Increase in plasma thrombin-activatable fibrinolysis inhibitor may not contribute to thrombotic tendency in antiphospholipid syndrome because of inhibitory potential of antiphospholipid antibodies toward TAFI activation
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概要
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Background: The causes of thrombosis in antiphospholipid syndrome (APS) remain unknown, though several hypotheses in regard to hypofibrinolysis have been proposed. Objective: To clarify the mechanism, we measured plasma levels of thrombin-activatable fibrinolysis inhibitor (TAFI) in APS patients. Methods and Results: Both the TAFI antigen (TAFI:Ag) level measured with an ELISA, and thrombin-thrombomodulin-dependent TAFI activity (TAFI:Ac) were elevated in 68 APS patients as compared with those in 66 healthy controls, though they were lower than those in 46 patients with autoimmune diseases. As for the influence of antiphospholipid antibodies (aPL) on TAFI levels, the mean TAFI:Ac level in 39 SLE patients positive for APS was significantly lower than that in 27 SLE patients without APS, whereas there was no difference in TAFI:Ag between those groups. Furthermore, purified IgG from patients positive for aPL, and monoclonal aPL (EY2C9 and 23-1D) inhibited the activation of TAFI in a concentration dependent manner. Conclusion: These results suggest that aPL inhibits TAFI activation by affecting the function of thrombomodulin-thrombin complex through phospholipids. Although TAFI in plasma is elevated in autoimmune diseases including APS, we concluded that an elevated level is not likely a risk factor for thrombosis in APS patients, because of the inhibition of TAFI activation by aPL.
- 2010-06-15
著者
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KOIKE Takao
Department of Internal Medicine II, Hokkaido University Graduate School of Medicine
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MUKAI Masaya
Department of Surgery, Tokai University Oiso Hospital
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IEKO Masahiro
Department of Internal Medicine, School of Dentistry, Health Sciences University of Hokkaido
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YOSHIDA Mika
Department of Clinical Laboratory, School of Dentistry, Health Sciences University of Hokkaido
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NAITO Sumiyoshi
Department of Clinical Laboratory, School of Dentistry, Health Sciences University of Hokkaido
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NAKABAYASHI Toru
Department of Internal Medicine, School of Dentistry, Health Sciences University of Hokkaido
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KANAZAWA Kaoru
Department of Oral and Maxillofacial Surgery, School of Dentistry, Health Sciences University of Hok
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MIZUKAMI Kazuhiro
Department of Orthodontics, School of Dentistry, Health Sciences University of Hokkaido
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ATSUMI Tatsuya
Department of Medicine II, Hokkaido University Graduate School of Medicine
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Yoshida Mika
Department Of Clinical Laboratory School Of Dentistry Health Sciences University Of Hokkaido
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Ieko Masahiro
Department Of Clinical Immunology And Hematology Sapporo City General Hospital
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Atsumi Tatsuya
Department Of Medicine Ii Hokkaido University Graduate School Of Medicine
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Kanazawa Kaoru
Department Of Oral And Maxillofacial Surgery School Of Dentistry Health Sciences University Of Hokka
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Koike Takao
Department Of Medicine Ii Hokkaido University Graduate School Of Medicine
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Kawamura Takahito
Department Of Medicine Ii Hokkaido University Graduate School Of Medicine
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Mukai Masaya
Department Of Clinical Immunohematology Sapporo City General Hospital
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Yoshida Mika
Department Of Chemistry And Chemical Engineering Faculty Of Engineering Niigata University
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Naito Sumiyoshi
北海道医療大学 歯学部内科学
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Naito Sumiyoshi
Department Of Clinical Laboratory School Of Dentistry Health Sciences University Of Hokkaido
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Nakabayashi Toru
北海道医療大学 歯学部内科学
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Nakabayashi Toru
Department Of Internal Medicine School Of Dentistry Health Sciences University Of Hokkaido
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Nakabayashi Toru
Department Of Internal Medicine Health Science University Of Hokkaido
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Mizukami Kazuhiro
Department Of Orthodontics School Of Dentistry Health Sciences University Of Hokkaido
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Koike Takao
Department Of Internal Medicine Ii School Of Medicine Hokkaido University
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Ieko Masahiro
北海道医療大学 歯学部内科学
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Kanazawa Kaoru
Department Of Dental Anesthesiology Health Sciences University Of Hokkaido
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Koike Takao
Department Of Internal Medicine Hokkaido University School Of Medicine
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Atsumi Tatsuya
Department Of Internal Medicine Ii Hokkaido University Graduate School Of Medicine
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KOIKE Takao
Department II, Hokkaido University Graduate School of Medicine
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