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 |
|---|---|
| Pages (from-to) | 4312-4318 |
| Number of pages | 7 |
| Journal | Blood |
| Volume | 110 |
| Issue number | 13 |
| DOIs | |
| Publication status | Published - Dec 15 2007 |
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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 journal › Article
}
TY - JOUR
T1 - Excessive exposure to anionic surfaces maintains autoantibody response to β2-glycoprotein I in patients with antiphospholipid syndrome
AU - Yamaguchi, Yukie
AU - Seta, Noriyuki
AU - Kaburaki, Junichi
AU - Kobayashi, Kazuko
AU - Matsuura, Eiji
AU - Kuwana, Masataka
PY - 2007/12/15
Y1 - 2007/12/15
N2 - 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.
AB - 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.
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U2 - 10.1182/blood-2007-07-100008
DO - 10.1182/blood-2007-07-100008
M3 - Article
VL - 110
SP - 4312
EP - 4318
JO - Blood
JF - Blood
SN - 0006-4971
IS - 13
ER -