Anti‐endothelial cell antibodies in primary antiphospholipid syndrome and SLE: patterns of reactivity with membrane antigens on microvascular and umbilical venous cell membranes

Abstract

Although there has been recent emphasis on autoantibodies to epitopes on beta-2-glycoprotein I and prothrombin in the pathogenesis of antiphospholipid syndrome (APS), antibodies other than those directed toward epitopes on phospholipid binding proteins are present. These include those reactive with antigens on platelet membrane glycoproteins, and with vascular endothelial cell membrane. As the pathogenesis of the thrombotic manifestations of APS remains unexplained, further characterization of these antibodies may be informative. We have confirmed anti-endothelial cell binding to a range of cell membrane antigens in systemic lupus erythematosus (SLE) and primary APS. Furthermore, differences in both the pattern of antibody binding and band intensity between human umbilical vein (HUVEC) and human microvascular endothelial cells (HMEC-1) were demonstrated. Of 17 primary APS sera, antibody binding to HUVEC cell membranes was found in nine and to HMEC-1 membranes in seven. Binding at 72-79 kD was confined to HUVEC. In 32 SLE sera, binding to HUVEC and HMEC-1 membranes was detected in 17 and 22 respectively, binding at 135-155 kD being confined to HMEC-1. These results are consistent with the phenotypic variation in endothelial cells of different origins and confirm the frequent presence of autoantibodies reactive with vascular endothelium in both SLE and PAPS. Whether these antibodies could be involved in the pathogenesis of thrombosis, through induction of endothelial cell apoptosis or damage, remains to be determined.

Clinical associations of anti-endothelial cell antibodies in patients with systemic lupus erythematosus

“…Hill et al [28] reported anti-endothelial cell binding to a range of cell membrane antigens in SLE and primary anti-phospholipid syndrome, and also reported dierences in both the pattern of antibody binding and band intensity between HUVEC and HMEC-1. These results are consistent with the phenotypic variation in endothelial cells of dierent origins, and con®rm the frequent presence of autoantibodies reactive with vascular endothelium in both SLE and primary antiphospholipid syndrome.…”

No Excess of Factor V:Q506 Genotype but High Prevalence of Anticardiolipin Antibodies without Antiendothelial Cell Antibodies in Retinal Vein Occlusion in Young Patients

“…However, the ACA were not accompanied by antibodies reactive with the vascular endothelium (AECA). This situation is distinct from that in APS, where antiendothelial cell reactivity is also detectable in over 50% of cases [15, 16]. The relationship between antibodies reactive with negatively charged phospholipids and thrombosis has been established.…”

“…Anticardiolipin antibody (ACA), an APA, has been reported to be present in increased titre in the serum of 5–9% of patients with retinal vascular occlusions, both arterial and venous [10, 11, 12, 13, 14]. In primary and secondary (associated with another auto-immune disease) APS, antibody reactivity with vascular endothelial cell membrane (antiendothelial cell antibody, AECA) is also a frequent finding and may contribute to the pathogenesis [15, 16]. …”

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

“…True AECA directed against constitutive endothelial antigens and distinct from anti-␤ 2 GPI antibodies have also been found in the sera of patients with both APS and SLE-associated APS (40,44).…”

“…A recent analysis of AECA specificity in primary APS and SLE revealed differences in both the pattern of antibody binding and band intensity between membrane antigens on HUVEC and those on human microvascular EC (44). In fact, of 17 primary APS sera, antibody binding to HUVEC membranes was found in 9 sera and to human microvascular EC membranes in 7 sera.…”