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)

A phage display library made from Staphylococcus aureus DNA was sorted against a central venous catheter (CVC) that had been removed from a patient 2 days after insertion. After the first panning, approximately 50% of the clones encoded proteins known to interact with mammalian proteins. After the second and third pannings, fibrinogen-binding and beta2-glycoprotein I (beta2-GPI)-binding phage particles were clearly dominating. Proteins adsorbed to different CVCs were investigated using specific antibodies. Among the proteins probed for, fibrinogen was most abundant, but, interestingly, beta2-GPI was also detected on all tested CVCs.
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PMID:Sorting a Staphylococcus aureus phage display library against ex vivo biomaterial. 1535 15

Can autoantibodies (Ab's) and cytokines play a role in epilepsy?Monozygotic twins discordant for epilepsy (most probably Rasmussen's encephalitis (RE)), compared to 49 neurologically intact controls, were both found to contain in their serum (at the time of epilepsy diagnosis) significantly elevated levels of specific Ab's against peptide B (amino acids 372-395) of the ionotropic glutamate receptor of AMPA subtype 3 (i.e. GluR3B peptide). Interestingly, both twins also had clinically elevated levels of Ab's to double-stranded (ds) DNA, glutamic acid decarboxylase, nuclear antigens, beta2-glycoprotein I and cardiolipin, as in "classical" autoimmune diseases. Both twins also had significantly elevated levels of IFNgamma, TNFalpha, IL-4 and IL-10 in the serum, compared to the controls. Comparing the twins revealed that the epileptic twin had significantly higher levels of five of the above anti-self Ab's, but significantly lower levels of all four cytokines compared to her healthy sister. Importantly, the epileptic twin, alike three other RE patients tested herein, contained elevated levels of Ab's to GluR3B and dsDNA also in cerebrospinal fluid (CSF) (unavailable of the healthy twin). Our results suggest that the various autoimmune Ab's studied herein, all of which are known already to have a potential to be pathogenic in the nervous system and/or peripheral organs, may play a role in some types of epilepsy. The titer of such Ab's and of key cytokines may be crucial for either facilitating or arresting the development of epilepsy. Our findings also show that anti-GluR3B Ab's in serum are not necessarily detrimental (their presence in the CSF may be more dangerous), and that they are not a mere side effect of already existing epilepsy, as they were found herein in serum of a healthy individual. These findings and suggestions may be of clinical importance and call for further studies.
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PMID:Monozygotic twins discordant for epilepsy differ in the levels of potentially pathogenic autoantibodies and cytokines. 1604 Mar 34

Apolipoprotein H (APOH), also known as beta2-glycoprotein I, is a major antigen for the production of antiphospholipid antibodies in autoimmune diseases. Previously we have examined DNA variation in the coding region of the APOH gene and determined the molecular basis of the common protein polymorphism. Here we report the results of DNA sequence variation in the entire APOH gene encompassing a 20.3 kb region in 46 Caucasian Americans and 48 African American chromosomes. A total of 150 single nucleotide polymorphisms (SNPs) and one tri-allelic polymorphism were identified, including 8 in the coding region, 14 in the 5'-region and 2 in the 3'- region; the remainder were observed in introns. The observed number of SNPs was higher in the African American sample than in the Caucasian sample (130 vs. 84). We examined the race-specific linkage disequilibrium pattern among SNPs and identified maximally informative SNPs for future association studies. Altogether, we have identified 17 informative SNPs among Caucasians and 35 in blacks. The discovery of a full range of sequence variation and identification of race-specific informative SNPs in the APOH gene may facilitate the rapid evaluation of this variation in relation to autoimmune diseases.
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PMID:Complete DNA sequence variation in the apolipoprotein H (beta-glycoprotein I) gene and identification of informative SNPs. 1644 Dec 53

Proliferating cells have a higher metabolic rate than quiescent cells. To investigate the role of metabolism in cell cycle progression, we examined cell size, mitochondrial mass, and reactive oxygen species (ROS) levels in highly synchronized cell populations progressing from early G1 to S phase. We found that ROS steadily increased, compared to cell size and mitochondrial mass, through the cell cycle. Since ROS has been shown to influence cell proliferation and transformation, we hypothesized that ROS could contribute to cell cycle progression. Antioxidant treatment of cells induced a late-G1-phase cell cycle arrest characterized by continued cellular growth, active cyclin D-Cdk4/6 and active cyclin E-Cdk2 kinases, and inactive hyperphosphorylated pRb. However, antioxidant-treated cells failed to accumulate cyclin A protein, a requisite step for initiation of DNA synthesis. Further examination revealed that cyclin A continued to be ubiquitinated by the anaphase promoting complex (APC) and to be degraded by the proteasome. This antioxidant arrest could be rescued by overexpression of Emi1, an APC inhibitor. These observations reveal an intrinsic late-G1-phase checkpoint, after transition across the growth factor-dependent G1 restriction point, that links increased steady-state levels of endogenous ROS and cell cycle progression through continued activity of APC in association with Cdh1.
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PMID:Regulation of late G1/S phase transition and APC Cdh1 by reactive oxygen species. 1673 33

In order to elucidate beta2-GPI at the DNA level and characterize its polymorphisms, mRNA expression, protein levels and clinical significance at each of these steps, a molecular review of beta2-GPI literature was performed. The human beta2-GPI complete nucleotide sequence has been reported and it consists of 8 exons separated by large introns. The beta2-GPI gene is polymorphic with four alleles. The distribution of point mutations can be significantly different between various racial populations. DNA variation studies of the beta2-GPI gene identified a total of 151 single-nucleotide polymorphisms, 26 of which are within regions with potential clinical significance. Southern blot analysis indicated the presence of one gene product only. An atypical TATA box and a hepatic nuclear factor-1 element are both essential for beta2-GPI promoter activity. Transcription factor binding sites for STAT, CREB, C/EBPbeta, NF-1, AP-1, NFAT, HNF-3beta and HNF-1 have been identified in the promoter region of the beta2-GPI gene by computer analysis. The beta2-GPI transcriptional signal of 1.5 kb was detected in Northern blot analysis and its 326-amino-acid sequence was found to be one of the most proline-rich eukaryotic proteins. Amino acid substitutions have been shown to be associated with loss of phospholipid binding, development and recognition of antiphospholipid antibodies.
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PMID:Beta2-glycoprotein I and its clinical significance: from gene sequence to protein levels. 1785 47

Haematological abnormalities are common in systemic lupus erythematosus (SLE). In some cases of acquired von Willebrand syndrome (AvWS), von Willebrand disease (vWD) is associated with autoimmune or lymphoproliferative disorders. In this study, we describe a 36-year-old woman with SLE and AvWS. The patient was referred to our hospital because of easy bruisability and recurrent vaginal bleeding. She had no history of bleeding tendency and no family history of bleeding diathesis, but she had a history of recurrent arthralgia, photosensitivity and sicca symptoms. Tests for antinuclear, anti-double stranded DNA, anticardiolipin and anti-beta2-glycoprotein I antibodies were all positive. Analysis of haemostatic parameters showed complete absence of von Willebrand factor ristocetin cofactor (vWF:Rco), von Willebrand antigen (vWF:Ag) and ristocetin-induced platelet aggregation (RIPA). Electrophoretic analysis of plasma showed a complete absence of high-molecular weight vWF multimer. The presence of antibody to vWF was detected by enzyme linked immunosorbent assay (ELISA). Treatment with corticosteroids improved SLE symptoms and corrected bleeding diasthesis. Also, the multimeric patterns of vWF became normalised and anti-vWF antibody disappeared. These findings indicated that this patient had SLE associated with AvWS, which was ameliorated by corticosteroid treatment.
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PMID:Systemic lupus erythematosus complicated by acquired von Willebrand's syndrome. 1875 68

This study characterized the human apolipoprotein H [APOH; beta(2)-glycoprotein I (beta(2)GPI)] promoter and its variants by in vitro functional experiments and investigated their relationship with human plasma beta(2)GPI levels. We examined the individual effects of 12 APOH promoter single nucleotide polymorphisms in the 5' flanking region of APOH (approximately 1.4 kb) on luciferase activity in COS-1 cells and HepG2 cells and their impact on plasma beta(2)GPI levels in 799 American White people, the DNA binding properties of the APOH promoter using an electrophoretic mobility shift assay in HepG2 cells, the effects of serial deletion analysis of the APOH 5' flanking region in COS-1 and HepG2 cells and cross-species conservation of the APOH promoter sequence. The variant alleles of three single nucleotide polymorphisms (-1219G>A, -643T>C and -32C>A) showed significantly lower luciferase expression (51, 40 and 37%, respectively) as compared with the wild-type allele. The electrophoretic mobility shift assay demonstrated that these three variants specifically bind with protein(s) from HepG2 cell nuclear extracts. Three-site haplotype analysis (-1219G>A, -643T>C and -32C>A) revealed one haplotype carrying -32A (allele frequency = 0.075) to be significantly associated with decreased plasma beta(2)GPI levels (P < 0.001). Deletion analysis localized the core APOH promoter to approximately 160 bp upstream of ATG codon with the presence of critical cis-acting elements between -166 and -65. Cross-species conservation analysis of the APOH promoters of seven species indicated that basic promoter elements are highly conserved across species. In conclusion, we have characterized the functional promoter of APOH and identified functional variants that affect the transcriptional activity of the APOH promoter.
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PMID:Functional and genetic characterization of the promoter region of apolipoprotein H (beta2-glycoprotein I). 2008 41

Human parvovirus B19 (B19V) from the erythrovirus genus is known to be a pathogenic virus in humans. Prevalence of B19V infection has been reported worldwide in all seasons, with a high incidence in the spring. B19V is responsible for erythema infectiosum (fifth disease) commonly seen in children. Its other clinical presentations include arthralgia, arthritis, transient aplastic crisis, chronic anemia, congenital anemia, and hydrops fetalis. In addition, B19V infection has been reported to trigger autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. However, the mechanisms of B19V participation in autoimmunity are not fully understood. B19V induced chronic disease and persistent infection suggests B19V can serve as a model for viral host interactions and the role of viruses in the pathogenesis of autoimmune diseases. Here we investigate the involvement of B19V in the breakdown of immune tolerance. Previously, we demonstrated that the non-structural protein 1 (NS 1) of B19V induces apoptosis in non-permissive cells lines and that this protein can cleave host DNA as well as form NS1-DNA adducts. Here we provide evidence that through programmed cell death, apoptotic bodies (ApoBods) are generated by B19V NS1 expression in a non-permissive cell line. Characterization of purified ApoBods identified potential self-antigens within them. In particular, signature self-antigens such as Smith, ApoH, DNA, histone H4 and phosphatidylserine associated with autoimmunity were present in these ApoBods. In addition, when purified ApoBods were introduced to differentiated macrophages, recognition, engulfment and uptake occurred. This suggests that B19V can produce a source of self-antigens for immune cell processing. The results support our hypothesis that B19V NS1-DNA adducts, and nucleosomal and lysosomal antigens present in ApoBods created in non-permissive cell lines, are a source of self-antigens.
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PMID:Human parvovirus B19 induced apoptotic bodies contain altered self-antigens that are phagocytosed by antigen presenting cells. 2377 9

The complicated clinical picture and biomolecular pattern of human autoimmune diseases (ADs) make knowledge on their etiology still fragmentary. The diagnostic approaches for ADs require improvement both for clinical and research effort to progress. Synthetic biomolecular antigens find growing applications for diagnosis and investigation of ADs. The main goal of this work is to detect interaction between synthetic antigens and autoantibodies in systemic lupus erythematosus within a combined, high-throughput assay. A panel of synthetic antigens has been prepared from DNA, RNA, locked nucleic acids and apolipoprotein H. The binding of synthetic antigens to autoantibodies has been confirmed in sera samples from those with active systemic lupus erythematosus (SLE) by indirect enzyme linked immunosorbent assay. Our study provides an efficient methodology for combined autoantibody profiling in SLE.
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PMID:Combined Assay for Detecting Autoantibodies to Nucleic Acids and Apolipoprotein H in Patients with Systemic Lupus Erythematosus. 3166 63


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