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Blood, 15 December 2007, Vol. 110, No. 13, pp. 4312-4318.
Prepublished online as a Blood First Edition Paper on August 28, 2007; DOI 10.1182/blood-2007-07-100008.
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Submitted July 9, 2007
Accepted August 23, 2007
Excessive exposure to anionic surfaces maintains autoantibody response to 2-Glycoprotein I in patients with antiphospholipid syndrome
Yukie Yamaguchi, Noriyuki Seta, Junichi Kaburaki, Kazuko Kobayashi, Eiji Matsuura, and Masataka Kuwana*
Department of Environmental immuno-dermatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
Department of Internal Medicine, Tokyo Electric Power Company Hospital, Tokyo, Japan
Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmacuetical Sciences, Okayama, Japan
* Corresponding author; email: kuwanam{at}sc.itc.keio.ac.jp.
Antiphospholipid syndrome (APS) is an autoimmune prothrombotic disorder associated with autoantibodies to phospholipid (PL)-binding proteins, such as 2-glycoprotein I ( 2GPI). We have recently reported that binding of 2GPI to anionic PL facilitates processing and presentation of the cryptic 2GPI epitope that activates pathogenic autoreactive T cells. To clarify mechanisms that induce sustained presentation of the dominant antigenic 2GPI determinant in APS patients, T cell proliferation induced by 2GPI-treated phosphatidylserine liposome ( 2GPI/PS) was evaluated in bulk peripheral blood mononuclear cell cultures. T cells from APS patients responded to 2GPI/PS in the presence of IgG anti- 2GPI antibodies derived from APS plasma, and this response was completely inhibited either by the depletion of monocytes or by the addition of anti-Fc RI antibody. These findings indicate that efficient presentation of the cryptic determinants can be achieved by monocytes undergoing Fc RI-mediated uptake of 2GPI-bound anionic surfaces in the presence of IgG anti- 2GPI antibodies. Finally, 2GPI-bound oxidized LDL or activated platelets also induced the specific T-cell response. Continuous exposure to these anionic surfaces may play a critical role in maintaining the pathogenic anti- 2GPI antibody response in APS patients.

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