PMID- 11315927
OWN - NLM
STAT- MEDLINE
DCOM- 20010503
LR  - 20071114
IS  - 0004-3591 (Print)
IS  - 0004-3591 (Linking)
VI  - 44
IP  - 4
DP  - 2001 Apr
TI  - Identification of an Fc gamma receptor-independent mechanism by which intravenous 
      immunoglobulin ameliorates antiphospholipid antibody-induced thrombogenic 
      phenotype.
PG  - 876-83
AB  - OBJECTIVE: Patients with the antiphospholipid antibody syndrome (APS) often 
      experience recurrent arterial and venous thrombosis and pregnancy losses. 
      Intravenous immunoglobulin (IVIG) therapy has prevented pregnancy loss in some 
      women with APS and has reversed fetal resorption rates in murine models of 
      pregnancy loss. Although the basis for these effects is unknown, effector 
      mechanisms of pathogenic antibodies often involve receptors for IgG (Fc gamma 
      receptors [Fc gammaR]). We examined the potential mechanisms of action of WIG in 
      an in vivo murine model of antiphospholipid antibody (aPL)-induced thrombosis and 
      endothelial cell activation. METHODS: Mice infused with IgG containing human 
      anticardiolipin antibodies (aCL) were treated with IVIG (36 microg i.v.), saline, 
      or ovalbumin. Surgically induced thrombus formation and in vivo leukocyte 
      adhesion to endothelial cells were measured. Circulating levels of aCL were 
      measured by enzyme-linked immunosorbent assay. To determine whether Fc gammaR are 
      required for the effects of IVIG, we treated mice deficient in stimulatory Fc 
      gammaR. To examine the effects of IVIG on endogenously generated antibody, we 
      treated mice immunized with beta2-glycoprotein I (beta2GPI). RESULTS: IVIG 
      treatment inhibited aPL-induced endothelial cell activation and enhancement of 
      thrombosis in mice passively infused with human aPL-containing IgG, and this was 
      associated with a decrease in aPL levels. Similarly, IVIG lowered aPL levels and 
      inhibited thrombogenesis in mice immunized with beta2GPI. The thrombophilic 
      effects of aPL were evident in Fc gammaR-deficient mice. CONCLUSION: Treatment 
      with IVIG inhibits the thrombogenic effects of aPL in vivo and reduces the levels 
      of aCL in the circulation. Blockade of stimulatory Fc gammaR on inflammatory 
      cells is not necessary for this effect. The mechanism of action of IVIG is more 
      likely saturation of the IgG transport receptor, leading to accelerated 
      catabolism of pathogenic aPL. These results have implications in the management 
      of thrombosis in APS and may have applications for pregnant patients with a 
      history of APS.
FAU - Pierangeli, S S
AU  - Pierangeli SS
AD  - Morehouse School of Medicine, Atlanta, Georgia 30310-1495, USA.
FAU - Espinola, R
AU  - Espinola R
FAU - Liu, X
AU  - Liu X
FAU - Harris, E N
AU  - Harris EN
FAU - Salmon, J E
AU  - Salmon JE
LA  - eng
GR  - G12-RR-03034/RR/NCRR NIH HHS/United States
GR  - GM-58268-02/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Arthritis Rheum
JT  - Arthritis and rheumatism
JID - 0370605
RN  - 0 (Antibodies, Anticardiolipin)
RN  - 0 (Glycoproteins)
RN  - 0 (Immunoglobulins, Intravenous)
RN  - 0 (Receptors, IgG)
RN  - 0 (beta 2-Glycoprotein I)
SB  - IM
CIN - Rheumatology (Oxford). 2003 Sep;42(9):1029-31. PMID: 12730514
MH  - Animals
MH  - Antibodies, Anticardiolipin/blood
MH  - Antiphospholipid Syndrome/*therapy
MH  - Disease Models, Animal
MH  - Endothelium, Vascular/immunology
MH  - Glycoproteins/pharmacology
MH  - Immunization, Passive
MH  - Immunoglobulins, Intravenous/*therapeutic use
MH  - Lymphocyte Activation
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Receptors, IgG/deficiency/genetics/*immunology
MH  - Thrombosis/*therapy
MH  - beta 2-Glycoprotein I
EDAT- 2001/04/24 10:00
MHDA- 2001/05/05 10:01
CRDT- 2001/04/24 10:00
PHST- 2001/04/24 10:00 [pubmed]
PHST- 2001/05/05 10:01 [medline]
PHST- 2001/04/24 10:00 [entrez]
AID - 10.1002/1529-0131(200104)44:4<876::AID-ANR144>3.0.CO;2-2 [doi]
PST - ppublish
SO  - Arthritis Rheum. 2001 Apr;44(4):876-83. doi: 
      10.1002/1529-0131(200104)44:4<876::AID-ANR144>3.0.CO;2-2.