BMC Medicine | |
Coagulopathy triggered autoimmunity: experimental antiphospholipid syndrome in factor V Leiden mice | |
Joab Chapman3  Yehuda Shoenfeld1  Chaim G Pick5  Miri Blank1  Olga Touloumi2  Tania Ebert4  Nikolaos C Grigoriadis2  Aviva Katzav1  | |
[1] Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, affiliated to Sackler Faculty of Medicine, Tel Aviv University, Tel-Hashomer, 2 Sheba Rd, Ramat Gan, 52621, Israel;Department of Neurology, AHEPA University Hospital, Aristotle University of Thessaloniki, St. Kyriakidis 1, Thessaloniki, 54636, Greece;Department of Neurology, Sackler Faculty of Medicine, Tel Aviv University, 55 Haim Levanon St, Ramat Aviv, Tel Aviv, 69978, Israel;Beer Yaakov-Ness Ziona Mental Health Center, 1 Haim Rd, Beer Yaakov, 70350, Israel;Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv University, 55 Haim Levanon St, Ramat Aviv, Tel Aviv, 69978, Israel | |
关键词: Neurodegeneration; Cognitive dysfunction; Hyperactivity; Autoantibodies; Experimental antiphospholipid syndrome; Factor V leiden; Antiphospholipid syndrome; Coagulopathy; Autoimmunity; | |
Others : 857114 DOI : 10.1186/1741-7015-11-92 |
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received in 2012-10-18, accepted in 2013-01-31, 发布年份 2013 | |
【 摘 要 】
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 β2-glycoprotein I (β2-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 β2-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.
【 授权许可】
2013 2013 Katzav et al.; licensee BioMed Central Ltd.
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