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Coagulopathy triggered autoimmunity: experimental antiphospholipid syndrome in factor V Leiden mice.

Abstract：

BACKGROUND:We investigated interactions between genetically and autoimmune-mediated coagulopathies by inducing experimental antiphospholipid syndrome (eAPS) in mice carrying the factor V Leiden (FVL) mutation. METHODS:eAPS was induced in heterozygous and homozygous FVL transgenic mice (C57BL/6 background) by immunization with β(2)-glycoprotein I (β(2)-GPI). Autoantibody levels were measured at 1 and 5 months post-immunization. Mice were tested at 4 months post-immunization for behavior and cognitive function in the staircase, elevated plus-maze, and swim T-maze tests. Brains were removed and analyzed by immunohistochemistry for inflammatory markers and neurodegenerative processes. RESULTS:A single immunization with β(2)-GPI induced significantly higher and longer-lasting immune responses, and this was dependent on the number of FVL alleles. At 1 and 5 months post-immunization, levels of antibodies rose from 1.17 ± 0.07 to 1.62 ± 0.17 (optical density units; ODU) in homozygous FVL mice, compared with stable levels of 0.59 ± 0.17 and 0.48 ± 0.16 ODU in heterozygous FVL mice and a drop from 1.62 ± 0.21 to 0.61 ± 0.13 ODU in wild-type mice. Behavioral and cognitive clinical features of eAPS were also correlated with FVL allele load, as assessed by the elevated plus-maze (altered anxiety), staircase (hyperactivity and higher exploration), and swim T-maze (impaired learning) tests. Histological studies identified significant neurodegenerative changes in both grey and white matter in the eAPS-FVL brains. In spite of the potential interaction of two prothrombotic disease states, there were no ischemic lesions seen in this group. CONCLUSIONS:The results indicate that genetically mediated coagulopathies increase the risk of developing coagulation-targeted autoimmune responses, and suggest the importance of antibody-mediated neurodegenerative processes in the brain in APS.

journal_name

BMC Med

journal_title

BMC medicine

authors

Katzav A,Grigoriadis NC,Ebert T,Touloumi O,Blank M,Pick CG,Shoenfeld Y,Chapman J

doi

10.1186/1741-7015-11-92

subject

Has Abstract

pub_date

2013-04-04 00:00:00

pages

issn

1741-7015

pii

1741-7015-11-92

journal_volume

pub_type

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Coagulopathy triggered autoimmunity: experimental antiphospholipid syndrome in factor V Leiden mice.