PMID- 21781264
OWN - NLM
STAT- MEDLINE
DCOM- 20111201
LR  - 20230829
IS  - 1538-7836 (Electronic)
IS  - 1538-7836 (Linking)
VI  - 9 Suppl 1
DP  - 2011 Jul
TI  - Molecular pathophysiology of the antiphospholipid syndrome: the role of oxidative 
      post-translational modification of beta 2 glycoprotein I.
PG  - 275-82
LID - 10.1111/j.1538-7836.2011.04301.x [doi]
AB  - It has been well established that antiphospholipid antibodies and specifically 
      those directed against beta 2 glycoprotein I (beta2GPI) are pathogenic for the 
      development of thrombosis in the antiphospholipid syndrome (APS). Several groups 
      have shown that anti-beta2GPI antibodies, in complex with beta2GPI, elicit effects on 
      blood cells and coagulation-fibrinolysis proteins, which prime the arterial and 
      venous vasculature for the development of thrombosis. However, much less is known 
      about the mechanism initiating the production of autoantibodies against beta2GPI, a 
      physiological abundant protein of blood. In the current review, novel findings 
      are presented regarding the structure and oxidative post-translational 
      modifications of beta2GPI, which trigger the immune response. The majority of 
      circulating beta2GPI exists in a form containing unpaired cysteines (free thiols), 
      which constitutes the reduced form of beta2GPI. The free thiols exposed on beta2GPI are 
      involved in the interaction with platelets and endothelial cells. We propose that 
      this abundant pool of free thiols may serve as an antioxidant reservoir 
      protecting cells or critical molecules from oxidative stress. Oxidation of beta2GPI 
      confers an increase in its immunogenicity through a Th1 immunological mechanism. 
      The clinical significance of these observations is that serum from patients with 
      APS, assessed by a novel ELISA assay, have a significant increase in oxidised 
      beta2GPI. These findings hold promise, not only for the delineation of the role of 
      beta2GPI as an immunological target, but also for the development of improved 
      diagnostic and prognostic assays for APS.
CI  - (c) 2011 International Society on Thrombosis and Haemostasis.
FAU - Passam, F H
AU  - Passam FH
AD  - Department of Immunology, Allergy and Infectious Diseases, St George Hospital, 
      University of New South Wales, Sydney, Australia.
FAU - Giannakopoulos, B
AU  - Giannakopoulos B
FAU - Mirarabshahi, P
AU  - Mirarabshahi P
FAU - Krilis, S A
AU  - Krilis SA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - England
TA  - J Thromb Haemost
JT  - Journal of thrombosis and haemostasis : JTH
JID - 101170508
RN  - 0 (Antibodies, Antiphospholipid)
RN  - 0 (beta 2-Glycoprotein I)
SB  - IM
MH  - Antibodies, Antiphospholipid/blood
MH  - Antiphospholipid Syndrome/*genetics
MH  - Humans
MH  - Oxidation-Reduction
MH  - *Protein Processing, Post-Translational
MH  - beta 2-Glycoprotein I/*metabolism
EDAT- 2011/08/04 06:00
MHDA- 2011/12/13 00:00
CRDT- 2011/07/26 06:00
PHST- 2011/07/26 06:00 [entrez]
PHST- 2011/08/04 06:00 [pubmed]
PHST- 2011/12/13 00:00 [medline]
AID - S1538-7836(22)05513-1 [pii]
AID - 10.1111/j.1538-7836.2011.04301.x [doi]
PST - ppublish
SO  - J Thromb Haemost. 2011 Jul;9 Suppl 1:275-82. doi: 
      10.1111/j.1538-7836.2011.04301.x.