Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P02749 (
beta2-glycoprotein I
)
836
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Human
apolipoprotein H
(
ApoH
), also called
beta 2-glycoprotein I
, is a 50-kDa serum glycoprotein whose function is not clearly defined. We have cloned and sequenced
ApoH
cDNAs both from human liver and from a human hepatoma cell line (HepG2). Both cDNA sequences predict a protein 345 amino acids (aa) in length. This sequence includes a 19-aa hydrophobic, N-terminal signal sequence which is not present in the mature protein [Lozier et al., Proc. Natl. Acad. Sci. USA 81 (1984) 3640-3644]. It differs from this previously reported aa sequence at two positions, both of which strengthen the conservation among the four short consensus repeats within the
ApoH
molecule. COS-1 cells transiently transfected with the
ApoH
cDNA in a eukaryotic expression vector produced a single species of
ApoH
mRNA and secreted in the
ApoH
protein. The level of
ApoH
mRNA expressed by HepG2 cells is downregulated by incubation with inflammatory mediators, implying that
ApoH
is a negative acute-phase protein.
Gene 1991
Dec
15
PMID:Nucleotide sequence and expression of the human gene encoding apolipoprotein H (beta 2-glycoprotein I). 174 14
Human
beta 2-glycoprotein I
(
beta 2-GPI
) is involved in cardiolipin (CL) binding of anticardiolipin antibodies (aCL) in systemic lupus erythematosus (SLE). We examined the inter-species differences of
beta 2-GPI
in alternation of CL binding of aCL.
beta 2-GPI
preparations were obtained from human, bovine, and rat sera by sequential CL--polyacrylamide affinity, DEAE--cellulose, and anti-human IgG-conjugated Sepharose CL-4B column chromatography, and they had apparent molecular weights of 50, 53, and 55 kDa respectively. Human
beta 2-GPI
not only enhanced CL binding by aCL in SLE but also depressed it by those in syphilis. Either bovine and rat
beta 2-GPI
exerted no or quite small inhibition of the binding of syphilitic aCL compared with human
beta 2-GPI
whereas all three species of
beta 2-GPI
generated binding of aCL in SLE to a similar degree. Further, a complete cDNA clone, p
beta 2-GPI
, was isolated from a human hepatoma cell line, HepG2, and its nucleotide sequence was analyzed. The sequences of bovine and rat counterpart molecules (
beta 2-GPI
) are highly homologous to that of the deduced sequence, and their corresponding regions are 84.0 and 82.5% identical to the complete domain and to the amino acid sequence 53-326 of human
beta 2-GPI
respectively. One of major differences appears at position 154 in human
beta 2-GPI
, and might be associated with the inhibitory effect on the binding of syphilitic aCL. The sequencing analysis of these
beta 2-GPI
proteins might provide leads to functional sites of domains which would be associated with such serological phenomena.
Int Immunol 1991
Dec
PMID:Molecular definition of human beta 2-glycoprotein I (beta 2-GPI) by cDNA cloning and inter-species differences of beta 2-GPI in alternation of anticardiolipin binding. 177 18
The effect of sera and purified IgG isolated from plasma of 46 patients with systemic lupus erythematosus (SLE) and 9 healthy donors on the endothelial cell (EC) mediated protein C activation was investigated. Out of the 46 SLE sera used, 19 were antiphospholipid antibodies (aPL) positive. From 12 patients IgG was isolated, of which 6 contained aPL. EC were first incubated with IgG (7 mg/ml) or serum (1:1 diluted) for 1 h and then tested for their ability to promote protein C activation by thrombin, with the cells either in a monolayer or in a suspension. The normal range (mean of control values +/- 2 SD) of protein C activation was 80-120%. In contrast to others, we could not detect an inhibition of protein C activation by any of the patient IgG's or sera. The recently described cofactor for binding of antiphospholipid antibodies to phospholipids,
beta 2-glycoprotein I
, was purified and added to the purified IgG's. A combination of these two components did not inhibit the EC mediated protein C activation by thrombin. This study suggests that the inhibition of the protein C activation, mediated by EC, is not a general mechanism by which aPL related thrombosis can be explained.
Thromb Haemost 1991
Dec
02
PMID:In vitro studies of antiphospholipid antibodies and its cofactor, beta 2-glycoprotein I, show negligible effects on endothelial cell mediated protein C activation. 179 12
We determined plasma
apolipoprotein H
(
beta 2-glycoprotein I
) levels in 300 healthy adult individuals and evaluated the frequencies of the BgN and BgD alleles in a Japanese population. These results were then compared with the previous reports. The plasma apo H levels in the subjects showed bimodal distribution: 274 subjects were in the range 15.6-33.2 mg/dl and were considered to be homozygous for BgN (phenotype NN), and 26 subjects were found in the range 9.6-14.8 mg/dl and were presumably heterozygous for BgN and BgD (phenotype ND). In this study, no sample below 5 mg/dl (phenotype DD) was found. Mean plasma apo H levels in NN and ND groups were 22.1 +/- 1.6 mg/dl and 12.5 +/- 1.6 mg/dl, respectively. The gene frequencies of BgN and BgD in a Japanese population were 0.957 and 0.043, respectively. These results were similar to gene frequencies of BgN and BgD in Caucasoids.
Jinrui Idengaku Zasshi 1989
Dec
PMID:Plasma apolipoprotein H (beta 2-glycoprotein I) phenotype frequencies in a Japanese population. 263 88
The combination of gel permeation chromatography and high-performance liquid chromatography proves to be very effective for the purification of high-molecular-weight glycopeptides containing a single glycan, that have been difficult to separate by other procedures. In order to facilitate comparison of the chromatographic properties of glycopeptides derived from a variety of proteins and having different structures, identical procedures were used for their purification. The method was applied to a series of human plasma proteins, including immunoglobulin D, ceruloplasmin, hemopexin,
beta-2-glycoprotein I
, 3.1S alpha-2-leucine-rich glycoprotein, and alpha-1-B-glycoprotein. All the purified glycopeptides were placed in the protein structure of these plasma proteins. In several cases the carbohydrate structure has been determined by collaborating groups. Immunoglobulin D is the first example of a glycoprotein whose entire primary structure has been defined by utilizing a a single protein source. Furthermore, hemopexin and 3.1S alpha-2-leucine-rich glycoprotein were both found to contain GalN oligosaccharide, which had not previously been identified in these proteins. The method was also used to identify the oligosaccharide that is missing in a carbohydrate variant of ceruloplasmin.
J Chromatogr 1984
Dec
28
PMID:Purification of glycopeptides of human plasma proteins by high-performance liquid chromatography. 653 Apr 29
We have previously demonstrated that patients with cirrhosis may be positive for lupus anticoagulant and anticardiolipin antibodies. The prevalence and clinical value of antiphospholipid antibodies in cirrhosis have never been described. Besides, it has not yet been determined if serum levels of
beta-2-glycoprotein I
, which is synthesized by the liver and mediates the interaction between cardiolipin and anticardiolipin antibodies affects lupus anticoagulant detectability in cirrhosis. We evaluated the prevalence of lupus anticoagulant in 63 patients with cirrhosis and related it to
beta-2-glycoprotein I
serum levels. We also analyzed whether lupus anticoagulant and anticardiolipin antibodies were associated with previous thrombotic complications. Eleven patients (18%) were lupus anticoagulant positive; 14 (22%) had high values of anticardiolipin antibodies. Fourteen patients had a previous history of splanchnic venous thrombosis (n = 9) or thrombophlebitis (n = 5). A significant association between lupus anticoagulant (p = 0.0001), anticardiolipin antibodies (p = 0.0001) and venous thrombosis was found. Patients with severe liver failure had significantly lower
beta-2-glycoprotein I
levels than those with moderate (p < 0.01) or low (p < 0.001) hepatic insufficiency. Among 14 anticardiolipin antibodies positive patients, six with severe liver failure were lupus anticoagulant negative and had
beta-2-glycoprotein I
values below 100 micrograms/ml. In four of these, basal values of dilute activated partial thromboplastin time were not modified by the addition of 50 micrograms/ml of exogenous
beta-2-glycoprotein I
. This study shows that antiphospholipid antibodies are relatively frequent in cirrhosis and that
beta-2-glycoprotein I
levels are not so low as to affect lupus anticoagulant detectability.(ABSTRACT TRUNCATED AT 250 WORDS)
J Hepatol 1994
Dec
PMID:Prevalence of lupus anticoagulant in patients with cirrhosis: relationship with beta-2-glycoprotein I plasma levels. 769 32
We studied the effect of
beta 2-GPI
on binding of antibodies in sera from patients with leprosy and patients with the antiphospholipid syndrome (APS) to CL in enzyme-linked immunosorbent assays (ELISAs). Increased levels of IgG aCL were detected in 59 of 61 leprosy patients' sera by the standard aCL-ELISA in the presence of bovine
beta 2-GPI
and in 60 of the 61 leprosy patients' sera by the modified aCL-ELISA without
beta 2-GPI
. When tested by both aCL-ELISAs on the same plate, 10/31 leprosy sera and 9/10 APS sera bound better in the standard aCL-ELISA, 16/31 leprosy sera bound better in the modified aCL-ELISA and in five leprosy and one APS sera the difference was not significant. A dose-dependent enhancing effect of
beta 2-GPI
on the leprosy and APS sera binding to CL was confirmed using purified human
beta 2-GPI
. Enhanced binding was seen if
beta 2-GPI
was added either before or together with the test serum. In 11/61 leprosy sera increased levels of IgG antibodies against
beta 2-GPI
were found by ELISA. Leprosy anti-
beta 2-GPI
antibodies appear to be a separate antibody population recognizing only
beta 2-GPI
adsorbed on the ELISA plate. These results demonstrate heterogeneity of leprosy aCL with respect to their
beta 2-GPI
requirement for binding to CL.
Lupus 1994
Dec
PMID:Anticardiolipin antibodies in infections are heterogenous in their dependency on beta 2-glycoprotein I: analysis of anticardiolipin antibodies in leprosy. 770 10
We investigated whether or not the use of Tween 20 could help to distinguish
beta 2-glycoprotein I
(GPI) independent anticardiolipin antibody (aCL) (syphilis-type aCL) from GPI-dependent aCL (SLE-type aCL) in a GPI-dependent/independent aCL ELISA. aCL was positive in all 16 SLE patients and all 15 syphilis patients, who were positive for aCL in the standard ELISA, in the GPI-independent ELISA with Tween 20. GPI-dependent aCL was detected in 12/16 SLE patients by the GPI-dependent ELISA with Tween 20. aCL was not detected in any of the syphilis patients by GPI-dependent ELISAs. On the basis of these results, we recommend that Tween 20 should be used in ELISAs to distinguish GPI-dependent aCL from GPI-independent aCL.
Br J Haematol 1993
Dec
PMID:Distinguishing beta 2-glycoprotein I dependent (systemic lupus erythematosus type) and independent (syphilis type) anticardiolipin antibody with Tween 20. 794
We investigated the clinical significance of IgG phospholipid-dependent anti-
beta 2-glycoprotein I
(
beta 2-GPI
) antibodies in patients with SLE. The study population consisted of 140 patients with SLE. Sera were examined for IgG phospholipid-dependent anti-
beta 2-GPI
antibodies by ELISA. IgG phospholipid-dependent anti-
beta 2-GPI
antibodies were detected in 21 of 140 patients (15%) and remained positive from 4 to 98 months. Significantly higher incidences of thrombosis, intrauterine fetal loss, thrombocytopenia, patients with antiphospholipid syndrome (APS), prolonged APTT, BFP-STS and hemolytic anemia were found in SLE patients with phospholipid-dependent anti-
beta 2-GPI
antibodies. Moreover, significantly lower incidences of malar rash and serositis were found in SLE patients with phospholipid-dependent anti-
beta 2-GPI
antibodies, and the majority of these patients satisfied four or five of the revised criteria items of the American Rheumatism Association. These differences were not observed when we compared clinical manifestations in anticardiolipin antibody-positive patients with those in antibody-negative patients by conventional ELISA. These results indicated that SLE patients with IgG phospholipid-dependent anti-
beta 2-GPI
antibodies show an unique form of SLE.
Lupus 1995
Dec
PMID:Clinical significance of phospholipid-dependent anti-beta 2-glycoprotein I (beta 2-GPI) antibodies in systemic lupus erythematosus. 874 70
The binding capacity to cardiolipin and the functional affinity of affinity-purified anticardiolipin (aCL) IgG of patients with autoimmune disease have been compared with those of individuals with malaria and acquired immunodeficiency syndrome (AIDS). The binding of autoimmune IgG aCL was enhanced gradually by the incorporation of increasing amounts of
beta 2-glycoprotein I
(beta 2GPI) into the assay, in contrast to that of patients with infectious diseases. In addition, there were significant reductions of functional affinity in autoimmune disease, but not in malaria or in AIDS. These results indicate that beta 2GPI requirement for binding to the target antigen varies inversely with functional affinity in autoimmune disease when beta 2GPI was present, and suggest that IgG aCL are more heterogeneous in this type of disorder than in patients with infectious disease.
Lupus 1995
Dec
PMID:Role of beta 2-glycoprotein I in the anticardiolipin antibody affinity for phospholipid in autoimmune disease. 874 71
1
2
3
4
5
Next >>