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)

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.
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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

Antiphospholipid antibodies (aPL) generated in experimental animals cross-react with ATP. We therefore examined the possibility that aPL IgG from human subjects bind to ATP by affinity column and an enzyme linked immunosorbent assay (ELISA). Sera with high levels of aPL IgG were collected from 12 patients with the antiphospholipid syndrome (APS). IgG fractions from 10 of 12 APS patients contained aPL that could be affinity-bound to an ATP column and completely eluted with NaCl 0.5 M. A significant (> 50%) inhibition of aPL IgG binding by ATP 5 mM was found in the majority. Similar inhibition was obtained with ADP but not with AMP or cAMP. All the affinity purified anti-ATP antibodies also bound beta2-glycoprotein-I (beta2-GPI, also known as apolipoprotein H) suggesting that, similar to most pathogenic aPL, their binding depends on this serum cofactor. We further investigated this possibility and found that the binding of beta2-GPI to the ATP column was similar to that of aPL IgG in that most was reversed by NaCl 0.5 M. Furthermore, addition of beta2-GPI to aPL IgG significantly increased the amount of aPL binding to an ATP column. We conclude that aPL IgG bind ATP, probably through beta32-GPI. This binding could interfere with the normal extracellular function of ATP and similar neurotransmitters.
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PMID:Antiphospholipid antibodies bind ATP: a putative mechanism for the pathogenesis of neuronal dysfunction. 1629 22

Whereas antiphospholipid antibodies (aPL) are associated with thrombotic events and recurrent spontaneous abortion (RSA), the contribution of anti-beta2 glycoprotein 1 (beta2GP1) and anti-annexin V antibodies as risk factors for RSA remain poorly understood. We investigated anti-beta2-GPI and anti-annexin V IgM and IgG antibodies as potential risk factors for RSA in 200 women with more than three consecutive idiopathic RSA, and 200 age-matched, healthy, parous women. Pearson's chi squared test analysis showed that while anti-beta2-GPI IgG (P = 0.416) and IgM (P = 0.72) were comparable between patients and controls, elevated anti-annexin V IgG (P = 0.006), but not IgM (P = 0.084), was more pronounced in patients. Higher frequencies of elevated IgG-only (P = 0.005), but not IgM-only (P = 1.000; OR = 6.66), anti-annexin V antibodies were noted among patients. Multinomial regression analysis showed that body-mass index (overweight and obesity; P = 0.008), education status (P < 0.001) and anti-beta2-GPI IgM (P = 0.033), but not IgG (P = 0.723), were associated with early abortion, while anti-beta2-GPI IgG (P = 0.030) and anti-annexin V IgG (P = 0.004) were associated with late RSA. For combined early-late RSA, the only variable selected was education status (P < 0.001), and neither anti-annexin V nor anti-beta2-GPI IgM and IgG was associated with early-late RSA. Accordingly, anti-annexin V and anti-beta2-GPI should be regarded as independent risk markers of RSA.
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PMID:A case-control study on the association of idiopathic recurrent pregnancy loss with autoantibodies against beta2-glycoprotein I and annexin V. 1659 32

Peripheral artery disease (PAD) is mostly related to atherosclerosis. Autoimmunity and, in particular, antibodies to cardiolipin (aCL) and phospholipid cofactors such as beta2-glycoprotein I (beta2-gpI) might influence the development of atheroma. Beta2-glycoprotein I (beta2-gpI) has been found in atheroma. It has previously been shown that immunoglobulin A (IgA) anti-beta2-gpI antibodies are associated with a risk of cerebral ischemia and myocardial infarction. This case control study aimed to determine whether elevated levels of aCL/anti-beta2-gpI antibodies are associated with a risk of symptomatic PAD (sPAD). Cases comprised a nonselected population of patients with sPAD (intermittent claudication or critical ischemia). Patient recruitment was based on arteriography changes. Controls were selected from patients admitted to orthopedic wards as a result of fractures or muscle-ligamentous disorders. Age, sex, race, hypertension, smoking, diabetes mellitus, and hypercholesterolemia were evaluated as risk factors in both groups. IgG/IgM/IgA aCL and anti-beta2-gpI were detected by enzyme-linked immunoabsorbant assays (ELISA). To estimate the grade of association of antibodies with sPAD, odds ratios (OR) were calculated. Logistic regression was utilized for adjustment of confounding factors. Seventy-seven cases and 93 controls were studied. The mean age was 61.5 years for cases and 47.5 years for controls (p <0.001). Among the risk factors evaluated, the presence of hypertension showed the strongest association with sPAD (OR 12.1; 95%CI 5.8-30). The presence of IgA anti-beta2-gpI was independently associated with sPAD (OR 5.4; 95%CI 1.8-15.8; p = 0.01). IgA aCL was strongly associated with the outcome (nonadjusted OR 11.5 after Agresti correction). IgA aCL and IgA anti-beta2-gpI antibodies were not associated with any known risk factors for sPAD or with arteriography changes. The occurrence of these autoantibodies might represent one of the links between autoimmunity and atherosclerosis in patients with sPAD.
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PMID:Autoantibodies to the atheroma component beta2-glycoprotein I and risk of symptomatic peripheral artery disease. 1762 83

Beta(2)-glycoprotein-I (beta(2)-GPI, also known as apolipoprotein H) is a major autoantigen in the antiphospholipid syndrome (APS), a disease commonly affecting the central nervous system. We examined whether beta2-GPI and similar proteins exist in rat and human brains. No expression was found on Northern blot analysis of human brain. Utilizing a standard procedure for the isolation of serum beta2-GPI we purified a 100 kD human brain protein, which was found by peptide sequencing to have full homology with the serum protein, histidine-rich glycoprotein (HRGP). Expression of HRGP in rat and human brain was established by RT-PCR studies and a partial sequence of rat brain HRGP was obtained showing 68% homology with the human protein. IgG from most APS patients bound to HRGP, which shares distinct biochemical properties with beta2-GPI, is present in the brain and may be an important autoantigen.
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PMID:Identification of histidine-rich glycoprotein, a potential autoantigen, in human and rat brain preparations. 1778 36

Apolipoprotein H (apoH, also named beta-2 glycoprotein I) is found on several classes of lipoproteins, and is involved in the activation of lipoprotein lipase in lipid metabolism. We have comprehensively investigated the association of variation in the apoH gene (APOH) with lipid traits in hepatic cholesterol transport, dietary cholesterol transport (DCT), and reverse cholesterol transport (RCT). Our study population consisted of families from the Genetic Epidemiology Network of Arteriopathy multicenter study that include African Americans, Mexican Americans, and European Americans. We individually tested 36 single-nucleotide polymorphisms (SNPs) that span the APOH locus, including nonsynonymous variants that result in known apoH charge isoforms. In addition, we constructed haplotypes from SNPs in the 5' promoter region that comprise cis-acting regulatory elements, as well as haplotypes for multiple amino acid substitutions. We found point-wise significant associations of APOH variants with various lipid measures in the three racial groups. The strongest associations were found for DCT traits (triglyceride and apoE levels) in Mexican Americans with a nonsynonymous variant (SNP 14917, Cys306Gly) that may alter apoH protein folding in a region involved in phospholipid binding. In conclusion, family-based analyses of APOH variants have identified associations with measures of lipid metabolism in three American racial groups.
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PMID:Comprehensive evaluation of apolipoprotein H gene (APOH) variation identifies novel associations with measures of lipid metabolism in GENOA. 1867 59

The objective of our study was to evaluate the significance of extended antiphospholipid profile in patients with venous thromboembolism without any systemic autoimmune disease. In 140 patients (age 18-69 years; 47.1% men) with venous thromboembolism and 136 control participants we tested anticardiolipin antibodies, anti-beta 2 glycoprotein I (anti-beta2-GPI) and also non-criteria antiphospholipid antibodies: antiphosphatidic acid, antiphosphatidylethanolamine, antiphosphatidylglycerol, antiphosphatidylinositol, antiphosphatidylserine. Commercial and in-house enzyme-linked immunosorbent assays were used. The antibodies with significantly higher prevalence in patients (compared to controls) were: immunoglobulin (Ig) M-anticardiolipin antibodies (12.9%; P = 0.035), IgG-anti-beta2-GPI (16.4%; P = 0.0032), IgM-antiphosphatidylethanolamine (14.3%; P = 0.014). In most cases, these three antibodies did not overlap. In conclusion, of non-criteria antiphospholipid antibodies, only antiphosphatidylethanolamine were significantly more prevalent in patients with venous thromboembolism, with only minor overlapping with the criteria antiphospholipid antibodies. Our results suggest the possible utility of searching for antiphosphatidylethanolamine in the clinical suspicion of antiphospholipid syndrome and the absence of criteria antiphospholipid antibodies.
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PMID:Laboratory evaluation of antiphospholipid antibodies in patients with venous thromboembolism. 1922 Nov

A debate on updating the laboratory criteria of antiphospholipid syndrome (APS) was recently opened in view to lower the risk of over diagnosis of the syndrome. Based on data related to thrombotic APS, it proposes the exclusion of anticardiolipin antibodies (aCL) and anti-beta2-glycoprotein 1 (a-beta2-GPI) IgM detection. Here, we examine this possibility in a study which focuses on obstetrical APS (OAPS). We report new data on a prospective multicenter European cohort of 109 pregnant women having APS. Among them, 73 had purely obstetrical APS, not associated to autoimmune diseases or thrombosis. Isolated antibodies and isolated aCL positivity were present in 50/109 (46%) and in 34/109 (31%) of the women, respectively. An isolated a-beta2-GPI IgM was present in three women. These results suggest that aCL and a-beta2-GPI IgM cannot be dropped for the diagnosis and classification of OAPS. The low level of some antibodies associated with severe obstetrical complications raise the issue of keeping or not the same laboratory criteria for OAPS and for thrombotic APS and whether additional criteria after large prospective studies could further improve diagnosis.
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PMID:Laboratory criteria of the obstetrical antiphospholipid syndrome. Data from a multicentric prospective European women cohort. 1957 63

A 45 year old male was admitted to the hospital for unsteady gait and dizziness. The brain CT showed bilateral cerebellar ischemic stroke. The MRI corroborated the stroke in the cerebellum with a third acute ischemic stroke in the pons. The laboratory work up showed a positive anti beta2-glycoprotein I antibodies. The cerebral angiogram showed the territories occluded and also a rare malformation of the cranium vertebral junction called assimilation of the atlas. We concluded that due to the turbulence created in the V3 segment of the vertebral artery surrounding the atlas, the presence of the anti beta2-glycoprotein was the cause of the infarction in this patient.
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PMID:[A dangerous combination for stroke in young patient: assimilation of the atlas and anti beta2-glycoprotein I antibodies]. 1962 73

In this study we evaluated the diagnostic accuracy for antiphospholipid syndrome (APS) of new fully automated immunoassays for anticardiolipin (aCL) and anti-beta2 glycoprotein I (anti-beta2-GPI) auto-antibody detection (EliA-Phadia), and compared the results with those obtained with Orgentec and Inova ELISA methods. Sixty-two APS patients and 123 controls (20 syphilis, 33 Lyme disease, 30 HCV infection and cryoglobulinemia, 40 healthy subjects) were studied. Using the 99(th) percentile cutoff, the sensitivity and specificity of EliA aCL IgG, aCL IgM, anti-beta2-GPI IgG, and anti-beta2-GPI IgM were 69.4% and 81.9%, 64.5% and 86.7%, 64.5% and 98.8%, and 53.2% and 92.8%, respectively. Using the Sydney criteria cutoff (>40 GPL/MPL units), sensitivity and specificity of EliA aCL IgG and aCL IgM were 45.2% and 98.8%, and 35.5% and 97.5%, respectively. The best diagnostic efficiency was obtained combining the aCL tests (>40 GPL/MPL units) with the anti-beta2-GPI tests (sensitivity 85.7%, specificity 90.4%). The area under the ROC curves for EliA, Orgentec, and Inova methods were 0.870, 0.940, and 0.850 for aCL IgG; 0.820, 0.820, and 0.820 for aCL IgM; 0.910, 0.960, and 0.920 for anti-beta2-GPI IgG; 0.840, 0.840, and 0.820 for anti-beta2-GPI IgM, respectively. Finally, the overall agreement between EliA assays and the other two ELISA methods ranged from moderate (anti-beta2-GPI IgG EliA versus Orgentec: Cohen's k = 0.426) to good (anti-beta2-GPI IgM EliA vs. Inova: k = 0.841). In conclusion, newly developed EliA methods for antiphospholipid antibody detection perform similarly to other ELISA assays and represent a useful tool for APS laboratory diagnosis in daily practice.
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PMID:Accuracy of the first fully automated method for anti-cardiolipin and anti-beta2 glycoprotein I antibody detection for the diagnosis of antiphospholipid syndrome. 1975 27


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