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)

To investigate the pathogenic versus the protective role of cytokines and toxin-binding factors in Plasmodium falciparum infections, we measured the concentrations of tumor necrosis factor alpha, interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-1 receptor antagonist, and IL-6, as well as soluble receptors of tumor necrosis factor and IL-6 (sIL-6R) in serum of Gambian children with cerebral malaria, mild or asymptomatic malaria, or other illnesses unrelated to malaria. Because cytokine secretion may be triggered by toxic structures containing phosphatidylinositol (PI), we also measured concentrations of anti-PI antibodies and the PI-binding serum protein beta-2-glycoprotein I. We found increased concentrations of IL-6, sIL-6R, IL-1ra, and some immunoglobulin M antibodies against PI in children with cerebral malaria, but those who died had decreased concentrations of beta-2-glycoprotein I. We conclude that increased concentrations of cytokines and soluble cytokine receptors represent a normal host response to P. falciparum infections but that excessive secretion of cytokines like IL-6 may predispose to cerebral malaria and a fatal outcome while beta-2-glycoprotein I may protect against a fatal outcome of cerebral malaria.
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PMID:Increased concentrations of interleukin-6 and interleukin-1 receptor antagonist and decreased concentrations of beta-2-glycoprotein I in Gambian children with cerebral malaria. 792 98

There is increasing evidence showing that recurrent thrombosis and intrauterine fetal loss in antiphospholipid syndrome (APS) are attributable to antiphospholipid (aPL) antibodies. We have recently identified autoreactive CD4+ T cells to beta2-glycoprotein I (beta2GPI) that promote production of pathogenic antiphospholipid antibodies. beta2GPI-specific CD4+ T cells preferentially recognize the antigenic peptide containing the major phospholipid (PL)-binding site in the context of DR53. T-cell helper activity that stimulates B cells to produce IgG anti-beta2GPI antibodies is mediated through IL-6 and CD40-CD154 interaction. beta2GPI-specific T cells respond to reduced beta2GPI and recombinant beta2GPI fragments produced in a bacterial expression system but not to native beta2GPI, indicating that the epitopes recognized by beta2GPI-specific T cells are 'cryptic' determinants, which are generated at a subthreshold level by the processing of native beta2GPI under normal circumstances. Although beta2GPI-specific T cells are detected in both APS patients and healthy individuals, these autoreactive T cells are activated in vivo in APS patients but not in healthy individuals. These findings indicate activation of beta2GPI-specific T cells and subsequent production of pathogenic anti-beta2GPI antibodies can be induced by the exposure of such T cells to cryptic peptides of beta2GPI efficiently presented by functional antigen-presenting cells (APC). Delineating the mechanisms that induce the efficient processing and presentation of cryptic determinants of beta2GPI as a consequence of antigen processing would clarify the etiology that initiates the autoantibody response in APS.
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PMID:Beta2-glycoprotein I: antiphospholipid syndrome and T-cell reactivity. 1550 64

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."
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PMID:Oxidized beta2-glycoprotein I induces human dendritic cell maturation and promotes a T helper type 1 response. 1609 86

Brief virologic news included the discovery of the virophage, a unique parasite of the giant mimivirus and the association of HHV-8 infection with a peculiar form of African diabetes. Secondly, this news focused on risk factors for arterial or venous thrombosis and therapy for auto-immune disorders. Only oral estrogen therapy increases the risk of venous thromboembolism in postmenopausal women. Despite significant homocysteine lowering, vitamin supplementation with folic acid, vitamins B6 and B12 did not reduce total cardiovascular events among high-risk patients. Patients with venous thromboembolism have a substantially increased long-term risk of subsequent cardiovascular events while obesity, systemic arterial hypertension, and diabetes are common risk factors for arterial and venous thrombosis. The non fasting ApoB/ApoA1 ratio was superior to any of the cholesterol ratios for estimation of the risk of acute myocardial infection in all ethnic groups. Preventive anticoagulation of in-patients with risk of venous thromboembolism was inadequately prescribed in many hospitals of the world. Subcutaneous administration of methotrexate was more effective than the oral administration at the same dosage in patients suffering from active rheumatoid arthritis. Hydroxychloroquine directly reduces the binding of antiphospholipid antibody-beta2-glycoprotein I complexes to phospholipid bilayers. Anti-IL-5 and anti-IL-6 antibodies were effective for the treatment of respectively hypereosinophilic syndrome and rheumatoid arthritis. The efficacy of proteasome inhibitors and mesenchymal stems cells have been demonstrated in respectively two mouse strains with lupus-like disease and steroid-resistant severe acute graft-versus-host disease. These treatments may be useful for auto-immune disorders if their long term toxicity is acceptable. In conclusion, subcutaneous injections of physiological saline, used as placebo in two different trials, enhanced in vitro activation of immunocompetent cells in healthy individuals.
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PMID:[What's new in internal medicine?]. 1926 9