Antiphospholipid antibodies are directed against epitopes of oxidized phospholipids: Recognition of cardiolipin by monoclonal antibodies to epitopes of oxidized low density lipoprotein

Journal of Clinical Investigation

Volumn 98, Issue 3, 1996, Pages 815-825

  Hörkkö, Sohvi ^a   Miller, Elizabeth ^a   Dudl, Eric ^a   Reaven, Peter ^a   Curtiss, Linda K ^b   Zvaifler, Nathan J ^a   Terkeltaub, Robert ^a   Pierangeli, Silvia S ^c   Branch, D Ware ^d   Palinski, Wulf ^a   Witztum, Joseph L ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b SCRIPPS RESEARCH INSTITUTE   (United States)

^c University of Louisville School of Medicine   (United States)

^d UNIVERSITY OF UTAH HEALTH SCIENCES CENTER   (United States)

Author keywords

antiphospholipid antibody syndrome; atherosclerosis; autoantibodies; cardiolipin; oxidized lipoproteins

Indexed keywords

CARDIOLIPIN; EPITOPE; LOW DENSITY LIPOPROTEIN; MONOCLONAL ANTIBODY; PHOSPHOLIPID; PHOSPHOLIPID ANTIBODY; UNSATURATED FATTY ACID;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIBODY TITER; ANTIPHOSPHOLIPID SYNDROME; ARTICLE; ATHEROSCLEROSIS; AUTOIMMUNITY; CLINICAL ARTICLE; CONTROLLED STUDY; FEMALE; HUMAN; HYPERLIPOPROTEINEMIA TYPE 3; LIPID OXIDATION; MOUSE; NONHUMAN; PATHOPHYSIOLOGY; PRIORITY JOURNAL;

EID: 0038871839     PISSN: 00219738     EISSN: None     Source Type: Journal    
DOI: 10.1172/JCI118854     Document Type: Article

References (71)

1. Alarcon-Segovia, D., M. Deleze, C. Oria, J. Sanchez-Guerrero, L. Gomez-Pancheco, J. Cabiedes, L. Fernandez, and S. Ponce de Leon. 1989. Antiphospholipid antibodies and the antiphospholipid syndrome in systemic lupus erythematosus. A prospective study of 500 consecutive cases. Medicine (Baltimore). 58:353-363.
2. Asherson, R.A., M.A. Khamashta, J. Ordi-Ros, R.H.W.M. Derksen, S.J. Machin, J. Barquinero, H.H. Out, E.N. Harris, M. Vilardell-Torres, and G.R.V. Hughes. 1989. The "primary" antiphospholipid syndrome: major clinical and serological features. Medicine (Baltimore). 68:366-374.
3. Harris, E.N., and S.S. Pierangeli. 1994. Antiphospholipid antibodies and the antiphospholipid syndrome. Springer Semin. Immunopathol. 16:223-245.
4. Silver, R.M., M.L. Draper, J.R. Scott, J.L. Lyon, J. Reading, and D.W. Branch. 1994. Clinical consequences of antiphospholipid antibodies: a historic cohort study. Obstet. Gynecol. 83:372-377.
5. Lockshin, M.D. 1995. Thrombosis in the antiphospholipid-antibody syndrome. N. Engl. J. Med. 333:667.
6. Vaarala, O., M. Mänttäri, V. Manninen, L. Tenkanen, M. Puurunen, K. Aho, and T. Palosuo. 1995. Anti-cardiolipin antibodies and risk of myocardial infarction in a prospective cohort of middle-aged men. Circulation. 91:23-27.
7. Peaceman, A.M., R.F. Silver, S.N. Mac Gregor, and M.L. Socol. 1992. Inter-laboratory variation in antiphospholipid antibody testing. Am. J. Obstet. Gynecol. 166:1780-1787.
8. Witztum, J.L., U.P. Steinbrecher, M. Fisher, and Y.A. Kesäniemi. 1983. Nonenzymatic glucosylation of homologous LDL and albumin render them immunogenic in the guinea pig. Proc. Natl. Acad. Sci. USA. 80:2757-2761.
9. Steinbrecher, U.P., M. Fisher, J.L. Witztum, and L.K. Curtiss. 1984. Immunogenicity of homologous low density lipoprotein after methylation, ethylation, acetylation, or carbamylation: generation of antibodies specific for derivatized lysine. J. Lipid Res. 25:1109-1116.
10. Steinberg, D., S. Parthasarathy, T.E. Carew, J.C. Khoo, and J.L. Witztum. 1989. Beyond cholesterol. Modifications of low density lipoprotein that increase its atherogenicity. N. Engl. J. Med. 320:915-924.
11. Witztum, J.L., and D. Steinberg. 1991. Role of oxidized low density lipoprotein in atherogenesis. J. Clin. Invest. 88:1785-1792.
12. Palinski, W., S. Ylä-Herttuala, M.E. Rosenfeld, S. Butler, S.A. Socher, S. Parthasarathy, L.K. Curtiss, and J.L. Witztum. 1990. Antisera and monoclonal antibodies specific for epitopes generated during the oxidative modification of low density lipoprotein. Arteriosclerosis. 10:325-335.
13. Palinski, W., M.E. Rosenfeld, S. Ylä-Herttuala, G.C. Gurtner, S.A. Socher, S. Butler, S. Parthasarathy, T.E. Carew, D. Steinberg, and J.L. Witztum. 1989. Low density lipoprotein undergoes oxidative modification in vivo. Proc. Natl. Acad. Sci. USA. 86:1372-1376.
14. Palinski, W., V. Ord, A.S. Plump, J.L. Breslow, D. Steinberg, and J.L. Witztum. 1994. ApoE-deficient mice are a model of lipoprotein oxidation in atherogenesis: demonstration of oxidation-specific epitopes in lesions and high titers of autoantibodies to malondialdehyde-lysine in serum. Arterioscler. Thromb. 14:605-616.
15. Haberland, M.E., D. Fong, and L. Cheng. 1988. Malondialdehyde-altered protein occurs in atheroma of Watanabe heritable hyperlipidemic rabbits. Science (Wash. DC). 241:215-218.
16. Boyd, H.C., A.M. Gown, G. Wolfbauer, and A. Chait. 1989. Direct evidence for a protein recognized by a monoclonal antibody against oxidatively modified LDL in atherosclerotic lesions from a Watanabe heritable hyperlipidemia rabbit. Am. J. Pathol. 135:815-825.
17. Holvoet, P., G. Perez, Z. Zhao, E. Brouwers, H. Bernar, and D. Collen. 1995. Malondialdehyde-modified low density lipoproteins in patients with atherosclerotic disease. J. Clin. Invest. 95:2611-2619.
18. Hammer, A., G. Kager, G. Dohr, H. Rabl, I. Ghassempur, and G. Jürgens. 1995. Generation, characterization, and histochemical application of monoclonal antibodies selectively recognizing oxidatively modified apoB-containing serum lipoproteins. Arterioscler. Thromb. Vasc. Biol. 15:704-713.
19. Houglum, K., M. Filip, J.L. Witztum, and M. Chojkie. 1990. Malondialdehyde and 4-hydroxynonenal protein adducts in plasma and liver of rats with iron overload. J. Clin. Invest. 86:1991-1998.
20. Yan, S.D., A.M. Schmid, G.M. Anderson, J. Zhang, J. Brett, Y.S. Zou, D. Pinsky, and D. Stern. 1994. Enhanced cellular oxidant stress by the interaction of advanced glycation end products with their receptors/binding proteins. J. Biol. Chem. 269:9889-9897.
21. Neale, T.J., P.P. Ojha, M. Exner, H. Poczewski, B. Rüger, J.L. Witztum. P. Davis, and D. Kerjaschki. 1994. Proteinuria in passive Heymann nephritis is associated with lipid peroxidation and formation of adducts on type IV collagen. J. Clin. Invest. 94:1577-1584.
22. Libby, P., and G.K. Hansson. 1991. Involvement of the immune system in human atherogenesis: current knowledge and unanswered questions. Lab. Invest. 64:5-15.
23. Witztum, J.L., and W. Palinski. 1996. Autoimmunity to oxidized lipoproteins. In: Immune Functions of the Vessel Wall. G.K. Hansson and P. Libby, editors. Harwood Academic Publishers. GmbH, New York. In press.
24. Martin, B.A., D.W. Branch, and G.M. Rodgers. 1992. The preparation of a partial thromboplastin reagent from bovine brain. Blood Coagul. Fibrinolysis. 3:287-294.
25. Martin, B.A., D.W. Branch, and G.M. Rodgers. 1996. Sensitivity of the activated partial thromboplastin time, the dilute Tussell's viper venom time, and the kaolin clotting time for the detection of the lupus anticoagulant: a direct comparison using plasma dilutions. Blood Coagul. Fibrinolysis. 7:31-38.
26. Branch, D.W., R.M. Silver, J.L. Blackwell, J.C. Reading, and J.R. Scott. 1992. Outcome of treated pregnancies in women with antiphospholipid syndrome: an update of the Utah experience. Obstet. Gynecol. 4:614-620.
27. Harris, E.N. 1990. The second international anti-cardiolipin standardization workshop / the Kingston anti-phospholipid antibody study (KAPS) group. Am. J. Clin. Pathol. 94:476-484.
28. Harris, E.N., S. Pierangeli, and D. Birch. 1994. Anticardiolipin Wet Workshop report. Fifth International Symposium on antiphospholipid antibodies. Am. J. Clin. Pathol. 101:616-624.
29. Palinski, W., S. Hörkkö, E. Miller, U.P. Steinbrecher, H.C. Powell, L.K. Curtiss, and J.L. Witztum. 1996. Cloning of monoclonal autoantibodies to epitopes of oxidized lipoproteins from apo E-deficent mice. Demonstration of epitopes of oxidized LDL in human plasma. J. Clin. Invest. 98:800-814.
30. Carbral, A.R., J. Cabiedes, and D. Alarcon-Segovia. 1994. Tween 20 delaches cardiolipin from ELISA plates and makes anticardiolipin antibodies undetectable regardless of the presence of beta 2-glycoprotein-I. J. Immunol. Methods. 175:107-114.
31. Reaven, P., S. Parthasarathy, B.J. Grasse, E. Miller, D. Steinberg, and J.L. Witztum. 1993. Effects of oleate-rich and linoleate-rich diets on the susceptibility of low density lipoprotein to oxidative modification in mildly hypercholesterolemic subjects. J. Clin. Invest. 91:668-676.
32. Ezaki, M., J.L. Witztum, and D. Steinberg. 1995. Lipoperoxides in LDL incubated with fibroblasts that overexpress 15-lipoxygenase. J. Lipid Res. 36: 1996-2004.
33. Levy, R.A., A.E. Gharavi, L.R. Sammaritano, L. Habina, and M.D. Lockshin. 1990. Fatty acid chain is a critical epitope for antiphospholipid antibody. J. Clin. Immunol. 10:141-145.
34. Pierangeli, S.S., E.N. Harris, A.E. Gharavi, G. Goldsmith, D.W. Branch, and W.L. Dean. 1993. Are immunoglobulins with lupus anticoagulant activity specific for phospholipids? Br. J. Haematol. 85:124-132.
35. Witztum, J.L. 1994. The oxidation hypothesis of atherosclerosis. Lancet (N. Am. Ed.). 344:793-795.
36. Berliner, J.A., M. Navab, A.M. Fogelman, J.S. Frank, L.L. Demer, P.A. Edwards, A.D. Watson, and A.J. Lusis. 1995. Atherosclerosis: basic mechanisms. Oxidation, inflammation, and genetics. Circulation. 91:2488-2496.
37. Branch, D.W., M.D. Mitchell, E. Miller, W. Palinski, and J.L. Witztum. 1994. Pre-eclampsia and serum antibodies to oxidised low-density lipoprotein. Lancet (N. Am. Ed.). 343:645-646.
38. Hubel, C.A., J.M. Roberts, R.N. Taylor, T.J. Musci, G.M. Rogers, and M.K. McLaughlin. 1989. Lipid peroxidation in pregnancy: new perspectives on pre-eclampsia. Am. J Obstet. Gynecol. 161:1025-1034.
39. Sheppard, B.L., and J. Bonnar. 1981. An ultrastructural study of uteroplacental spiral arteries in hypertensive and normotensive pregnancy and fetal growth retardation. Br. J. Obstet. Gynecol. 88:695-705.
40. Steinbrecher, U.P., S. Parthasarathy, D.S. Leake, J.L. Witztum, and D. Steinberg. 1984. Modification of low density lipoprotein by endothelial cells involves lipid peroxidation and degradation of low density lipoprotein phospholipids. Proc. Natl. Acad. Sci. USA. 81:3883-3887.
41. 2 activity in endothelial cell-induced modification of low density lipoprotein. Proc. Natl. Acad. Sci. USA. 82: 3000-3004.
42. Stremler, K.E., D.M. Stafforini, S.M. Prescott, G.A. Zimmerman, and T.M. McIntyre. 1989. An oxidized derivative of phosphatidylcholine is a substrate for the platelet-activating factor acetylhydrolase from human plasma. J. Biol. Chem. 264:5331-5334.
43. Itabe, H., E. Takeshima, H. Iwasaki, J. Kimura, Y. Yoshida, T. Imanaka, and T. Takano. 1994. A monoclonal antibody against oxidized lipoprotein recognizes foam cells in atherosclerotic lesions. Complex formation of oxidized phosphatidylcholines and polypeptides. J. Biol. Chem. 269:15274-15279.
44. Watson, A.D., M. Navab, S.Y. Hama, A. Sevanian, S.M. Prescott, D.M. Stafforini, T.M. McIntyre, B.N. Du, A.M. Fogelman, and J.A. Berliner. 1995. Effect of platelet activating factor-acetylhydrolase on the formation and action of minimally oxidized low density lipoprolein. J. Clin. Invest. 95:774-782.
45. Heery, J.M., M. Kozak, D.M. Stafforini, D.A. Jones, G.A. Zimmerman, T.M. McIntyre, and S.M. Prescott. 1995. Oxidatively modified LDL contains phospholipids with platelet-activating factor-like activity and stimulates the growth of smooth muscle cells. J. Clin. Invest. 96:2322-2330.
46. Asherson, R.A., M.A. Khamashta, A. Gil, J.-J. Vazquez, O. Chan, E. Baguley, and G.R.V. Hughes. 1989. Cerebrovascular disease and antiphospholipid antibodies in systemic lupus erythematosus, lupus-like disease, and the primary antiphospholipid syndrome. Am. J. Med. 86:391-399.
47. Love, P.E., and S.A. Santoro. 1990. Antiphospholipid antibodies: anticardiolipin and the lupus anticoagulant in systemic lupus erythematosus (SLE) and in non-SLE disorders. Prevalence and clinical significance. Ann. Intern. Med. 112:682-698.
48. Ginsburg, K.S., M.H. Liang, L. Newcomer, S.Z. Goldhaber, P.H. Schur, C.H. Hennekends, and M.J. Stampfer. 1992. Anticardiolipin antibodies and the risk for ischemic stroke and venous thrombosis. Ann. Intern. Med. 117:997-1002.
49. Khamashta, M.A., M.J. Cuadrado, F. Mujic, N.A. Taub, B.J. Hunt, and G.R.V. Hughes. 1995. The management of thrombosis in the antiphospholipid-antibody syndrome. N. Engl. J. Med. 332:993-997.
50. Hamsten, A., M. Björkholm, R. Norberg, U. De Faire, and G. Holm. 1986. Antibodies to cardiolipin in young survivors of myocardial infarction: an association with recurrent cardiovascular events. Lancet. i:113-116.
51. Morton, K.E., S.A. Krilis, D.W. Baron, T.P. Gavaghan, G.E. Daggard, J.B. Hickie, and C.N. Chesterman. 1986. Coronary artery bypass graft failure - an autoimmune phenomenon? Lancet. 11:1353-1357.
52. Klemp, P., R.C. Cooper, F.J. Strauss, E.R. Jordaan, J.Z. Przybojewski, and N. Nel. 1988. Anti-cardiolipin antibodies in ischaemic heart disease. Clin. Exp. Immunol. 74:254-257.
53. 2-glycoprotein I structure altered by interacting with an oxygen modified solid phase surface. J. Exp. Med. 179:457-462.
54. 2-glycoprotein 1 (apolipoprotein H). Proc. Natl. Acad. Sci. USA. 87:4120-4124.
55. Galli, M., P. Comfurius, C. Maassen, H.C. Hemker, M.H. de Baets, P.J. van Breda-Vriesman, T. Barbui, R.F. Zwaal, and E.M. Bevers. 1990. Anticardiolipin antibodies (ACA) directed not to cardiolipin but to a plasma protein cofactor. Lancet (N. Am. Ed.). 335:1544-1547.
56. Pierangeli, S.S., E.N. Harris, S.A. Davis, and G. DeLorenzo. 1992. Beta 2-glycoprotein I (beta 2GP1) enhances cardiolipin binding activity but is not the antigen for antiphospholipid antibodies. Br. J. Haematol. 82:565-570.
57. Gharavi, A.E., L.R. Sammaritano, J. Wen, and K.B. Elkon. 1992. Induction of antiphospholipid autoantibodies by immunization with beta 2 glycoprotein I (apolipoprotein H). J. Clin. Invest. 90:1105-1109.
58. Pierangeli, S.S., and E.N. Harris. 1993. Induction of phospholipid-binding antibodies in mice and rabbits by immunization with human beta 2 glycoprotein I or anticardiolipin antibodies alone. Clin. Exp. Immunol. 93:269-272.
59. Steinkasserer, A., C. Estaller, E.H. Weiss, R.B. Sim, and A.J. Day. 1991. Complete nucleotide and deduced amino acid sequence of human beta 2-glycoprotein I. Biochem. J. 277:387-391.
60. Vaarala, O., T. Palosuo, M. Kleemola, and K. Aho. 1986. Anticardiolipin response in acute infections. Clin. Immunol. Immunopathol. 41:8-15.
61. Vaarala, O., G. Alfthan, M. Jauhiainen, M. Leirisalo-Repo, K. Aho, and T. Palosuo. 1993. Grossreaction between antibodies to oxidized low-density lipoprotein and to cardiolipin in systemic lupus erythematosus. Lancet (N. Am. Ed.). 341:923-925.
62. Amara, A., J. Constans, C. Chaugier, A. Sebban, L. Dubourg, E. Peuchant, J.L. Pellegrin, B. Leng, C. Conri, and M. Geffard. 1995. Autoantibodies to malondialdehyde-modified epitope in connective tissue diseases and vasculitides. Clin. Exp. Immunol. 101:233-238.
63. Savolainen, A., R. von Essen, J. Leikola, G. Alfthan, O. Vaarala, T. Palosuo, and K. Aho. 1995. Antibodies against oxidised low-density lipoprotein in juvenile chronic arthritis. Scand. J. Rheumatol. 24:209-211.
64. Hashimoto, Y., M. Kawamura, K. Ichikawa, T. Suzuki, T. Sumida, S. Yoshida, E. Matsuura, S. Ikehara, and T. Koike. 1992. Anticardiolipin antibodies in NZW × BXSB F1 mice. A model of antiphospholipid syndrome. J. Immunol. 149:1063-1068.
65. Mizutani, H., Y. Kurata, S. Kosugi, M. Shiraga, H. Kashiwagi, Y. Tomiyama, Y. Kanakura, R.A. Good, and Y. Matsuzawa. 1995. Monoclonal anticardiolipin autoantibodies established from the (New Zealand White × BXSB) F1 mouse model of antiphospholipid syndrome cross-react with oxidized low-density lipoprotein. Arthritis Rheum. 38:1382-1388.
66. Mironova, M., G. Virella, and M.F. Lopes-Virella. 1996. Isolation and characterization of human antioxidized LDL autoantibodies. Arterioscler. Thromb. Vasc. Biol. 16:222-229.
67. Alving, C.R. 1986. Antibodies to liposomes, phospholipids and phosphate esters. Chem. Phys. Lipids. 40:303-314.
68. Rauch, J., and A.S. Janoff. 1990. Phospholipid in the hexagonal II phase is immunogenic: evidence for immunorecognition of nonbilayer lipid phases in vivo. Proc. Natl. Acad. Sci. USA. 87:4112-4114.
69. Swartz, G.M., Jr., M.K. Gentry, L.M. Amende, E.J. Blanchette-Mackie, and C.R. Alving. 1988. Antibodies to cholesterol. Proc. Natl. Acad. Sci. USA. 85:1902-1906.
70. Bashir, S., G. Harris, M.A. Denman, D.R. Blake, and P.G. Winyard. 1993. Oxidative DNA damage and cellular sensitivity to oxidative stress in human autoimmune diseases. Ann. Rheum. Dis. 52:659-666.
71. Frenkel, K., J. Karkoszka, E. Kim, and E. Taioli. 1993. Recognition of oxidized DNA bases by sera of patients with inflammatory diseases. Free Radical Biol. Med. 14:483-494.