New developments in viral peptides and APL induction.
The associations of antiphospholipid antibodies (aPL) with thrombosis and fetal death are well recognized, but the mechanism(s) that induce their production are not. We demonstrated induction of pathogenic aPL antibodies by immunization with foreign beta(2)-GPI, or synthetic peptides representing the PL-binding site of the beta(2)-GPI. These antibodies caused intrauterine fetal death and transverse myelopathy due to spinal cord infarction in mice, and activated endothelial cells in vitro. We also introduced aPL in mice by immunization with PL-binding viral peptides and observed their pathogenic effects. This study demonstrated that pathogenic effects of aPL antibodies induced by immunization with a human CMV-derived PL-binding synthetic peptide. We hypothesize that in APS patients aPL is induced by beta(2)-GPL-like PL-binding products of human common bacteria or viruses.
Gharavi
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AE
Department of Medicine, Morehouse School of Medicine, Atlanta, GA 30310-1495, USA. aghara@pol.net
Pierangeli
S S
SS
Harris
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EN
D000595:Amino Acid Sequence; D000818:Animals; D017152:Antibodies, Antiphospholipid / Q000096:biosynthesis*; D016736:Antiphospholipid Syndrome / Q000276:immunology / Q000821:virology; D002459:Cell Fusion; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D014407:Tumor Cells, Cultured; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology*; D053482:beta 2-Glycoprotein I
D017152:Antibodies, Antiphospholipid; D006023:Glycoproteins; D010455:Peptides; D011993:Recombinant Fusion Proteins; D014764:Viral Proteins; D053482:beta 2-Glycoprotein I