Summary
A cellular enzyme-linked immunosorbent assay (ELISA) was used to detect circulating anti-endothelial cell antibodies (AECA) in sera of patients suffering from rheumatoid arthritis (RA), Felty's syndrome (FS), systemic lupus erythemtosus (SLE), progressive systemic sclerosis (PSS) and those with a “lupus anticoagulant” (LA). IgG AECA were detected in RA, FS, SLE and LA sera, while IgM AECA were only detected in RA and FS. AECA were not specific for endothelial cells. However, IgG binding to endothelial cells and dermal fibroblasts was F(ab) mediated while in all other cell types tested, nonspecific binding most likely via the Fc region occurred. In RA and FS rheumatoid factor was shown to augment immunoglobulin binding to endothelial cells. Additional studies revealed that some of these pathological sera also contained cytotoxic IgG autoantibodies which fixed complement and damaged human umbilical vein endothelial cells in vitro. These studies suggest that a group of autoantibodies, present in a variety of collagen vascular disorders, react with endothelial cells and thus may be important aetiopathogenic factors in the vasculopathies associated with these disorders.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Scott DGI, Bacon PA (1983) Rheumatoid vasculitis. Clin Rheumatol 2: 311–315
Cines DB, Lyss AP, Reeber M, Bina M, DeHoratius RJ (1984) Presence of complement-fixing anti-endothelial cell antibodies in systemic lupus erythematosus. J Clin Invest 73: 611–625
Kahaleh MB, Sherer GK, Leory EC (1979) Endothelial injury in scleroderma. J Exp Med 149: 1326–1335
Kahaleh MB, Leroy EL (1983) Endothelial injury in scleroderma. A protease mechanism. J Lab Clin Med 101: 533–560
Cohen S, Johnson AR, Hurd E (1983) Cytotoxicity of sera from patients with scleroderma — effects on human endothelial cells and fibroblasts in culture. Arthritis Rheum 26: 170–175
Drenk F, Mensing H, Serbin A, Deicher H (1985) Studies on endothelial cell cytotoxic activity in sera of patients with progressive systemic sclerosis. Raynaud syndrome, rheumtoid arthritis and systemic lupus erythematosus. Rheumatol Int 5: 259–263
Drenk KF, Deicher HRG (1988) Pathophysiological effects of endothelial cytotoxic activity derived from sera of patients with progressive systemic sclerosis. J Rheumatol 15: 468–474
Penning CA, French MAH, Rowell NR, Hughes P (1985) Antibody-dependent cellular cytotoxicity of human vascular endothelium in systemic lupus erythematosus. J Clin Lab Immunol 17: 125–129
Kelsey PR, Stevenson KJ, Poller L (1984) The diagnosis of lupus anticoagulants by the activated thromboplastin time. The central role of phosphatidyl serine. Thromb Haemost 52: 172–175
Boey ML, Colaco CB, Gharavi AE, Elkon KB, Loizou S, Hughes GRV (1983) Thrombosis in systemic lupus erythematosus: striking association with the presence of circulating lupus anticoagulant. Br Med J 287: 1021–1023
Lubbe WF, Butler WS, Liggins GC (1984) The lupus anticoagulant: clincial and obstetric implications. NZ Med J 97: 398–402
Carreras LO, Defreyh G, Machin SJ, Vermylen J, Deman R, Spitz B, Van Assche A (1981) Arterial thrombosis intra uterine death and “lupus” anticoagulant: detection of immunoglobulin interfering with prostacyclin formation. Lancet I: 244–246
Angles-Cano E, Sultan Y, Clauvel J (1979) Predisposing factors to thrombosis in systemic lupus erythematosus. Possible relation to endothelial cell damage. J Lab Clin Med 94: 312–323
Cariou R, Tobelem G, Soria C, Caen J (1986) Inhibition of protein C activation by endothelial cells in the presence of lupus anticoagulant. N Engl J Med 314: 1193–1194
LeRoux G, Wautier M-P, Guillevin L, Wautier J-L (1986) IgG binding to endothelial cells in systemic lupus erythematosus. Thromb Haemost 56: 144–146
Jaffe EA, Nachman RL, Becker CG, Minick CR (1973) Culture of human endothelial cells derived from umbilical veins. Indentification by morphologic and immunologic criteria. J Clin Invest 52: 2745–2756
Gimbrone MA, Cotran RS, Folkman J (1974) Human vascular endothelial cells in culture. Growth and DNA synthesis. J Cell Biol 60: 673–684
Avrameas S, Ternynck T (1969) The cross linking of proteins with glutaraldehyde and its use in preparations of immunoadsorbents. Immunochem 6: 53–60
Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principal of protein-dye binding. Anal Biochem 72: 248–254
Tan EM, Pearson CM (1972) Rheumatic disease sera reactive with capillaries in the mouse kidney. Arthritis Rheum 15: 23–28
Shingu M, Hurd ER (1981) Sera from patients with systemic lupus erythematosus reactive with human endothelial cells. J Rheumatol 8: 581–586
Hashemi S, Smith CD, Izaguirre LA (1987) Anti-endothelial cell antibodies: detection and characterisation using a cellular enzyme-linked immunosorbent assay. J Lab Clin Med 109: 434–440
Rosenbaum J, Pottinger BE, Woo P, Black CM, Loizou S, Byron MA, Pearson JD (1988) Measurement and characterisation of circulating anti-endothelial cell IgG in connective tissue diseases. Clin Exp Immunol 72: 450–456
Andrews BS, Shadforth M, Cunningham P, Davis JS (1981) Demonstration of a C1q receptor on the surface of human endothelial cells. J Immunol 127: 1075–1080
Ryan US (1986) The endothelial surface and response to injury. Fed Proc 45: 101–108
Bacon PA (1985) Evolving concepts in vasculitis. Q J Med 222: 609–610
Scott DGI, Blake DR, Blann A, Salmon M, Brailsford S, Winyard P, Bacon PA (1984) The role of lymphocytes and serum factors in vasculitis diseases. Ann Rheum Dis (abstract) 43: 116
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Quadros, N.P., Roberts-Thomson, P.J. & Gallus, A.S. IgG and IgM anti-endothelial cell antibodies in patients with collagen-vascular disorders. Rheumatol Int 10, 113–119 (1990). https://doi.org/10.1007/BF02274825
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02274825