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DOI: 10.1055/s-0038-1649940
Induction of Thrombosis in a Mouse Model by IgG, IgM and IgA Immunoglobulins from Patients with the Antiphospholipid Syndrome
Publication History
Received 17 May 1995
Accepted after revision14 July 1995
Publication Date:
10 July 2018 (online)
Summary
Antiphospholipid syndrome is a disorder of recurrent thrombosis and pregnancy losses associated with production of anticardiolipin antibodies and lupus anticoagulant positivity. Recently, we have adapted a mouse model of induced venous thrombosis to study the role of autoantibodies in thrombus formation. To determine whether immunoglobulins from patients with the antiphospholipid syndrome play a role in thrombosis, we injected groups of CDI mice either with immunoglobulins purified from seven patients with the antiphospholipid syndrome (nine preparations studied: four IgG, three IgM and two IgA) or with immunoglobulins of the same isotype from healthy controls. Seventy- two h after injection, a non-occlusive thrombus was induced in the femoral veins of experimental mice by a pinch injury; the thrombus areas as well as times of formation and disappearance of the thrombi were measured. Eight of the nine antiphospholipid syndrome immunoglobulin preparations caused a significant increase in mean thrombus area and a significant delay in mean thrombus disappearance time as compared with normal controls. To determine whether anticardiolipin antibodies might be involved, separate groups of mice were injected with affinity-purified IgG (n = 2) or IgM (n = 2) anticardiolipin antibodies or with normal immunoglobulins of the same isotype, and the effects on thrombus formation compared. Mean thrombus area and mean disappearance times were again significantly increased in all four groups injected with affinity-purified antibodies. This is the first study to show that anticardiolipin antibodies of IgG, IgM and IgA isotypes may play a role in thrombosis in vivo.
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References
- 1 Harris EN, Gharavi AE, Hughes GRV. Anti-phospholipid antibodies. Clin Rheum Dis 1985; 11: 591-609
- 2 Derksen RHW M, Kater L. Lupus anticoagulant: revival of an old phenomenon. Clin Exp Rheumatol 1985; 3: 349-357
- 3 Love PE, Santoro SA. Antiphospholipid antibodies: anticardiolipin and the lupus anticoagulant in systemic lupus erythematosus (SLE) and in non-SLE disorders: prevalence and clinical significance. Ann Int Med 1990; 12: 682-698
- 4 Sammaritano LR, Gharavi AE, Lockshin MD. Antiphospholipid antibody syndrome: immunologic and clinical aspects. Semin Arth Rheum 1990; 20: 81-96
- 5 McNeil HP, Chesterman CN, Krilis SA. Immunology and clinical importance of antiphospholipid antibodies. Adv Immunol 1991; 49: 193-280
- 6 Harris EN, Chan JK H, Asherson RA, Aber VR, Gharavi AE, Hughes GRV. Thrombosis, recurrent fetal loss and thrombocytopenia. Predictive value of the anti-cardiolipin antibody test Arch Intern Med 1986; 146: 2153-2156
- 7 Ginsburg KS, Liang MH, Newcomer L, Goldhaber SZ, Schur PH, Hennekens CH, Stampler MJ. Anticardiolipin antibodies and the risk for ischemic stroke and venous thrombosis. Ann Intern Med 1992; 117: 997-1002
- 8 Alving BM, Barr CF, Tank DB. Correlation between lupus anticoagulants and anticardiolipin antibodies in patients with prolonged activated partial thromboplastin times. Am J Med 1990; 88: 112-116
- 9 Lockshin MD, Druzin ML, Qamar T. Prednisone does not prevent recurrent fetal death in women with antiphospholipid antibody. Am J Obstet Gynecol 1989; 160: 439-443
- 10 Loizou S, Byron MA, Englert HR, Walport MJ, Hughes GR V. Association of quantitative anti-cardiolipin antibody levels with fetal loss. Quart J Med 1988; 68: 525-531
- 11 Shapiro SS, Thiagarajan P. Lupus anticoagulant. Progress in Haemostas Thromb 1982; 6: 263-285
- 12 Triplett DA. Antiphospholipid antibodies and thrombosis. A consequence, coincidence, or cause? Arch Pathol Lab Med 1993; 117: 78-88
- 13 Alving BM. Lupus anticoagulants, anticardiolipin antibodies and the APS. In: Thrombosis and Hemorrhage. Loscalzo J, Schafer A. eds Blackwell Scientific Publications; Boston, MA: 1994. pp 749-765
- 14 Harris EN. Antiphospholipid Antibodies and Cardiovascular Disease. In: Atherosclerotic cardiovascular disease, hemostasis, and endothelial function. Francis RB. ed Marcel Dekker, Inc.,; NY, NY: 1992. pp 237-276
- 15 Branch DW, Dudley DJ, Mitchell MD. Immunoglobulin G fractions from patients with antiphospholipid antibodies cause fetal death in BABL/c mice: A model for autoimmune fetal loss. Am J Obstet Gynecol 1990; 163: 120
- 16 Blank M, Cohen J, Toder V, Shoenfeld Y. Induction of antiphospholipid syndrome in naive mice with mouse lupus monoclonal and human polyclonal anticardiolipin antibodies. Proc Natl Acad Sci 1991; 88: 3069-3073
- 17 Bakimer R, Fishman P, Blank M, Srednc B, Djaidetti M, Shoenfeld Y. Induction of primary antiphospholipid syndrome in mice by immunization with a human monoclonal anticardiolipin antibody (H-3). J Clin Invest 1992; 89: 1558-1563
- 18 Sthoeger ZM, Mozes E, Tartakovsky B. Anti-cardiolipin antibodies induce pregnancy failure by impairing embryonic implantation. Proc Natl Acad Sci (USA) 1993; 90: 6464-6467
- 19 Blank M, Tincani A, Shoenfeld Y. Induction of experimental antiphospholipid syndrome in naive mice with purified IgG antiphosphatidylserine antibodies. J Rheumatol 1994; 21: 100-104
- 20 Pierangeli SS, Barker JH, Stikovac D, Anderson G, Ackerman D, Barquinero J, Acland R, Harris EN. Effect of human IgG antiphospholipid antibodies on an in vivo thrombosis model in mice. Thromb Haemost 1994; 71: 670-674
- 21 Harris EN. Syndrome of the Black Swan. Br J Rheumatol 1987; 26: 324-326
- 22 Weir DM. Handbook of Experimental Immunology (Vol 1). Blackwell Scientific Publishers; 1973
- 23 Harris EN, Gharavi AE, Tincani A, Chan JK H, Englert H, Mantelli P, Allegro F, Balestrieri G, Hughes GR V. Affinity-purified anti-cardiolipin and anti-DNA antibodies. J Clin Lab Immunol 1986; 16: 1-6
- 24 Pierangeli SS, Goldsmith GH, Kmic S, Harris EN. Differences in functional activity of anticardiolipin antibodies from patients with syphilis and the antiphospholipid syndrome. Infect Immun 1994; 62 (09) 4081-4084
- 25 Harris EN. Annotation. Antiphospholipid Antibodies Br J Haematol 1990; 74: 1-9
- 26 Gharavi AE, Harris EN, Asherson RA, Hughes GR V. Anticardiolipin antibody isotype distribution and phospholipid specificity. Ann Rheum Dis 1987; 46: 41-46
- 27 Harris EN, Pierangeli SS, Birch D. Anticardiolipin wet workshop report: Vth International Symposium on Antiphospholipid Antibodies. Am J Clin Pathol 1994; 101 (05) 616-624
- 28 Asherson RA. The catastrophic antiphospholipid syndrome. J Rheumatol 1992; 19: 508-512
- 29 Harris EN, Bos K. An acute disseminated coagulopathy-vasculopathy associated with the Antiphospholipid Syndrome. Arch Intern Med 1991; 151: 231-233
- 30 Greisman CG, Thayamparan RS, Goodwin TA, Lockshin MD. Occlusive vasculopathy in systemic lupus erythematosus: association with anticardiolipin antibody. Arch Intern Med 1991; 151: 389-392
- 31 Arvieux J, Pouzol P, Roussel B, Jacab MC, Colomb MG. Measurement of antiphospholipid antibodies by ELISA using β2glycoprotein 1 as an antigen. Br J Haematol 81: 568-573
- 32 Galli M, Comfurius P, Maasen C, Heinker HC, deBaets MH, Van-Breda Vriesman PJ C, Barbui T, Zwaal RF A, Bevers EM. Anticardiolipin antibodies (ACA) directed not to cardiolipin but to a plasma protein cofactor. Lancet 1990; 336: 544-547
- 33 Matsuura E, Igarashi Y, Yasuda T, Triplett DA, Koike T. Anticardiolipin antibodies recognize β2glycoprotein 1 structure altered by interacting with an oxygen modified solid phase surface. J Exp Med 1994; 179: 457-462
- 34 Roubey RA S. Autoantibodies to phospholipid-binding plasma proteins, a new view of lupus anticoagulant and other “antiphospholipid” autoantibodies. Blood 1994; 84: 2854-2867
- 35 Permpikul P, Rao LV M, Rapaport SI. Functional and binding studies of the role of prothrombin and β2glycoprotein 1 in the expression of lupus anticoagulant activity. Blood 1994; 83: 2878-2892
- 36 Oosting JD, Derksen RHW M, Bobbink IW G, Hackeng TM, Bouma BN, de Groot PG. Antiphospholipid antibodies directed against a combination of phospholipids with prothrombin, protein C, or protein S: an explanation for their pathogenic mechanism. Blood 1993; 81: 2618-2625
- 37 Vermylen J, Amout J. Is the antiphospholipid syndrome caused by antibodies directed against physiologically relevant phospholipid-protein complexes. J Lab Clin Med 1992; 120: 10-11
- 38 Lechner K, Pabinger-Fasching I. Lupus anticoagulant and thrombosis. A study of 25 cases and review of the literature Haemost 1985; 15: 254-262
- 39 Weidman CE, Wallace DJ, Peter JB. Studies of IgG, IgM and IgA antiphospholipid isotypes in systemic lupus erythematosus. J Rheumatol 1988; 15: 74-79
- 40 Asherson RA, Mackworth-Young CG, Harris EN, Gharavi AE, Hughes GR V. Multiple venous and arterial thrombosis associated with the lupus anticoagulant and antibodies to cardiolipin in the absence of SLE. Rheumatol Int 1985; 5: 91-93
- 41 Kalunian KC, Peter JC, Middlekauff HR, Sayre J, Ando DG, Mangotich M, Hahn BH. Clinical significance of a single test for anti-cardiolipin antibodies in patients with systemic lupus erythematosus. Am J Med 1988; 85: 602-608
- 42 Vaarala O, Palosuo T, Kleemola M, Aho K. Anticardiolipin response in acute infections. Clin Immunol Immunopathol 1986; 41: 8-15
- 43 Zarrabi MH, Zucker S, Miller F, Derman RM. Immunologic and coagulation disorders in chlorpromazine-treated patients. Ann Intern Med 1979; 91: 195-199
- 44 Canoso RT, Zon LI, Groopman JE. Anticardiolipin antibodies associated with HTLV-III infection. Br J Haematol 1987; 65: 495-499
- 45 Gharavi AE. Anti-phospholipid syndrome in murine lupus. In: Phospholipid Binding Antibodies. Harris EN, Exner T, Asherson RA. eds CRC Press; Boca Raton, FL: 1991. pp 403-416
- 46 Smith HR, Hansen CL, Rose R, Canoso RT. Autoimmune MRL-1 pr/lpr mice are an animal model for the secondary antiphospholipid syndrome. J Rheumatol 1990; 17: 911-915
- 47 Carreras LO, Vermylen JG. ‘Lupus’ anticoagulant and thrombosis - possible role of inhibition of prostacyclin formation. Thromb Haemost 1982; 48: 28-40
- 48 Branch DW, Rodgers GM. Induction of endothelial cell tissue factor activity by sera from patients with antiphospholipid syndrome: A possible mechanism for thrombosis. Am J Obstet Gynecol 1993; 168: 206-210
- 49 Martinuzzo MB, Maclouf J, Carreras LO, Levy-Toledano S. Antiphospholipid antibodies enhance throinbin-indueed platelet activation and thromboxane formation. Thromb Haemost 1993; 70: 667-671
- 50 Campbell AL, Pierangeli SS, Wellhausen S, Harris EN. Autoimmune antiphospholipid antibodies enhance activation and aggregation of human platelets in vitro. Thromb Haemost 1995; 73: 529-534
- 51 Cariou R, Tobelin G, Bellucci S, Soria J, Soria C, Maclouf j, Caen J. Effect of the lupus anticoagulant on antithrombogenie properties of endothelial cells inhibition of thrombomodulin dependent protein C activation. Thromb Haemost 1985; 60: 54-58
- 52 Marciniak E, Romond ED. Impaired catalytic function of activated protein C: A new in vitro manifestation of lupus anticoagulant. Blood 1989; 74: 2426-2432
- 53 Malia RG, Kitchen S, Greaves M, Preston FE. Inhibition of activated protein C anil its cofactor protein S by antiphospholipid antibodies. Br J Haematol 1990; 76: 101-107