Classification of anti-endothelial cell antibodies into antibodies against microvascular and macrovascular endothelial cells: The pathogenic and diagnostic implications

Antiendothelial cell antibodies mediate enhanced leukocyte adhesion to cytokine-activated endothelial cells through a novel mechanism requiring cooperation between FcγRIIa and CXCR1/2

“…[2][3][4][5] The capacity of endothelial cells (ECs) to support these interactions with PMNs is stimulated by cytokines such as TNF␣ and IL-1␤, which induce expression of a large number of adhesion molecules, chemottractant, and other proinflammatory genes, including E-selectin, chemokines (eg, IL-8), and ICAM-1. 6,7 Antibodies that react with the surface of vascular endothelial cells (antiendothelial cell antibodies, AECAs) are found in a variety of diseases associated with vascular injury, including systemic lupus erythematosus (SLE), systemic sclerosis, Takayasu arteritis, Wegener granulomatosis, Behçets syndrome, and transplant arteriosclerosis, 8,9 A number of mechanisms have been proposed whereby IgG binding to ECs may exert pathogenic effects, including the induction of EC inflammatory activation and thrombogenicity, the stimulation of leukocyte free-radical production and cellular cytotoxicity, and the induction of EC apoptosis. [10][11][12][13][14] Interactions between circulating human PMNs and immune complexes are mediated via 2 low-affinity Fc␥ receptors, Fc␥RIIa (CD32a) and Fc␥RIIIb (CD16b), which are both thought to form homodimers and have distinct membrane-anchoring and -signaling capacities.…”

Pre-transplant serum concentrations of anti-endothelial cell antibody in panel reactive antibody negative renal recipients and its impact on acute rejection

“…It is now clear that vascular endothelial cells are heterogeneous, include macro-and microvasculature, exhibit tissue-specific differences and different pathogenic significance (22). There are differences in antigen composition and reactions to stimuli between the endothelium from large and small vessels, and between endothelial cells derived from various microvascular endothelial beds (23).…”

Angiotensin II Type 1–Receptor Activating Antibodies in Renal-Allograft Rejection

“…21,22 However, research on anti-endothelial-cell antibodies is hampered by the heterogeneity of endothelial cells in various vascular beds, a fact that makes identifying a standard detection method difficult. 23 Moreover, initially detected target antigens of anti-endothelialcell antibodies were of unclear relevance. 23 We suggest that AT 1 -receptor antibodies have similarities to anti-endothelial-cell antibodies since endothelial cells have one AT 1 receptor, 24 and AT 1 -receptor antibodies induced phosphorylation of ERK 1/2 in endothelial cells.…”

“…23 Moreover, initially detected target antigens of anti-endothelialcell antibodies were of unclear relevance. 23 We suggest that AT 1 -receptor antibodies have similarities to anti-endothelial-cell antibodies since endothelial cells have one AT 1 receptor, 24 and AT 1 -receptor antibodies induced phosphorylation of ERK 1/2 in endothelial cells. We further suggest that binding of AT 1 -receptor antibodies to the AT 1 receptor is a critical step for activating the downstream signaling cascade, mimicking the action of angiotensin II and inducing damage to the allograft.…”