Induction of experimental anti-phospholipid syndrome associated with SLE following immunization with human monoclonal pathogenic anti-DNA idiotype

Blank, Miri; Krause, Ilan; Ben-Bassat, M; Shoenfeld, Yehuda

doi:10.1016/0896-8411(92)90008-e

Cited by 78 publications

(38 citation statements)

References 24 publications

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“…After mating, they exhibited fetal loss (10,12). In another set ofexperiments, the APLS model was passively induced by an intravenous transfusion ofserum anticardiolipin antibodies (24 h after mating), and similar results were obtained when the mice were mated (1 1).…”

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confidence: 48%

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Prevention of fetal loss in experimental antiphospholipid syndrome by in vivo administration of recombinant interleukin-3.

Fishman

Falach-Vaknine²,

Zigelman³

et al. 1993

J. Clin. Invest.

135

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Antiphospholipid antibodies are strongly associated with arterial and venous thrombosis and with fetal loss. Recently an experimental model for antiphospholipid syndrome (APLS) was established in our laboratory. In this model, mice are immunized passively or actively with anticardiolipin antibodies and acquire the syndrome, which is characterized by prolonged activated partial thromboplastin time (APTT), thrombocytopenia, low fecundity rate, and fetal loss.In a normal process of pregnancy, lymphokines affect fetal implantation and development. Cytokines from the colony stimulating factor family, like GM-CSF and IL-3, were shown to be positive signals for implantation and to promote placental development and fetal growth.Given our preliminary findings of low IL-3 in mice with APLS and the efficacy of IL-3 in preventing fetal loss in a strain of mice prone to fetal resorption, our aim in the present study was to examine the effect of murine recombinant IL-3 (mrIL-3) on pregnant mice induced with experimental APLS. Mice were passively transfused to the tail vein, 24 h following mating, with anticardiolipin antibodies. The mice were divided into two groups: one group was injected intraperitoneally with mrIL-3 on days 6.5, 8.5, and 10.5 after mating, while the control group was injected with PBS. When the mice were killed on day 15 of pregnancy a 32%±4.2 resorption rate was observed in the anti-cardiolipin-immunized group, which was reduced to 4%±0.3 following treatment with mrIL-3. The thrombocytopenia associated with the experimental APLS was also corrected following lymphokine administration. IL-3 may be effective in prevention of recurrent fetal loss in APLS. (J. Clin.

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confidence: 48%

“…Recently, two experimental models of antiphospholipid syndrome (APLS)' were established in our laboratory (10)(11)(12).…”

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confidence: 99%

Prevention of fetal loss in experimental antiphospholipid syndrome by in vivo administration of recombinant interleukin-3.

Fishman

Falach-Vaknine²,

Zigelman³

et al. 1993

J. Clin. Invest.

135

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“…Coincident with expression of Ab 3 , immunized mice often develop an overt autoimmune condition that resembles the human disorder from which the inducing autoantibody (Ab 1 ) was obtained, e.g. systemic lupus erythematosus (SLE) in mice immunized with anti-DNA [22][23][24][25][26][27][28], antiphospholipid syndrome (APS) in mice immunized with anti-cardiolipin [24][25][26], and vasculitis in mice immunized with classical anti-neutrophil cytoplasmic antibody (C-ANCA) [31,32]. This method may be used to elicit an autoimmune phenomenon which may not be recapitulated through passive immunization of the autoantibody (Ab 1 ).…”

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confidence: 99%

Pathogenicity of human anti-platelet factor 4 (PF4)/heparin in vivo: generation of mouse anti-PF4/heparin and induction of thrombocytopenia by heparin

Blank

Cines

Arepally

et al. 1997

Clinical and Experimental Immunology

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SUMMARYHeparin-induced thrombocytopenia/thrombosis (HIT) is a severe thrombotic disorder that occurs in Ϸ1% of patients treated with heparin. Affected patients commonly develop antibodies that recognize PF4/heparin complexes that may form on the surface of activated platelets and on the endothelium. However, it has not been established that anti-PF4/heparin antibodies are responsible for the clinical manifestations of HIT. To address this issue, we employed a recently developed model of active immunity to study the effect of IgG anti-

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“…alopecia, proteinuria and deposition of immunoglobulins in the mesangium of the kidneys [14]. Recently, we have also reported on the induction of experimental anti-phospholipid syndrome associated with SLE ('secondary anti-phospholipid syndrome') following immunization with a different pathogenic human anti-DNA MoAb (MIV-7) (5]. The availability of these experimental models enabled us to evaluate various therapeutic modalities including hormonal manipulation, treatment with a drug that raises lL-2 levels (AS-101).…”

Section: Introductionmentioning

confidence: 99%

Suppression of experimental systemic lupus erythematosus (SLE) with specific anti-idiotypic antibody–saporin conjugate

Blank¹,

Manosroi

Tomer³

et al. 1994

Clinical and Experimental Immunology

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SUMMARYThe importance of the idiotypic tietwork is represented in experimental SLE induced by active immunization of naive mice with an anti-DNA idiotype (Abl) emulsified in adjuvant. The mice after 4 months of incubation generate Ab3 having anti-DNA activity. In addition, the mice develop other serologicai markers for SLE associated with clinical and histopathological manifestations characteristic ofthe disease. To confirm further the etiological role ofthe idiotype in this experimental modeL the mice were treated with specific anti-idiotypic antibodies (anti-id) which were also conjugated to a toxin-saporin (Immunotoxin (IT)). Pretreatment of hybridoma cell line producing the anti-anti-Id (anti-DNA = (Ab3)) for 48 h with the anti-Id MoAb (Ab2) reduced the production of anti-DNA by 58%, while pretreatment with the IT resulted in 86% decrease in anti-DNA secretion (saporin alone had only 12% effect). The anti-Id MoAb had no effect on the production of immunoglobutin by an unrelated eel! line. In v(vo treatment of mice with experimental SLE led to a significant decrease in titres ofserum autoantibodies, with diminished clinical manifestations. The results were more remarkable when the IT was employed. These suppressive effects were specific, since an anti-Id treatment of experimental anti-phospholipid syndrome was of no avail. The anti-Id effect was mediated via a reduction in specific anti-DNA antibody-forming cells, and lasted only while anti-Id injections were given. Discontinuation of the anti-Id injection was followed by a rise in titres of anti-DNA antibodies. No immunological escape of new anti-DNA Ids was noted. Our results point to the importance of pathogenic idiotypes in SLE and to the specific potential of implementing anti-idiotypic therapy, enhanced by the conjugation of the anti-Id to an immunotoxin. in particular one with low spontaneous toxicity.

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Induction of experimental anti-phospholipid syndrome associated with SLE following immunization with human monoclonal pathogenic anti-DNA idiotype

Cited by 78 publications

References 24 publications

Prevention of fetal loss in experimental antiphospholipid syndrome by in vivo administration of recombinant interleukin-3.

Prevention of fetal loss in experimental antiphospholipid syndrome by in vivo administration of recombinant interleukin-3.

Pathogenicity of human anti-platelet factor 4 (PF4)/heparin in vivo: generation of mouse anti-PF4/heparin and induction of thrombocytopenia by heparin

Suppression of experimental systemic lupus erythematosus (SLE) with specific anti-idiotypic antibody–saporin conjugate

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