β₂-Glycoprotein-1 autoantibodies from patients with antiphospholipid syndrome are sufficient to potentiate arterial thrombus formation in a mouse model.

β₂-Glycoprotein-1 autoantibodies from patients with antiphospholipid syndrome are sufficient to potentiate arterial thrombus formation in a mouse model.

MedLine Citation:	PMID: 21245481 Owner: NLM Status: MEDLINE
Abstract/OtherAbstract:	Antiphospholipid syndrome is characterized by thrombosis, recurrent fetal loss, and the presence of the lupus anticoagulant, anticardiolipin antibodies, or anti-β(2)-glycoprotein-1 (anti-β(2)-GP1) antibodies. Although anti-β(2)-GP1 antibodies have been documented as a biomarker for diagnosis of antiphospholipid syndrome, their direct role in the pathogenesis of thrombosis is unknown. We have demonstrated using intravital microscopy that anti-β(2)-GP1 autoantibodies purified from the sera of patients with antiphospholipid syndrome complicated by thrombosis greatly amplify thrombus size after laser-induced vessel wall injury in live mice. Anti-β(2)-GP1 autoantibodies from 3 patients with antiphospholipid syndrome were affinity-purified using human β(2)-GP1 bound to agarose. The effects of purified anti-β(2)-GP1 IgG autoantibodies, of anti-β(2)-GP1-depleted IgG, and of IgG from normal human sera on thrombus formation were measured in mice after arterial injury in the cremaster muscle. Before injury, purified anti-β(2)-GP1 IgG autoantibodies, anti-β(2)-GP1 antibody-depleted IgG, or IgG from normal human sera were infused. Increasing amounts of purified anti-β(2)-GP1 autoantibodies increased thrombus size in a dose-dependent manner, whereas neither anti-β(2)-GP1 antibody-depleted IgG nor IgG from normal serum affected thrombus size. These results indicate that anti-β(2)-GP1 IgG autoantibodies in antiphospholipid syndrome patient sera are not only a marker of antiphospholipid syndrome but are directly involved in the pathogenesis of thrombosis.

Authors:	Ariela Arad; Valerie Proulle; Richard A Furie; Barbara C Furie; Bruce Furie
Publication Detail:	Type: Journal Article Date: 2011-01-18
Journal Detail:	Title: Blood Volume: 117 ISSN: 1528-0020 ISO Abbreviation: Blood Publication Date: 2011 Mar
Date Detail:	Created Date: 2011-03-25 Completed Date: 2011-06-06 Revised Date: 2012-03-26
Medline Journal Info:	Nlm Unique ID: 7603509 Medline TA: Blood Country: United States
Other Details:	Languages: eng Pagination: 3453-9 Citation Subset: AIM; IM
Affiliation:	Division of Hemostasis and Thrombosis, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115, USA.
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MeSH Terms
Descriptor/Qualifier:	Adult Animals Antiphospholipid Syndrome / blood, immunology* Arteries / pathology Autoantibodies / adverse effects, isolation & purification Disease Models, Animal Female Humans Male Mice Mice, Inbred C57BL Middle Aged Thrombosis / etiology, metabolism, pathology beta 2-Glycoprotein I / immunology, metabolism
Grant Support
ID/Acronym/Agency:	R01 HL092125-04/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:	0/Autoantibodies; 0/beta 2-Glycoprotein I
Comments/Corrections
Comment In:	Blood. 2011 Mar 24;117(12):3253-5 [PMID: 21436079 ]

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