially distributed. Second, the recruitment and accumulation of the inflammatory infiltrate is likely to be determined by site-specific properties of the endothelial cell (EC), including the expression of adhesion molecules, the secretion of mediators, peptides and hormones, and the specific interactionwith inflammatory cells. Finally, nonendothelial structures of the vessel wallmay be involved in controlling regional inflammatory processes. All three mechanisms are likely to contribute to the site-specific nature of endothelial injury and vasculitis.