Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02749 (beta2-glycoprotein I)
 836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We present the clinical characteristics of pregnancy histories and subsequent pregnancy outcomes of 13 women who tested positive for anticardiolipin beta2-glycoprotein I antibody (aCLbeta2GPI). Six of the 13 women had a history of recurrent spontaneous abortion (RSA). The prevalence of aCLbeta2GPI syndrome among women with RSA was very low (2.1%). Other women with aCLbeta2GPI were identified by the presence of a biological false-positive serological test for syphilis, intrauterine growth restriction (IUGR), and a history of thrombosis. However, serum aCLbeta2GPI titers in the 13 women varied, with a wide range from 3.6 to 1468 U/mL. Their pregnancy histories, subsequent pregnancy outcomes, and complications were compared according to the classification of serum aCLbeta2GPI titers as low, moderate, or high. The history of second trimester fetal death was found only in women with high serum aCLbeta2GPI titers. All women with high serum aCLbeta2GPI titers experienced severe maternal-fetal complications such as IUGR, fetal distress, systemic thromboembolism, and neonatal sequelae in subsequent pregnancies.
Semin Thromb Hemost 2003 Dec
PMID:Anticardiolipin beta2-glycoprotein I antibody: is a high titer related to unfavorable pregnancy outcome? 1471 80

Progression through mitosis requires activation of cyclin B/Cdk1 and its downstream targets, including Polo-like kinase and the anaphase-promoting complex (APC), the ubiquitin ligase directing degradation of cyclins A and B. Recent evidence shows that APC activation requires destruction of the APC inhibitor Emi1. In prophase, phosphorylation of Emi1 generates a D-pS-G-X-X-pS degron to recruit the SCF(betaTrCP) ubiquitin ligase, causing Emi1 destruction and allowing progression beyond prometaphase, but the kinases directing this phosphorylation remain undefined. We show here that the polo-like kinase Plk1 is strictly required for Emi1 destruction and that overexpression of Plk1 is sufficient to trigger Emi1 destruction. Plk1 stimulates Emi1 phosphorylation, betaTrCP binding, and ubiquitination in vitro and cyclin B/Cdk1 enhances these effects. Plk1 binds to Emi1 in mitosis and the two proteins colocalize on the mitotic spindle poles, suggesting that Plk1 may spatially control Emi1 destruction. These data support the hypothesis that Plk1 activates the APC by directing the SCF-dependent destruction of Emi1 in prophase.
Mol Biol Cell 2004 Dec
PMID:Plk1 regulates activation of the anaphase promoting complex by phosphorylating and triggering SCFbetaTrCP-dependent destruction of the APC Inhibitor Emi1. 1546 84

Complement receptor 2-deficient (Cr2(-/-)) mice are resistant to mesenteric ischemia/reperfusion (I/R) injury because they lack a component of the natural Ab repertoire. Neither the nature of the Abs that are involved in I/R injury nor the composition of the target Ag, to which recognition is lacking in Cr2(-/-) mice, is known. Because anti-phospholipid Abs have been shown to mediate fetal growth retardation and loss when injected into pregnant mice, we performed experiments to determine whether anti-phospholipid Abs can also reconstitute I/R injury and, therefore, represent members of the injury-inducing repertoire that is missing in Cr2(-/-) mice. We demonstrate that both murine and human monoclonal and polyclonal Abs against negatively charged phospholipids can reconstitute mesenteric I/R-induced intestinal and lung tissue damage in Cr2(-/-) mice. In addition, Abs against beta2 glycoprotein I restore local and remote tissue damage in the Cr2(-/-) mice. Unlike Cr2(-/-) mice, reconstitution of I/R tissue damage in the injury-resistant Rag-1(-/-) mouse required the infusion of both anti-beta2-glycoprotein I and anti-phospholipid Ab. We conclude that anti-phospholipid Abs can bind to tissues subjected to I/R insult and mediate tissue damage.
J Immunol 2004 Dec 01
PMID:Anti-phospholipid antibodies restore mesenteric ischemia/reperfusion-induced injury in complement receptor 2/complement receptor 1-deficient mice. 1555 3

Adsorption of serum proteins to the liposomal surface plays a critical role in liposome clearance from the blood. The aim of this study was to investigate the role of liposome-adsorbed serum proteins in the interaction of liposomes with hepatocytes. We analyzed the serum proteins adsorbing to the surface of differently composed small unilamellar liposomes during incubation with human or rat serum, and found that one protein, with a molecular weight of around 55 kDa, adsorbed in a large amount to negatively charged liposomes containing phosphatidylserine (PS) or phosphatidylglycerol (PG). The binding was dependent on the liposomal charge density. The approximately 55-kDa protein was identified as beta2-glycoprotein I (beta2GPI) by Western blotting. Despite the high affinity of beta2GPI for strongly negatively charged liposomes, in vitro uptake and binding experiments with isolated rat hepatocytes, Kupffer cells or liver endothelial cells, and with HepG2 cells showed no enhancing effect of this protein on the association of negatively charged liposomes with any of these cells. On the contrary, an inhibitory effect was observed. We conclude that despite abundant adsorption to negatively charged liposomes, beta2GP1 inhibits, rather than enhances, liposome uptake by liver cells.
Biochim Biophys Acta 2004 Dec 15
PMID:The role of beta2-glycoprotein I in liposome-hepatocyte interaction. 1558 57

Human beta2-glycoprotein I (beta2gpI) is a phospholipid and heparin binding plasma glycoprotein involved in autoimmune diseases characterized by blood clotting disturbances (thrombosis) together with the occurrence of autoantibodies against beta2gpI. With the final goal of assessing autoantibody influence on binding interactions of beta2gpI we have studied the development of capillary electrophoresis (CE)-based assays for interactions of negatively charged ligands with beta2gpI. In the development of suitable conditions for analysis at neutral pH of this basic protein (pI about 8) we found the pH hysteresis behavior of fused silica surfaces useful since the protonated surface after an acid pre-wash counteracted protein adsorption efficiently in contrast to more laborious procedures including acrylamide/dimethylacrylamide coatings that did not permit analysis of this particular protein. This simple approach made estimates of heparin-beta2gpI interactions possible and the principle was shown also to work for detection of betagpI binding to anionic phospholipids. Utilizing the pH hysteresis effect may be a simple solution to the adsorption problems often encountered in analyses of proteins by CE.
J Chromatogr A 2004 Dec 03
PMID:Capillary electrophoresis-based analysis of phospholipid and glycosaminoglycan binding by human beta2-glycoprotein I. 1562 44

The human plasma protein beta2-glycoprotein I (beta2-GPI) is the most common target for antiphospholipid antibodies associated with thrombotic events in chronic disorders related to endothelial cell dysfunction. Crucial information is needed to clarify why this self-abundant protein is targeted by autoimmune responses. In this study, we investigated whether oxidative modification of beta2-GPI, either spontaneous in culture wells or induced by treatment with H2O2, renders this self-protein able to activate immature monocyte-derived dendritic cells (DCs) from healthy human donors. Oxidized beta2-GPI caused DCs to mature so that CD83 appeared and CD80, CD86, human leukocyte antigen-D region related (HLA-DR), and CD40 increased. The interaction between oxidized beta2-GPI and DCs specifically stimulated these cells to secrete interleukin 12 (IL-12), IL-1beta, IL-6, IL-8, tumor necrosis factor alpha (TNF-alpha), and IL-10. Oxidized beta2-GPI-stimulated DCs had increased allostimulatory ability and primed naive T lymphocytes, thus inducing T helper 1 (Th1) polarization. The interaction between oxidized beta2-GPI and DCs involved interleukin-1 receptor associated kinase (IRAK) phosphorylation and nuclear factor kappaB (NFkappaB) activation. Pretreatment of beta2-GPI with the antioxidant alpha-tocopherol prevented DC maturation. These findings show that human oxidized beta2-GPI, probably by interacting with a member of the Toll-like receptor (TLR) family, causes DCs to mature. Because this key beta2-GPI function requires oxidative modification, in several chronic disorders related to endothelial cell dysfunction oxidative stress might trigger the "autoimmune spiral."
Blood 2005 Dec 01
PMID:Oxidized beta2-glycoprotein I induces human dendritic cell maturation and promotes a T helper type 1 response. 1609 86

Study objectives were to determine, in children with systemic lupus erythematosus (SLE), (1) the association of antiphosholipid antibody (APLA) subtypes with thrombotic events (TEs) and (2) the predictive value of persistent versus transient antibodies for TEs. This is a cohort study of 58 SLE children in whom lupus anticoagulants (LAs), anticardiolipin antibodies (ACLAs), anti-beta2-glycoprotein-I (anti-beta2-GPI), and antiprothrombin (anti-PT) were assessed on at least 2 occasions (more than 3 months apart). Antibodies were classified as persistent (positive on at least 2 occasions) or transient (positive once). Outcomes were symptomatic TEs confirmed by objective radiographic tests identified retrospectively and prospectively. Seven of the 58 patients (12%) had 10 TEs; 5 patients had TEs during prospective follow-up. Persistent LAs showed the strongest association with TEs (P < .001). Persistent ACLAs (P = .003) and anti-beta2-GPI (P = .002) were significantly associated with TEs; anti-PT (P = .063) showed a trend. Persistent or transient LAs and anti-beta2-GPI showed similar strength of association, while ACLAs and anti-PT were no longer associated with TEs. Positivity for multiple APLA subtypes showed stronger associations with TEs than for individual APLA subtypes because of improved specificity. Lupus anticoagulant is the strongest predictor of the risk of TEs; other APLA subtypes provide no additional diagnostic value. Anticardiolipin antibodies and anti-PT require serial testing because only persistent antibodies are associated with TEs.
Blood 2005 Dec 15
PMID:Predictive value of persistent versus transient antiphospholipid antibody subtypes for the risk of thrombotic events in pediatric patients with systemic lupus erythematosus. 1614 97

Several inflammatory and immunological factors have been established as important contributors to atherogenesis. Among these, oxidized low-density lipoprotein (oxLDL) play a central role in the initiation and progression of atherosclerotic lesions. In atherosclerotic lesions, oxLDL was also found to co-localize with beta2-glycoprotein I (beta2-GPI). Immunoglobulin (Ig)G autoantibodies against beta2-GPI complexed with oxLDL are pro-atherogenic because they increase uptake of the complexes by macrophages. In contrast, IgM natural anti-oxLDL antibodies derived from atherosclerosis-prone apolipoprotein E (ApoE) deficient mice reduced incidence of atherosclerosis. Such anti-oxLDL antibodies have been found in humans, and the accumulating evidences seem to support the idea that anti-oxLDL antibodies have a protective role for atherogenesis. Intravenous immunoglobulins (IVIgs) contain natural anti-oxLDL antibodies and infusion of IVIg into ApoE-deficient mice has been reported to decrease atherosclerosis. The anti-atherogenic property of IVIg may be derived from non-antigen-specific antibody binding to FCgamma receptors, which blocks foam cell formation of macrophages. Several other possible mechanisms are also discussed.
Clin Rev Allergy Immunol 2005 Dec
PMID:Intravenous immunoglobulin and atherosclerosis. 1639 7

Intravenous immunoglobulin (IVIg) has been used to prevent pregnancy loss, in unexplained recurrent miscarriage, and in antiphospholipid syndrome (APS). When used on an unselected population with recurrent miscarriage, IVIg has not been shown to improve the live birth rate. However, when patients are selected for poor prognosis or autoimmune phenomena, IVIg has been shown to be effective. This article discusses the possible immune mechanisms by which IVIg may act and the effect of confounding factors such as embryonic chromosomal aberrations or anti-beta2-glycoprotein I antibodies in APS. Hence, there may be an impression of futility, when IVIg may be highly effective in saving those pregnancies that can be saved. Additionally, in an unselected population with recurrent miscarriage, there is a relatively good prognosis for a subsequent live birth (60%). Therefore, the spontaneous prognosis must be taken into account, which has not been the case in previous trials.
Clin Rev Allergy Immunol 2005 Dec
PMID:Intravenous immunoglobulin and recurrent pregnancy loss. 1639 9

The antiphospholipid syndrome is an autoimmune condition in which venous or arterial thrombosis is a primary clinical feature. The other primary clinical feature is adverse pregnancy outcome, specifically recurrent miscarriage, fetal death, or preterm delivery due to severe preeclampsia or placental insufficiency. The diagnostic autoantibodies for antiphospholipid syndrome are lupus anticoagulant, anticardiolipin, or anti-beta2-glycoprotein I.
Clin Obstet Gynecol 2006 Dec
PMID:Antiphospholipid syndrome and thrombosis. 1708 81


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