Summary
We conducted an investigation to clarify whether or not the levels of total, free, and functional protein S and C4-binding protein (C4bp) in plasma are decreased in systemic lupus erythematosus (SLE) patients, especially those with antiphospholipid antibody (aPL), which is known to be a causative factor of such complications as habitual abortion and arteriovenous thrombosis. Fifty patients with SLE were recruited as subjects of the study. Serum aPL (anticardiolipin, antiphosphatidyl serine, antiphosphatidyl inositol, and antiphosphatidic acid antibodies) were measured by ELISA. Lupus anticoagulant was determined by aPTT, KCT, and diluted RVVT. Furthermore, plasma concentrations of total, free, and functional protein S and C4bp were measured. There were no significant differences in the mean levels of total, free, or functional protein S and C4bp between aPL-positive, aPL-negative SLE patients, and the healthy controls. From these results, we concluded that the protein S level is not the sole factor causing complications, and that other factor(s) may be involved in the induction of such complications in this clinical setting.
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References
Triplett DA (1993) Antiphospholipid antibodies and thrombosis. Consequence, coincidence, or cause? Arch Pathol Lab Med 117:78–88
McNeil HP, Krilis SA (1992) Antiphospholipid antibodies. Aust NZ J Med 21:463–475
McNeil HP, Simpson RJ, Chesterman CN, Krilis S (1990) Antiphospholipid antibodies are directed against a complex antigen that includes a lipid-binding inhibitor of coagulation: β2- glycoprotein I (apolipoprotein H). Proc Natl Acad Sci USA 87:4120–4124
Galli M, Comfurius P, Maasen C, Hemker HC, De Baets MH, van Breda-Vrisman PJC, Zwall RFA, Bevers EM (1990) Anticardiolipin antibodies directed not to cardiolipin but to a plasma protein cofactor. Lancet 335:1544–1551
Matsuda J, Saitoh N, Gohchi K, Gotoh M, Tsukamoto M (1994) Detection of beta-2-glycoprotein-I-dependent antiphospholipid antibodies and anti-beta-2-glycoprotein-I antibody in patients with systemic lupus erythematosus and in patients with syphilis. Int Arch Allergy Immunol 103:239–244
Schousboe I (1985) A plasma inhibitor of the intrinsic blood coagulation pathway. Blood 66:1086–1091
Nimpf J, Wurm H, Kostner MC (1987) β2-glycoprotein I (apo-H) inhibits the release reaction of human platelets during ADP-induced aggregation. Atheroscl 63:109–114
Galli M, Bevers EM, Comfurius P, Barbui T, Zwaal FA (1992) Anticoagulant activity of anticardiolipin antibodies is mediated by β2-glycoprotein I. Thromb Haemost 68:297–300
Rossi E, Gatti L, Guarneri D (1992) Functional protein S in women with lupus anticoagulant inhibitor. Thromb Res 65:253–262
Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, Shaller JG, Talal N. Winshester RJ (1982) Revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 25:1271–1277
Exner T, Triplett DA, Taberner D, Machin SJ (1991) Guidelines for testing and revised criteria for lupus anticoagulants. SS subcommitee for the standardization of lupus anticoagulants. Thromb Haemost 65:320–325
Matsuura E, Igarashi Y, Fujimoto M, Ichikawa K, Suzuki T, Sumida T, Yasuda T, Koike T (1992) Heterogeneity of anticardiolipin antibodies defined by the anticardiolipin cofactor. J Immunol 148:3885–3891
Malia RG, Kitchen S, Greaves M, Preston FE (1990) Inhibition of activated protein C and its cofactor protein S by antiphospholipid antibodies. Br J Haematol 76:101–107
Parke A, Weinstein RE, Bona RD, Maier D (1992) The thrombotic diathesis associated with the presence of phospholipid antibodies may be due to low levels of free protein S. Am J Med 93:49–54
Kordich LC, Forastiero RR, Basilotta E, Porterie P, Carreras LO (1992) Natural inhibitors of blood coagulation and fibrinolysis in patients with lupus anticoagulant. Blood Coagul Fibrinolysis 3:765–771
Taylor FB jr (1992) Protein S, C4b binding protein, and the hypercoagulable state. J Lab Clin Med 119:596–597
Lo SC, Salem HH, Howard MA, Oldmeadow MJ, Firkin BG (1990) Studies of natural anticoagulant protein and anticardiolipin antibodies in patients with lupus anticoagulant. Br J Haematol 76:380–386
Tsakiris DA, Settas L, Makris PE, Marbet GA (1990) Lupus anticoagulant, antiphospholipid antibodies and thrombophilia. Relation to protein C, protein S, thrombomodulin. J Rheumatol 65:62H-66H
Koster T, Rosendaal FR, de Ronde H, Briët E, Vandenbroucke JP, Bertina RM (1993) Venous thrombosis due to poor anticoagulant response to activated protein C: Leiden thrombophilia study. Lancet 342:1503–1506
Dahlbäck B (1991) Protein S and C4b-binding protein: components involved in the regulation of the protein C anticoagulant system. Thromb Haemost 66:49–61
Nukatsuka M, Nagasawa S (1987) Characterization of the interaction between human protein S and C4b-binding protein (C4bp). J Biochem (Tokyo) 102:599–605
Walker FJ (1993) Does beta-2-glycoprotein I inhibit the interaction between protein S and C4b-binding protein? Proc. XIV Congress Intl. Society of Thrombosis and Haemostasis 1993, p 930 (Abstr no 1406)
Comp PC, Forristall J, West CD, Trapp RG (1990) Free protein S levels are elevated in familial C4bp-binding protein deficiency. Blood 76:2527–2529
Ruiz-Argüelles GJ, Ruiz-Argüelles A, Pérez-Romano B, Alarcón-Segovia D (1993) Protein S deficiency associated to antiprotein S antibodies in a patient with mixed connective-tissue disease and its reversal by danazol. Acta Haematol 89:206–208
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Matsuda, J., Gohchi, K., Gotoh, M. et al. Plasma concentrations of total/free and functional protein S are not decreased in systemic lupus erythematosus patients with lupus anticoagulant and/or antiphospholipid antibodies. Ann Hematol 69, 311–315 (1994). https://doi.org/10.1007/BF01696561
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DOI: https://doi.org/10.1007/BF01696561