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)

Factor XIII is a plasma protein that participates in the final stages of blood coagulation. The complete amino acid sequence of the b subunit of human factor XIII was determined by a combination of cDNA cloning and amino acid sequence analysis. A lambda gt11 cDNA library prepared from human liver mRNA was screened with an affinity-purified antibody against the b subunit of human factor XIII. Nine positive clones were isolated from 2 X 10(6) phage and plaque-purified. The largest cDNA insert was sequenced and shown to contain 2180 base pairs coding for a portion of the leader sequence (19 amino acids), the mature protein (641 amino acids), a stop codon (TGA), a 3' noncoding region (187 nucleotides), and a poly(A) tail. When the b subunit of human factor XIII was digested with cyanogen bromide, nine peptides were isolated by gel filtration and reverse-phase high-performance liquid chromatography. Amino acid sequence analyses of these peptides were performed with an automated sequenator, and 299 amino acid residues were identified. These amino acid sequences were in complete agreement with the amino acid sequence predicted from the cDNA. The b subunit of factor XIII contained 10 repetitive homologous segments, each composed of about 60 amino acids and 4 half-cystine residues. Each of these repeated segments is a member of a family of repeats present in human beta 2-glycoprotein I, complement factor B, and haptoglobin alpha 1 chain. Three potential Asn-linked carbohydrate attachment sites were also identified in the b subunit of factor XIII.
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PMID:Amino acid sequence of the b subunit of human factor XIII, a protein composed of ten repetitive segments. 302 Nov 94

The family of antiphospholipid antibodies includes antibodies binding to cardiolipin in serological test for syphilis, antibodies prolonging the clotting time in lupus anticoagulant test, antibodies reacting with plasma phospholipid-binding proteins, such as beta 2-glycoprotein I and prothrombin, and antibodies binding to oxidized low-density lipoprotein (LDL). Antiphospholipid antibodies are traditionally associated with arterial and venous thrombosis in patients with primary or secondary antiphospholipid syndrome. The recent studies, especially those on patients with myocardial infarction, extend the concept of antiphospholipid antibodies, and suggest that they play a role also in atherosclerosis. Based on the clinical studies and immunological findings, it seems that the differences in the specificity of antiphospholipid antibodies may reflect to their pathogenetic mechanisms and, finally, to their clinical consequences. The present review suggests that antibodies to oxidized LDL may not interfere directly with blood coagulation, but seem to have importance in the inflammation of the vessel wall in atherosclerosis and in vasculitis. Instead, antibodies to beta 2-glycoprotein I and to prothrombin show a closer association with thrombosis. It is possible that in the atherosclerotic plaque, the plasma proteins, such as beta 2-glycoprotein I or prothrombin, are bound to the endothelial surface and antibodies to cryptic epitopes revealed in these proteins are induced. These antibodies may contribute to the formation of atherosclerotic thrombosis by changing the balance of haemostasis toward hypercoagulative state.
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PMID:Antiphospholipid antibodies and atherosclerosis. 890 78

Recent data suggests that autoimmune factors play an important role in the pathogenesis of atherosclerosis. In this context several autoantigens have been shown to elicit an immune response that results in accelerated atherosclerotic plaque formation. In the present study, we investigated whether elevated titers of anti-oxidized low density lipoprotein (oxLDL), anticardiolipin and antibodies to beta2-glycoprotein I (beta2GPI) can predict subsequent restenosis in patients undergoing percutaneous transluminal coronary angioplasty (PTCA). A total of 74 consecutive patients (52 males, 22 females) with coronary artery disease were enrolled in the study. All patients underwent successful PTCA prior to which blood was drawn for the antibody analysis. The PTCA was followed by a clinical evaluation. Patients with recurrent chest pains underwent a repeated angiography and 34 of the 74 patients (46%) experienced restenosis. Patients positive for the presence of anti-oxLDL antibodies were more likely to develop restenosis within 6 months when compared with patients with no subsequent restenosis (relative-risk of 1.87; P< 0.05). Presence of anti-oxLDL antibodies was associated with hyperlipidemia (r = 0.25; P < 0.05) but not with other risk factors for atherosclerosis. Positivity for anticardiolipin or anti-beta2GPI antibodies which associate with a prothrombotic state, was not effective in predicting lumen narrowing. Thus, the presence of elevated levels of anti-oxLDL antibodies is associated with a higher risk for coronary restenosis following PTCA.
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PMID:Anti-oxidized low density lipoprotein antibody determination as a predictor of restenosis following percutaneous transluminal coronary angioplasty. 1042 30

Recent studies have suggested that antiphospholipid antibodies contribute to the development of atherothrombosis by enhancing atherogenesis and/or by interfering with blood coagulation. The antigenic targets of antiphospholipid antibodies are cardiolipin, oxidized LDL, beta2-glycoprotein I, or prothrombin. Oxidized LDL and beta2-glycoprotein I are found in the atherosclerotic plaque and antibodies to these proteins enhance in vitro the accumulation of modified LDL into macrophages. Autoantibodies binding to modified LDL, cardiolipin and prothrombin have been associated with atherosclerosis and its thrombotic complications in sero-epidemiological studies. These autoantibodies can be used as markers of atherosclerosis but their possible pathogenic role in the athero- and thrombogenesis needs further studies.
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PMID:Autoantibodies to modified LDLs and other phospholipid-protein complexes as markers of cardiovascular diseases. 1076 55

We have made consecutive studies to prove that autoimmune factors can influence the progression of atherosclerosis in inbred and transgenic mice. C57BL/6 as well as LDL-receptor deficient mice were immunized with heat shock protein 65. LDL-RD and apolipoprotein E knockout (apoE KO) mice were immunized with human B-glycoprotein I. ApoE KO mice were immunized with oxidized LDL. In all immunized mice, a sustained humoral response to the provided antigen was elicited evident by high titers of antibodies by ELISA. A primary cellular immune response was also shown by thymidine incorporation studies employing the antigens in vitro. Immunization with hsp-65 and with beta 2-GPI served to enhance the progression atherosclerosis and led to an increase in the infiltration of CD3 in the subendothelial regions of the early plaques. Transfer of hsp-65 and beta 2-GPI reactive lymphocytes to syngenic mice led to enhancement of fatty streak formation. However, immunization with homologous oxLDL in apoE KO mice led to attenuation of lesion progression concomitant with the production of anti-oxLDL antibodies. Thus, autoimmune factors appear to influence early artherosclerosis progression in mice. If proven in humans these antigen specific responses may be harnessed for selective immunomodulation of the atherosclerotic plaque.
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PMID:Heat shock protein 60/65, beta 2-glycoprotein I and oxidized LDL as players in murine atherosclerosis. 1096 9

Appreciation of the multifactorial nature of atherosclerosis requires a broad understanding of the mechanisms that underlie its pathogenesis. Autoimmune factors have recently been shown to be associated with the initiation and progression of atherosclerosis. In this context, modified lipoproteins were explored because of their de-novo occurrence within the vessel wall, and heat shock proteins are also being reported by several authors as triggers of autoimmune-like reactions that associate with atherosclerosis. Antiphospholipid antibodies in general and anti-beta2-glycoprotein I (beta2GPI) antibodies in particular have been shown to confer a procoagulant tendency in humans, either in the presence or the absence of the antiphospholipid syndrome. These findings and the ability of antibodies to beta2GPI to activate monocytes and endothelial cells led us to consider whether they are proatherogenic. In a series of studies it was shown that inducing an immune response to beta2GPI in atherosclerosis-prone mice accelerated atherosclerosis. We also demonstrated the abundance of beta2GPI in the atheroma, in conjunction with immunopotent cells. Moreover, when beta2GPI-reactive lymph node and spleen cells were transferred to LDL-receptor-deficient mice they promoted fatty streak formation, proving a direct proatherogenic role for beta2GPI-specific lymphocytes. Perhaps the most important implications of the existence of antigen-specific immune reactions within the atheroma is the ability to exploit them for the purpose of selective immunomodulation. Indeed, we have found that inducing immunological tolerance to beta2GPI by prior oral feeding with the antigen resulted in a significant reduction in the extent of atherosclerotic lesions. Thus, beta2GPI is a candidate player in the atherosclerotic plaque, and can possibly be employed as an immunomodulator of plaque progression.
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PMID:Beta2-glycoprotein I and atherosclerosis. 1156 Nov 74

The role of the immune system in modulating atherosclerosis has recently been well documented. Studies have revealed that cellular and humoral immunity plays crucial roles in atherogenic plaque formation. This includes macrophages, CD4+ T cells and dendritic cells as well as autoantigens such as oxidized low density lipoprotein (oxLDL), heat shock proteins and beta2-glycoprotein I. Given these recent advances, various modifications of the immune system in experimental models have been proposed as therapeutic strategies, with the potential of inhibiting atherosclerosis progression. These modifications are switching the immune system (CD4+ T cells) from Th1 towards a Th2 anti-inflammatory cytokine secretion, and the induction of protective antibodies both of which may be induced by specific vaccination. Recent identification of specific immunoreactive antigenic epitopes on modified LDL, their successful implementation for immunization and the induction of atheroprotection, supports the idea that active vaccination may emerge as a novel immuno-modulating atheroprotective strategy.
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PMID:Predictive and protective autoimmunity in cardiovascular diseases: is vaccination therapy a reality? 1621 63

Systemic autoimmune diseases, which comprise a family of conditions which share common pathogenetic mechanisms, are frequently associated to cardiac involvement and to a high prevalence of ischemic coronary events often occurring at a younger age than in normal population. A large increase in mortality is related to premature atherosclerosis with coronary artery disease and stroke in patients with connective tissue diseases. Coronary heart disease is responsible for 40-50% of the death of patients with rheumatoid arthritis. Moreover, a growing body of evidence supports the view that autoimmune mechanisms are involved in the pathogenesis of cardiovascular disease. Inflammatory heart disease is a rising concern worldwide. Similar mechanisms link autoimmune diseases, including the association of increased disease with proinflammatory cytokines and the importance of regulatory mechanisms in the control of chronic inflammation. The role of the immune system in modulating atherosclerosis has recently been well documented. Studies have revealed that cellular and humoral immunity plays crucial roles in atherogenic plaque formation. This includes macrophages, CD4+ T cells and dendritic cells as well as autoantigens such as oxidized low-density lipoprotein (oxLDL), heat shock proteins and beta2-glycoprotein I. The inflammatory component is not localized to the "culprit" plaque, but it is diffused to the entire coronary vascular bed, and involves also the myocardium. The aim of the conference (2nd conference on heart, rheumatism and autoimmunity) was to focus the attention of the participants on some pathogenetic, clinical and therapeutic aspects at the boundary between cardiology and rheumatology and to encourage the debate among clinicians and basic researchers with different backgrounds and experiences.
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PMID:2nd conference on heart, rheumatism and autoimmunity, Pescara, Italy, May 19-20, 2005. 1633 12

Antiphospholipid syndrome is characterized by arterial or venous thrombosis, and the presence of antiphospholipid antibodies (aPL). APL are considered to be a cause of an acquired hypercoagulable state leading to stroke and transient ischemic attack (TIA). We examined the causes in 50 young patients with ischemic stroke. The most prevalent cause was atherosclerosis and the incidence of APS was 12.5%. APL comprise a heterogeneous group of autoantibodies, such as beta2-glycoprotein I dependent anticardiolipin antibody (beta2-GPIaCL), lupus anticoagulant (LA), and other antiphospholid-protein antibodies. We examined the incidence and the pathogenic role of antiphospholipid protein antibodies. The subjects comprised 250 patients (155 male, 95 females) with ischemic stroke, aged 26 to 92 years (mean 72 years). We measured beta2-GPI aCL, IgG aCL, LA, phosphatidyserine dependent antiprothrtombin antibody (PS-PT), antiphosphatidyl-serine antibody (PS), antiphosphatidyl-inositol antibody (PI) in each patient. The incidence of beta2-GPI aCL, IgG aCL, LA, phosphatidyserine, PS-PT, PS, and PI was 2.8%, 12%, 9.2%, 7.2%, 9.6%, and 8.8%, respectively. The incidence of young stroke patients under 50 years was 5.2%. Among 13 young stroke patients, 5 had SLE. Among 23 patients with LA., 18 (78%) patients had PS-PT. Anti-PS-PT antibody is closely related to LA. Antinuclear antibody was detected in 79% of the patients with aPS and/or aPI. We compared the carotid ultrasonographic findings in positive aPI or aPS patients with those in negative ones. Increased IMT, plaque score and carotid stenosis were more common in aPI and aPS-positive patients than in negative ones Three of 5 patients who showed positive beta2-GPI, aCL and LA, simulataneously, had sysyemic lupus erythematosus as an immulological background. Two of 3 patients with PI and/or PS and beta2-GPI and/or LA were patients with SLE. Antiphospholipid antibody was considered to be a risk factor of stroke, especially in SLE and/or young female patients. The incidence of lupus anticoagulant is more common than beta2-GPI aCL in ischemic stroke. In SLE patients with stroke, multi-antiphospholipid-protein antibodies was inclined to be present. LA is closely related to ant-PS-PT and aPI and aPS are associated with anti-nuclear antibody and precipitation of atherosclerosis.
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PMID:[Antiphospholipid syndrome and stroke]. 1644 44

Ever increasing evidence supports the association between psoriasis and cardiovascular risk. Antiphospholipid antibodies (APAs), which can occur in many autoimmune diseases, are considered prothrombotic and have been associated with atherosclerosis. The aim of this study is to evaluate the prevalence and levels of APAs in psoriasis patients. Fifty patients with moderate to severe plaque psoriasis and 48 healthy subjects were investigated for lupus anticoagulant (LAC) by screening and confirmatory coagulation tests, as well as for antibodies against cardiolipin or beta2-glycoprotein I. Levels of APAs and LAC-related parameters were similar for patients with psoriasis and normal controls (p>0.05). APAs were found in only one psoriatic patient (2%) and in none of the controls. LAC was detected in 2 patients (4%) and in one subject of the control group (2.1%). These results suggest that the prevalence of APAs is not increased in plaque psoriasis as compared to the control group. The increased cardiovascular risk observed in psoriatic patients is therefore likely to be correlated to factors different from APAs.
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PMID:Is there an association between antiphospholipid antibodies and psoriasis? 1884 75


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