Excessive exposure to anionic surfaces maintains autoantibody response to beta(2)-glycoprotein I in patients with antiphospholipid syndrome.
Antiphospholipid syndrome (APS) is an autoimmune prothrombotic disorder associated with autoantibodies to phospholipid (PL)-binding proteins, such as beta(2)-glycoprotein I (beta(2)GPI). We have recently reported that binding of beta(2)GPI to anionic PL facilitates processing and presentation of the cryptic beta(2)GPI epitope that activates pathogenic autoreactive T cells. To clarify mechanisms that induce sustained presentation of the dominant antigenic beta(2)GPI determinant in patients with APS, T-cell proliferation induced by beta(2)GPI-treated phosphatidylserine liposome (beta(2)GPI/PS) was evaluated in bulk peripheral blood mononuclear cell cultures. T cells from patients with APS responded to beta(2)GPI/PS in the presence of immunoglobulin G (IgG) anti-beta(2)GPI antibodies derived from APS plasma, and this response was completely inhibited either by the depletion of monocytes or by the addition of anti-FcgammaRI antibody. These findings indicate that efficient presentation of the cryptic determinants can be achieved by monocytes undergoing FcgammaRI-mediated uptake of beta(2)GPI-bound anionic surfaces in the presence of IgG anti-beta(2)GPI antibodies. Finally, beta(2)GPI-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-beta(2)GPI antibody response in patients with APS.
Yamaguchi
Yukie
Y
Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Seta
Noriyuki
N
Kaburaki
Junichi
J
Kobayashi
Kazuko
K
Matsuura
Eiji
E
Kuwana
Masataka
M
D000838:Anions; D017951:Antigen Presentation; D016736:Antiphospholipid Syndrome / Q000209:etiology / Q000276:immunology*; D001323:Autoantibodies; D015551:Autoimmunity; D001792:Blood Platelets / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism; D008213:Lymphocyte Activation; D009000:Monocytes; D010718:Phosphatidylserines / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology; D053482:beta 2-Glycoprotein I / Q000276:immunology* / Q000378:metabolism
D000838:Anions; D001323:Autoantibodies; D008077:Lipoproteins, LDL; D010718:Phosphatidylserines; D053482:beta 2-Glycoprotein I; C099252:oxidized low density lipoprotein