PMID- 10990227
OWN - NLM
STAT- MEDLINE
DCOM- 20010125
LR  - 20061115
IS  - 0315-162X (Print)
IS  - 0315-162X (Linking)
VI  - 27
IP  - 9
DP  - 2000 Sep
TI  - Anti-beta2-glycoprotein I autoantibodies, in vitro thrombin generation, and the 
      antiphospholipid syndrome.
PG  - 2152-9
AB  - OBJECTIVE: Thrombin plays a pivotal role in the regulation of hemostasis. We 
      examined the effect of antiphospholipid (aPL) antibodies, in particular those 
      with specificity for beta2-glycoprotein I (beta2-GPI), on in vitro thrombin 
      generation, and examined the association with clinical manifestations of the 
      antiphospholipid syndrome (APS). METHODS: We studied plasma samples from 59 
      patients with aPL antibodies determined by the presence of either elevated 
      anticardiolipin (aCL) antibodies or lupus anticoagulant (LAC). Direct antibody 
      binding of IgG, IgM, and IgA to beta2-GPI and prothrombin (PT) was determined by 
      ELISA. Affinity purification of total IgG and IgG anti-B2-GPI antibodies was 
      performed using staphylococcal protein A and phospholipid liposomes. A 
      chromogenic assay was used to determine the effect of plasma samples and purified 
      autoantibodies on in vitro thrombin generation. RESULTS: Thirty-three of 59 (56%) 
      plasma samples inhibited in vitro generation of thrombin and 7/59 (12%) 
      accelerated thrombin formation. There was a strong negative correlation between 
      thrombin generation and IgG aCL (r = -0.72, p < 0.001) and IgG anti-beta2-GPI (r 
      = -0.71, p < 0.001) antibody levels, and a weaker correlation with LAC (r = 
      -0.46, p = 0.001). This association was not found with anti-PT antibodies and 
      could not be attributed to concurrent therapy with warfarin. Additional 
      experiments with affinity purified IgG antibodies indicated a dose dependent 
      inhibition of thrombin generation, which was restricted to anti-beta2-GPI 
      antibodies. Patients with a history of core clinical manifestations of the APS 
      [venous and arterial thrombosis, recurrent (> or = 2) fetal loss] had 
      significantly greater inhibition of in vitro thrombin generation (mean +/- SEM Z 
      score: -3.38 +/- 0.51 vs -1.42 +/- 0.56; p = 0.01) and higher levels of IgG aCL 
      (mean +/- SEM Z score: 8.39 +/- 1.12 vs 5.39 +/- 0.88; p = 0.04) and IgG 
      anti-beta2-GPI antibodies (mean +/- SEM Z score: 4.49 +/- 0.69 vs 2.26 +/- 0.54; 
      p = 0.01). Odds ratios for these variables and clinical manifestations of the APS 
      were 5.43, 4.17, and 3.28, respectively. CONCLUSION: aPL antibodies may 
      accelerate or inhibit the rate of in vitro thrombin formation. The predominant 
      effect is inhibition that is restricted to IgG anti-beta2-GPI antibodies and it 
      is strongly associated with clinical manifestations of the APS.
FAU - Hanly, J G
AU  - Hanly JG
AD  - Department of Medicine, Queen Elizabeth II Health Sciences Centre, and Dalhousie 
      University, Halifax, Nova Scotia, Canada. jhanly@is.dal.ca
FAU - Smith, S A
AU  - Smith SA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Canada
TA  - J Rheumatol
JT  - The Journal of rheumatology
JID - 7501984
RN  - 0 (Autoantibodies)
RN  - 0 (Glycoproteins)
RN  - 0 (beta 2-Glycoprotein I)
RN  - EC 3.4.21.5 (Thrombin)
SB  - IM
CIN - J Rheumatol. 2001 Apr;28(4):919-20. PMID: 11327278
MH  - Antiphospholipid Syndrome/*blood/*immunology
MH  - Autoantibodies/*blood/*immunology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Glycoproteins/*blood/*immunology
MH  - Humans
MH  - Thrombin/*immunology
MH  - beta 2-Glycoprotein I
EDAT- 2000/09/16 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/09/16 11:00
PHST- 2000/09/16 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/09/16 11:00 [entrez]
PST - ppublish
SO  - J Rheumatol. 2000 Sep;27(9):2152-9.