Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lupus anticoagulants, commonly found in the immunoglobulin fraction of patients with the antiphospholipid syndrome (APS), and the normal plasma protein beta 2-glycoprotein 1 (beta 2GP1) may both contribute to the in vitro impairment of prothrombin activation associated with the APS. We examined the effects upon prothrombin activation supported by phospholipid vesicles of plasma IgG preparations from APS patients in the presence and absence of beta 2GP1. Using a purified system for measurement of prothrombin activation to thrombin, we demonstrated significant phospholipid concentration-dependent inhibition of prothrombin activation in the absence of beta 2GP1 by 11 consecutive patient IgG preparations. The degree of inhibition of prothrombin activation by equivalent concentrations of patient IgG correlated well with the extent of prolongation of the plasma clotting time in lupus anticoagulant assays of whole patient plasma. Additional studies with eight patient IgG preparations indicated that the addition of beta 2GP1 to patient IgG-phospholipid vesicle mixtures resulted in either independently additive inhibition by the two protein species (six cases) or potential inhibition of beta 2GP1 of the IgG inhibitory activity demonstrable in the absence of beta 2 GP1 (two cases). In addition, beta 2GP1-independent inhibition of prothrombin activation also occurred with three patient IgG preparations obtained by affinity binding to cardiolipin.
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PMID:Inhibition of prothrombin activation by antiphospholipid antibodies and beta 2-glycoprotein 1. 799 95

The antiphospholipid antibody syndrome consists of a presentation with venous thrombosis, arterial thrombosis (or vasculopathy), recurrent pregnancy loss, or thrombocytopenia, in the setting of high-titer anticardiolipin antibody or lupus anticoagulant. Characteristics of the lupus anticoagulant (an antibody detected by a functional assay) and anticardiolipin antibody are reviewed, in light of new information on the role of plasma proteins, especially B2-glycoprotein I. The advantages and disadvantages of screening and confirmatory assays for lupus anticoagulant are detailed, as well as modifications of the anticardiolipin antibody assay to improve sensitivity and specificity.
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PMID:Diagnosis of antiphospholipid antibodies. 801 20

The sera patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) were tested, by ELISA, for antibodies to phosphatidylethanolamine (aPE), as well as to cardiolipin (aCL) and compared to healthy blood donors (HBD). Both, SLE and APS patients presented a higher titre of IgM-aPE antibodies than normals, while the IgG and IgA aPE reactivity did not differ. APS patients were characterized by higher IgM-aPE antibody titres than SLE patients. In contrast, the predominant isotype of aCL antibodies in APS patients was IgG. The IgM aPE reactivity was correlated with IgM aCL reactivity, while no correlation was observed between the total IgM values and IgM-aPE binding units of sera tested. Since it was shown that beta 2-glycoprotein-I (beta 2-GPI) contributes to a complex antigen by binding to phospholipids and that this antigen is recognized by antiphospholipid antibodies from autoimmune patients, sera beta 2-GPI levels were measured and correlated to aCL and APE activity. Although APS patients had higher beta 2-GPI levels than SLE patients, no correlation was found between the beta 2-GPI levels and IgG/IgM aCL and IgM-aPE reactivities a finding suggesting that in addition to beta 2-GPI, other cofactors for aPE antibodies may exist. These findings indicate that aPE and aCL antibodies co-exist and that the IgM-isotype is predominant in APS. In addition, the IgA and IgG aPE antibodies appear to occur in low titres in these patients, as well as in normals and may exist as natural autoantibodies. We suggest that the high IgM-aPE antibodies may be viewed as a thymus independent process.
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PMID:Antibodies to phosphatidylethanolamine in antiphospholipid syndrome and systemic lupus erythematosus: their correlation with anticardiolipin antibodies and beta 2 glycoprotein-I plasma levels. 802 4

There is increasing interest in the role of antiphospholipid antibodies in the so-called 'antiphospholipid antibody syndrome' (APS). The two major methods currently employed for detecting the autoantibodies are the solid phase ELISA and the LAI test (inhibition of phospholipid dependent coagulation assay). In our study we have tested the possibility of detecting antiphospholipid antibodies by immunostaining on thin layer chromatography (TLC) plates, since this technique permits the use of pure phospholipid molecules as antigen. Sera were collected from 20 patients with SLE without APS, 20 patients with APS, 20 anti-HIV positive subjects, ten patients with signs of APS but antiphospholipid negative (ELISA), 20 patients with syphilis and 40 matched blood donors. Results showed that only 72.3% of sera containing detectable levels of aCL antibodies in solid phase ELISA were also positive for aCL in TLC immunostaining; these discrepancies may be due to the presence of antibodies reacting with a protein complexed with phospholipid (beta 2-glycoprotein-I) or, alternatively, to the different antigenic presentation of phospholipids on chromatograms compared to the surface of microtitre wells. Furthermore, aCL monoclonal antibody CAL-3, as well as nine sera positive for aCL, also reacted with PS and PE. Previous absorption of these sera with CL micelles completely abolished the reactivity with PS and PE, demonstrating cross-reactivity among these three phospholipids. In conclusion, our findings reveal that TLC immunostaining is more specific, but less sensitive, than ELISA for the detection of antiphospholipid antibodies in human sera.
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PMID:Detection of antiphospholipid antibodies by immunostaining on thin layer chromatography plates. 803 85

We investigated anti-annexin V antibody (aANX) in patients with systemic lupus erythematosus (SLE), and correlated to positivity with lupus anticoagulant (LA)/anticardiolipin antibody (aCL). aANX was positive in 12/47 SLE patients (26%), including 7 with beta 2-glycoprotein 1 (GPI)-dependent aANX. The positivity of aANX was higher in patients with aCL (19%) and LA/aCL (50%) than in those without LA/aCL (10%). From these results, it is concluded that aANX is an autoantibody closely related to LA/aCL, and can be a possible new risk marker for thrombosis.
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PMID:Anti-annexin V antibody in systemic lupus erythematosus patients with lupus anticoagulant and/or anticardiolipin antibody. 766 34

Lupus anticoagulants (LA) have been defined as phospholipid-interfering antibodies. Testing for them has become a frequently requested procedure in coagulation laboratories and new methods have recently become available. Activated partial thromboplastin time (aPTT) reagents with reduced levels or different types of phospholipid provide high sensitivity. Correction procedures resistant to heparin and based on aPTT and dilute Russell's viper venom time (DRVVT) tests with added hexagonal phase phospholipids have improved the specificity of testing. Simplified tests based on venom activators of factor X and prothrombin improve the reliability of LA testing and may facilitate the further categorization of circulating anticoagulants. Recent studies on the mechanism of LA derived from various patients have confirmed their heterogeneity, principally in the protein cofactors involved in their interactions with phospholipids. Perhaps one-third of LA require beta 2-glycoprotein 1 to exert an anticoagulant effect. The remainder may require human prothrombin as suggested from studies with reconstituted clotting factor systems.
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PMID:Some recent developments with lupus anticoagulants. 805 62

We investigated whether or not antiphospholipid antibodies (aPLs; antiphosphadidylserine antibody, aPS; antiphosphatididylinositol antibody, aPI; antiphosphatidic acid antibody, aPA, and antiphosphadidylethanolamine antibody, aPE) were beta 2-glycoprotein-I (GPI)-dependent antibodies like anticardiolipin antibody (aCL) in patients with systemic lupus erythematosus (SLE). None of the patients with syphilis or healthy controls was positive for any GPI-dependent aPL. By contrast, GPI-dependent aCL (40%), aPS (20%), aPI (18%), aPA (12%) and aPE (8%) were detected in patients with SLE. Among these, 4 patients were negative for aCL, but positive for aPS. Those who were positive for more than 2 types of aPL, along with lupus anticoagulant, had a high incidence of arteriovenous thrombosis, fetal loss, thrombocytopenia and biological false-positive reaction to syphilis. From these findings we conclude that GPI-dependent aPLs, other than aCL, are present in patients with SLE, and we should examine more than 2 types of aPL, such as a combination of aCL and aPS, to avoid overlooking aPL. Furthermore, we confirmed that GPI-independent aPL was not rare in SLE patients, but the clinical significance of this type of aPL in this clinical setting is unclear.
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PMID:Detection of beta-2-glycoprotein-I-dependent antiphospholipid antibodies and anti-beta-2-glycoprotein-I antibody in patients with systemic lupus erythematosus and in patients with syphilis. 811 Dec 42

The antiphospholipid syndrome is now well recognized and is separable from SLE, but better quantitation of both the clinical elements and the serologic definitions is still needed. It is likely for autoimmune but not for infection-induced aPL that the antigen is not phospholipid itself but a complex formed by phospholipid and beta 2 glycoprotein I. There are few treatment trials yet published. Those that are available suggest that antiplatelet therapy or anticoagulant therapy are more valuable than is immunosuppression.
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PMID:Antiphospholipid antibody syndrome. 815 4

Nucleotide sequences of variable regions of autoantibodies may help to understand the origin of B cells secreting autoantibodies, both in the context of monoclonal lymphoid proliferations and polyclonal autoimmune diseases. We established the nucleotide sequence of variable genes of four monoclonal IgM secreted by lymphoplasmacytic proliferations and directed to myelin-associated glycoprotein, of five anti-lamin B autoantibodies in patients with a lupus like vasculitis, and of one monoclonal IgM secreted in a chronic lymphocytic leukemia patient and directed to the cardiolipin/beta 2 glycoprotein I complex. A selection process (antigen-driven?) was probably implicated in the origin of autoantibodies in the first two situations although a random process occurred in the last one.
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PMID:Autoantibodies sequencing may help to understand the physiopathology of some monoclonal lymphoid proliferations and autoimmune diseases. 817 28

Anticardiolipin antibodies (ACA) in sera from patients with autoimmune and infectious diseases were tested for binding to beta 2-glycoprotein 1 (gp1) in order to determine whether human gp1 acts as a cofactor for the binding of ACA to cardiolipin (CL) or as an antigen recognized by ACA. While none of the ACA-positive sera tested recognized gp1 by itself, gp1 was necessary for the binding of ACA to CL in sera from four patients with autoimmune diseases. In three of the four sera the presence of lupus anticoagulant (LA) was detected by prolonged partial thromboplastin time (PTT). Examinations using the bovine equivalent of human gp1 contained in fetal calf serum (FCS) and adult bovine serum (ABS) showed that the human protein can be replaced by the bovine equivalent in the enzyme-linked immunosorbent assay (ELISA). Using affinity-purified antibodies directed against the CL-gp1 complex it was shown that the binding of these antibodies is dependent on the concentration of the bovine gp1 equivalent contained in the formed complex. Similar results found with the human gp1 confirmed this assertion. In order to find out which region of gp1 might mediate the binding between ACA and cardiolipin, we examined to what extent selected oligopeptide sequences of gp1 can substitute for the protein. Peptide P2 (representing the amino acids at positions 268-278 of the gp1 molecule) and gp1 showed about the same binding capacity. Histidine in this peptide seems to be essential for the binding to CL as we found decreased binding with peptides modified in this position. Conclusions from this work show that gp1 does not act as a relevant antigen for ACA, but occupies an essential function in the complex formed with cardiolipin for a certain group of ACA.
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PMID:Amino acid sequence of the region of beta 2-glycoprotein 1 (gp1) which mediates binding of autoantibodies to the cardiolipin-gp1 complex in humans. 824 59


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