During the last few years several murine models for APS have been described. These include spontaneous occurring disease, or APS induced by immunization with pathogenic autoantibodies. Employing those models, several treatment modalities, in different stages of the disease, were studied. Treatments which showed promising potential for application in patients with APS include immunomodulation with specific anti-idiotypic or anti-CD4 antibodies, treatment with IL-3, high-dose intravenous immunoglobulins, ciprofloxacin or bromocriptine, as well as antithrombotic and anticoagulant treatments using aspirin and/or low-molecular-weight heparin. Bone-marrow transplantation was also found to improve clinical and serological manfestations of the disease. These studies might promote the handling of controlled clinical trials assessing their efficacy in APS patients.
SmithHRHansenCLRoseRCanosoRT. Autoimmune MRL/lpr/lpr mice are an animal model for the secondary antiphospholipid syndrome. J Rheumatol1990; 17: 911–915
3.
HashimotoYAnticardiolipin antibodies in NZW×B×SB F1 mice: a model of antiphospholipid syndrome. J Immunol1992; 149: 1063–1069
4.
BakimerRInduction of primary anti-phospholipid syndrome in mice by immunization with human monoclonal anti-cardiolipin antibody (H-3). J Clin Invest1992; 89: 1558–1563
5.
BlankMImmunization with anti-neutrophil cytoplasmic antibody (ANCA) induces the production of mouse ANCA and perivascular lymphocyte infiltration. Clin Exp Immunol1995; 102: 120–130
6.
ShoenfeldY.Idiotypic induction of autoimmunity: a new aspect of the idiotypic network. FASEB J1994; 8: 1296–1301
7.
MendlovicSThe genetic regulation of the induction of experimental SLE. Immunology1990; 69: 228–236
8.
YodfatOBlankMKrauseIShoenfeldY. The pathogenic role of anti-phosphatidylserine antibodies: active immunization with the antibodies leads to the induction of antiphospholipid syndrome. Clin Exp Immunol1996; 78: 14–20
9.
BlankMKrauseIBen-BassatMShoenfeldY. Induction of experimental anti-phospholipid syndrome associated with SLE following immunization with human monoclonal pathogenic anti-DNA idiotype. J Autoimmunity1992; 5: 495–509
10.
GharaviAESammaritanoLRWenJElkonKB. Induction of antiphospholipid antibodies by immunization with β2-glycoprotein I (apolipoprotein H). J Clin Invest1992; 90: 1105–1109
11.
BlankMImmunization with anticardiolipin cofactor (β2-glycoprotein I) induces experimental anti-phospholipid syndrome in naive mice. J Autoimmun1994; 7: 441–455
12.
BlankMCohenJToderVShoenfeldY. Induction of antiphospholipid syndrome in naive mice with mouse lupus monoclonal and human polyclonal anticardiolipin antibodies. Proc Natl Acad Sci USA1991; 88: 3069–3073
13.
BranchDWImmunoglobulin G fractions from patients with antiphospholipid antibodies causes fetal death in Balb/c mice: a model for autoimmune fetal loss. Am J Obstet Gynecol1990; 163: 210–216
14.
BranchDWScottJRKochenourNKHershgoldE. Obstetric complications associated with the lupus anticoagulants. N Engl J Med1985; 313: 1322–1326
15.
FitzgeraldGAEndogenous biosynthesis of prostacycline and thromboxane and platelet function during chronic administration of aspirin in man. J Clin Invest1983; 71: 676–688
16.
SilveraLHPrevention of anticardiolipin antibody-related pregnancy losses with prednisone and aspirin. Am J Med1992; 93: 403–411
17.
KrauseIBlankMGilbrutBShoenfeldY. The effect of aspirin on recurrent fetal loss in experimental antiphospholipid syndrome. Am J Reprod Immunol1993; 29: 155–161
18.
ShoenfeldYBlankM. Effect of long-acting thromboxane receptor antagonist (BMS 180,291) on experimental antiphospholipid syndrome. Lupus1994; 3: 397–400
19.
RosoveMHHeparin therapy for pregnant women with lupus anticoagulant or anticardiolipin antibodies. Obstet Gynecol1990; 75: 630–634
20.
InbarOPrevention of fetal loss in experimental antiphospholipid syndrome by low-molecular-weight heparin. Am J Obstet Gynecol1993; 169: 423–426
21.
NIH. Consensus Conference. Intravenous immunoglobulin prevention and treatment of disease. JAMA1990; 264: 3189–3193
22.
DweyerJM. Manipulating the immune system with immune globulin. N Engl J Med1992; 326: 107–116
23.
BakimerRGilbrudBZurgilNShoenfeldY. The effect of intravenous-globulin on the induction of experimental anti-phospholipid syndrome. Clin Immunol Immunopathol1993; 69: 97–102
24.
KrauseIAbrogation of experimental systemic lupus erythematosus and primary antiphospholipid syndrome with intravenous gamma globulin. J Rheumatol1995; 6: 1068–1074
25.
WegmannTG. The cytokine basis for cross talk between the maternal immune and reproductive system. Curr Opin Immunol1990; 2: 765–769
26.
FishmanPPrevention of fetal loss in experimental antiphospholipid syndrome by in vivo administration of recombinant interleukin-3. J Clin Invest1993; 91: 1834–1837
27.
FishmanPAspirin-Interleukin-3 interrelationships in patients with anti-phospholipid syndrome. Am J Reprod Immunol1995; 35: 80–84
28.
FishmanPAspirin modulates Interleukin-3 production: additional explanation for the preventive effects of aspirin in antiphospholipid antibody syndrome. J Rheumatol1995; 22: 1086–1090
29.
BuskilaDSukenicSShoenfeldY. The possible role of prolactin in autoimmunity. Am J Reprod Immunol1991; 26: 118–123
30.
BlankMBromocriptine immunomodulation of experimental SLE and primary anti-phospholipid syndrome via induction of nonspecific T suppressor cells. Cell Immunol1995; 162: 114–122
31.
ZanettiM. The idiotype network in autoimmunoprocesses. Immunol Today1995; 6: 299–302
32.
AguisMARichmannDP. Suppression of development of experimental autoimmune myasthenia gravis with isogenic monoclonal anti idiotypic antibody. J Immunol1986; 137: 2195–2198
33.
ZouSRWhitakerJN. Specific modulation of T cells and murine experimental allergic encephalomyelitis by monoclonal anti-idiotypic antibodies. J Immunol1993; 150: 1629–1642
34.
BlankMSuppression of experimental systemic lupus erythematosus (SLE) with specific anti-idiotypic antibody-saporin conjugate. Clin Exp Immunol1994; 98: 434–441
35.
KoingRHuangLYGermainRN. MHC class II interaction with CD4 mediated by a region analogous to the MHC class I binding site for CD8. Nature1992; 356: 796–798
36.
BenjaminRJWaldmannH. Induction of tolerance by monoclonal antibody therapy. Nature1986; 320: 449–451
37.
ShizuruJAImmunotherapy of the nonobese diabetic mouse; treatment with an antibody to T-helper lymphocytes. Science1988; 240: 659–662
38.
WaldorMKReversal of experimental allergic encephalomyelitis with monoclonal antibody to a T-cell subset marker. Science1985; 227: 415–417
39.
TomerYBlankMShoenfeldY. Suppression of experimental antiphospholipid syndrome and systemic lupus erythematosus in mice by anti-CD4 monoclonal antibodies. Arthritis Rheum1994; 37: 1236–1244
40.
KraussisDMPrevention of experimental autoimmune encephalomyelitis and induction of tolerance with acute immunosuppression followed by syngeneic bone marrow transplantation. J Immunol1993; 148: 1693–1698
41.
IkeharaSPrevention of type I diabetes in nonobese diabetic mice by allogeneic BMT. Proc Natl Acad Sci USA1985; 82: 7743–7747
42.
BlankMTomerYSlavinSShoenfeldY. Induction of tolerance to experimental anti-phospholipid syndrome (APS) by syngeneic bone marrow cell transplantation. Scand J Immunol1995; 42: 226–234
43.
AdachiYEffect of bone marrow transplantation on antiphospholipid antibody syndrome in murine lupus mice. Immunobiology1995; 192: 218–230
44.
GreismanSGOcclusive vasculopathy in systemic lupus erythematosus: Association with anti-cardiolipin antibody. Arch Intern Med1991; 151: 389–392
