Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.6 (thromboplastin)
 13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine whether the anti-cardiolipin antibodies are identical with the lupus anticoagulant and other antibodies to phospholipids and DNA, we prepared monoclonal hybridoma autoantibodies to cardiolipin from SLE-prone MRL/lpr mice and characterized their specificity. Using a somatic cell hybridization technique, we established three hybridoma clones which produce antibodies to cardiolipin (CAL-1: IgG2b, k, CAL-2: IgM, k and CAL-3: IgM, k). These hybridoma antibodies preferentially reacted with cardiolipin and phosphatidylserine, weakly reacted with phosphatidylinositol, but not with other phospholipids such as phosphatidylcholine, sphingomyelin, phosphatidylethanolamine and VDRL antigen. Two hybridoma anti-cardiolipin antibodies bound to ssDNA and were found to act as the lupus anticoagulant when mixing activated partial thromboplastin time with cephalin. These autoantibodies may prove to be good tools for elucidating mechanisms of thrombosis, thrombocytopenia, fetal loss and other related manifestations found in patients with systemic lupus erythematosus.
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PMID:Monoclonal hybridoma anti-cardiolipin antibodies from SLE mice. 314 52

Antiphospholipid syndrome is characterized by the presence of high titers of anti-beta(2)-glycoprotein I (beta(2)GPI) antibodies, lupus anticoagulant associated with thromboembolic phenomena, thrombocytopenia and recurrent fetal loss. Single-chain Fv (scFv) were prepared from four anti-beta(2)GPI mAb, CAM, CAL, CAR and 2C4C2, and one anti-ssDNA. All five scFv showed the same antigen binding properties as the original mAb. Replacement of the pathogenic CAM V(H) domain with the non-pathogenic CAL V(H) or anti-ssDNA V(H) decreased the binding affinity of the scFv to beta(2)GPI and completely abrogated the anticoagulant activity. Exchanging the CAM V(H) with anti-DNA V(H) resulted in a shift from anti-beta(2)GPI to anti-ssDNA binding of the scFv. Replacement of the CAM V(L) with CAL V(L) did not affect the binding and activity. BALB/c mice were immunized with the anti-beta(2)GPI scFv, and the scFv resulting from the substitution of the heavy (H) and light (L) chains. The mice which were immunized with CAM, 2C4C2 and CAR scFv developed clinical manifestations of experimental anti-phospholipid syndrome. Elevated titers of mouse anti-cardiolipin (aCL), anti-beta(2)GPI, associated with lupus anticoagulant activity, thrombocytopenia, prolonged activated partial thromboplastin time and a high percentage of fetal resorptions were detected, in the CAM scFv group and in the scFv composed of CAM V(H) groups. High titers of aCL, anti-beta(2)GPI, anti-ss/dsDNA and anti-histone associated with lupus findings were observed in the sera of the 2C4C2 scFv-immunized mice. Immunization with CAL scFv did not lead to any clinical findings. The current study shows that scFv of pathogenic antibodies are capable of inducing the same clinical manifestations as the whole antibody molecule upon active immunization. Replacement of H/L chains point to the importance of the V(H) domains in the pathogenic potential of anti-beta(2)GPI.
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PMID:Characteristics and pathogenic role of anti-beta2-glycoprotein I single-chain Fv domains: induction of experimental antiphospholipid syndrome. 1059 Feb 57