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 language | English |
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Pages (from-to) | 4312-4318 |
Number of pages | 7 |
Journal | Blood |
Volume | 110 |
Issue number | 13 |
DOIs | |
Publication status | Published - Dec 15 2007 |
ASJC Scopus subject areas
- Biochemistry
- Immunology
- Hematology
- Cell Biology