Excessive exposure to anionic surfaces maintains autoantibody response to β2-glycoprotein I in patients with antiphospholipid syndrome

Yukie Yamaguchi, Noriyuki Seta, Junichi Kaburaki, Kazuko Kobayashi, Eiji Matsuura, Masataka Kuwana

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Antiphospholipid syndrome (APS) is an autoimmune prothrombotic disorder associated with autoantibodies to phospholipid (PL)-binding proteins, such as β2-glycoprotein I (β2GPI). We have recently reported that binding of β2GPI to anionic PL facilitates processing and presentation of the cryptic β2GPI epitope that activates pathogenic autoreactive T cells. To clarify mechanisms that induce sustained presentation of the dominant antigenic β2GPI determinant in patients with APS, T-cell proliferation induced by β2GPI-treated phosphatidylserine liposome (β 2GPI/PS) was evaluated in bulk peripheral blood mononuclear cell cultures. T cells from patients with APS responded to β2GPI/PS in the presence of immunoglobulin G (IgG) anti-β2GPI antibodies derived from APS plasma, and this response was completely inhibited either by the depletion of monocytes or by the addition of anti-FcγRI antibody. These findings indicate that efficient presentation of the cryptic determinants can be achieved by monocytes undergoing FcγRI-mediated uptake of β2GPI-bound anionic surfaces in the presence of IgG anti-β2GPI antibodies. Finally, β2GPI-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-β2GPI antibody response in patients with APS.

Original languageEnglish
Pages (from-to)4312-4318
Number of pages7
JournalBlood
Volume110
Issue number13
DOIs
Publication statusPublished - Dec 15 2007

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Antiphospholipid Syndrome
Autoantibodies
Glycoproteins
T-cells
T-Lymphocytes
Antibodies
Monocytes
Phospholipids
Immunoglobulin G
Phosphatidylserines
Cell proliferation
Platelets
Cell culture
Liposomes
Antibody Formation
Epitopes
Anti-Idiotypic Antibodies
Blood Cells
Carrier Proteins
Blood

ASJC Scopus subject areas

  • Hematology

Cite this

Excessive exposure to anionic surfaces maintains autoantibody response to β2-glycoprotein I in patients with antiphospholipid syndrome. / Yamaguchi, Yukie; Seta, Noriyuki; Kaburaki, Junichi; Kobayashi, Kazuko; Matsuura, Eiji; Kuwana, Masataka.

In: Blood, Vol. 110, No. 13, 15.12.2007, p. 4312-4318.

Research output: Contribution to journalArticle

Yamaguchi, Yukie ; Seta, Noriyuki ; Kaburaki, Junichi ; Kobayashi, Kazuko ; Matsuura, Eiji ; Kuwana, Masataka. / Excessive exposure to anionic surfaces maintains autoantibody response to β2-glycoprotein I in patients with antiphospholipid syndrome. In: Blood. 2007 ; Vol. 110, No. 13. pp. 4312-4318.
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