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)

"Antiphospholipid" antibodies (aPL) are a heterogenous group of autoantibodies with clinical importance because of their association with thrombotic events, both venous and arterial. Traditionally, aPL have been assayed using phospholipid-dependent tests and are classified as lupus anticoagulants and anticardiolipin antibodies (ACA), based on the method of detection. Most antibodies associated with the aPL syndrome and detected in standard assays are actually directed against two phospholipid-binding plasma proteins, beta 2 glycoprotein I and prothrombin. These antibodies can also be detected in immunoassays (ELISA) utilizing purified protein antigens, in the absence of phospholipids. The main advantage of beta 2 GPI-ELISA compared with conventional cardiolipin-ELISA appearing from initial clinical studies is greater specificity for the aPL syndrome, due to (i) ignorance of "authentic" ACA that interact directly with cardiolipin; (ii) detection of species specific anti-beta 2 GPI antibodies poorly reactive with bovine beta 2 GPI in the cardiolipin-ELISA. Other proteins proposed as target antigens of aPL are protein C, protein S, annexin V, high- and low-molecular weight kininogens, the latter being involved in the binding of antibodies to phosphatidylethanolamine. The possibility that particular autoantibodies (or combinations of autoantibodies) explain the observed clinical spectrum of the aPL syndrome is attractive, but much remains to be learned about their pathogenicity and origin in order to improve diagnosis and therapy.
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PMID:[New targets of antiphospholipid antibodies]. 916 56

Relapsing polychondritis (RP) is an extremely rare multisystemic disease thought to be of autoimmune origin. In order to assess if RP is associated with anti-phospholipid antibodies (aPL), clinical data and sera of 21 patients with RP were collected in a multicentre study. Concentration of anti-cardiolipin antibodies (aCL) (IgG-, IgM- and IgA-isotypes), anti-phosphatidylserine-antibodies (aPS) (IgG- and IgM-isotypes) and anti-beta-2-glycoprotein I-antibodies (a beta 2 GPI) were measured by ELISA. In eight patients aCL were found to be elevated. One patient had elevated aPS. No patient had elevated a beta 2 GPI. No patient had clinical signs and symptoms of a aPL syndrome. Interestingly, the two RP patients with the highest aPL had concomitant systemic lupus erythematosus (SLE). Therefore the presence of elevated aPL in RP is probably more closely related to an associated SLE than to RP itself. There is no convincing evidence that aPL are associated with RP.
Lupus 1998
PMID:Anti-phospholipid-antibodies in patients with relapsing polychondritis. 949 43

A rare SLE patient with central nervous system involvement (CNS-SLE) who relapsed presenting new symptoms associated with the development of serum anti-Sm antibody and was then successfully treated with cyclophosphamide (CY) pulse therapy is presented here. A 47-years old housewife was admitted to Kushiro City General Hospital because of fever, limb erythema and drowsy consciousness in September 1995. On the basis of convulsion, proteinuria, leukopenia, thrombopenia, serum positive tests for both anti-nuclear antibody and anti-SSA antibody and low complement levels, as well as elevations of IgG index and IL-6 in the cerebrospinal fluid (CSF), she was diagnosed as having CNS-SLE. Serum tests for anti CL-beta 2 GPI antibody and lupus anticoaglant was negative. Serum test for HBs antigen was positive. She was treated successfully with methylprednisolone (mPSL) pulse therapy and plasma exchange (PE). Prednisolone was gradually tapered to the dosage of 17.5 mg per day and she was discharged in April 1996. She was re-admitted because of fever, an exacerbation of skin eruption and arthralgia in October 1996. Serum anti-Sm antibody was found to be positive. mPSL pulse therapy was not effective. On the basis of hallucination and elevations of IgG index and IL-6 in the CSF, a diagnosis of relapsed CNS-SLE was made. However the level of IFN-alpha in the CSF was normal. Although PE was not effective, CY pulse therapy was markedly effective.
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PMID:[A recovered case of SLE with central nervous system involvement who relapsed presenting new symptoms associated with development of serum anti-Sm antibody]. 956 77

Antibodies to beta 2-glycoprotein in the serum of patients with antiphospholipid syndrome (APS) were found by many investigators, but their results appeared contraversional. We studied clinical significance of antibodies to beta 2-glycoprotein I (anti-beta 2-GPI) in patients with SLE. 69 patients with verified SLE were examined for lupus anticoagulant (LA), antibodies to cardiolipin (aCL) and anti-beta 2-GPI. 44(65%), 46(67%), 49(71%), 19(28%), 16(23%) patients were positive for LA, IgG-aCL, IgM-aCL, IgG-anti-beta 2-GPI and IgM-anti-beta 2-GPI, respectively. Hyperproduction of IgG-anti-beta 2-GPI correlated with APS development as a whole, its separate clinical symptoms (venous and arterial thromboembolism, obstetric pathology and thrombocytopenia) and some comcomitant clinical signs (trophic crural ulcer, hemolytic anemia, valvular heart disorders). Moreover, an increase in concentration of IgM-anti-beta 2-GPI was associated with habitual abortion. Both isotypes of anti-beta 2-GPI occurred more frequently in the sera positive by LA and aCL. It is interesting that we discovered IgG-anti-beta 2-GPI more often in early than late postthrombolytic period. Thus, anti-2b2-GPI is a new serological marker of APS. Its detection is clinically important for upgrading diagnosis of APS.
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PMID:[Antibodies to beta2-glycoprotein I in systemic lupus erythematosus: new laboratory marker of antiphospholipid syndrome]. 957 46

Antiphospholipid syndrome (APLS), is defined as the presence of antiphospholipid antibodies (APLA) associated with clinical phenomena of arterial or venous thrombosis, recurrent spontaneous abortions and thrombocytopenia. APLA represent the family of antibodies of different specificity. They are mostly directed to various anionic phospholipids (cardiolipin, phosphatidylcholine, phosphatidylserine, phosphatidyl acid and phosphatidyl ethanolamine). The part of APLA is directed towards epitope at the structurally changed beta-2-GPI, the so-called anti beta-2-GPI antibodies and the hypothesis was established that the subgroup of APLA was directed towards complex of beta-2-GPI with the phospholipids and oxidized lipoproteins of high and very low density. This could explain the clinically observed association of mutual onset of thrombosis and atherosclerosis. The most frequent target tissues for APLA are endothelial cells, thrombocytes, monocytes, natural anticoagulant system and placenta. APLA can be detected in a serum with one of the following assays: testing of lupus anticoagulant presence, determination of anticardiolipin antibodies (ACLA) concentration by ELISA and by testing the false positivity of VDRL test (standard test for syphilis). The pathological base for so-called vasculopathy in APLS are arterial and venous thrombosis. Clinical manifestations of APLS are mainly the result of blood vessels' occlusion but the thrombotic mass deposition on the surface of the heart valves may also occur. Clinically APLS can be divided into primary and secondary one, and manifestations of the secondary APLS are mainly expressed in the patients with SLE. Some clinical and serological variants of primary APLS were also described. The tendency for thrombotic process as a crucial characteristic of the syndrome and the lack of inflammation, imposes the choice of antithrombotic and anticoagulant therapy.
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PMID:[The antiphospholipid syndrome--yesterday, today, tomorrow]. 962 52

Sera from 20 patients with antiphospholipid syndrome (APS), primary or secondary to systemic lupus erythematosus (SLE), or with SLE, were assayed by immunoblot analysis for anti-beta2-glycoprotein I antibodies (abeta2-GPI), and by indirect immunofluorescence (IIF) technique for reactivity with astrocyte and neuron cell lines and with histological sections of human brain biopsies and monkey cerebellum. Six sera from healthy donors were studied as a control. Eleven out of the 20 patient sera contained abeta2-GPI and were immunoreactive with astrocytes and neurons, both in culture and in the histological sections, and with the endotheliocytes of the microvessels present in the histological sections. Cell localization and the pattern of immune reaction were similar to those obtained with a monoclonal antibody abeta2-GPI. Eight of the remaining patient sera, found abeta2-GPI-, did not react with the nervous substrates (and the control sera), while one exhibited immunoreactivity analogous to the abeta2-GPI+ sera. The interference of anticardiolipin antibodies (aCL) in the immunoreactivity with the nervous substrates was excluded since aCL were present in all patient sera and no immune reaction was observed in the histological sections incubated with a monoclonal aCL. Therefore, the binding of abeta2-GPI from patients to cells of the central nervous system (CNS) occurs independently from aCL. This issue may be relevant to further evaluate the potential pathogenetic role of abeta2-GPI in the CNS damage of APS-like conditions.
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PMID:Serum anti-beta2-glycoprotein I antibodies from patients with antiphospholipid antibody syndrome bind central nervous system cells. 980 25

The relationship between presence of anti-beta2-glycoprotein I autoantibodies (abeta2-GPI) and history of thrombosis is now widely known. However, differences in the methodology of abeta2-GPI detection have made the comparison of data from different laboratories extremely difficult. We discuss the significance of abeta2-GPI of the IgG, IgM and IgA isotypes, and our approach to developing an easier and more reproducible method for the detection of this autoantibody. In addition, we present data that shows that commercially available enzyme immunoassay plates differ regarding detectability of abeta2-GPI. Since the clinical significance of this heterogeneity is presently unclear, the set-up of the detection systems and interpretation of data need great care.
Lupus 1998
PMID:Anti-beta2-glycoprotein I antibodies. 981 83

Beta2-Glycoprotein I (beta2-GPI) is a major antigen for anticardiolipin antibodies (aCL) induced in patients with antiphospholipid syndrome and their antigenic epitopes are cryptic. The epitopes appear on the surface of beta2-GPI molecule only when beta2-GPI interacts with lipid membranes containing negatively charged phospholipids or polyoxygenated polystyrene surface. Our data also indicated that CuSO4-oxidized low density lipoproteins (oxLDL) are subsequently targeted by beta2-GPI and aCL; however, malonedialdehyde (MDA)-modified LDL were recognized neither by beta2-GPI nor aCL. Beta2-GPI binding to LDL was rapidly increased by incubation with CuSO4. Oxidation of lipoproteins was accompanied with the increment of thiobarbituric acid-reactive substances (TBARS) and denature of apolipoprotein. Ligands on LDL for beta2-GPI seemed to be intermediate oxidative derivatives which were extractable into the chloroform phase by Bligh and Dyer's extraction, but not MDA. Further, immune responses against beta2-GPI, as an anti-atherogenic protein, were demonstrated to induce atherogenic effect in in vitro oxLDL uptake by macrophages.
Lupus 1998
PMID:Antiphospholipid antibodies and atherosclerosis. 981 91

The aim of this study was to determine if the measurement of anti-beta2-glycoprotein I antibodies (abeta2-GPI) in serum levels contributes to the better characterization of the clinical situation of patients with antiphospholipid syndrome (APS). For this purpose abeta2-GPI of both isotypes was measured in 42 patients with APS and 32 SLE patients without APS. Clinical records of all patients were thoroughly reviewed. The presence of abeta2-GPI was correlated with the clinical manifestations of APS and compared with the presence of anticardiolipin antibodies (aCL) and lupus anticoagulant (LA) activity. There was a positive correlation between levels of aCL and abeta2-GPI for both IgG and IgM isotypes (rho of Spearman=0.82 and 0. 64 respectively, P=0.0001). Both antibodies presented significantly higher titres in LA positive patients (P<0.05). The specificity for APS was 91% for IgG abeta2-GPI vs 75% for IgG aCL and 87% for IgM abeta2-GPI vs 81% for IgM aCL. 68% of patients with thrombosis of 100% of patients with thrombocytopenia showed positive tests for all three markers (aCL, LA, abeta2-GPI). Simultaneous presence of circulating LA and high titres of both aCL and abeta2-GPI identify a subset of patients with primary APS (PAPS) who have a more severe clinical course of the disease. Although the specificity of abeta2-GPI IgG is higher than that of aCL IgG, when all three tests are performed abeta2-GPI testing provides only additional information to that of aCL and LA. Therefore, we concluded that the abeta2-GPI test should not be considered as a substitute for conventional LA or aCL assays. However, performance of abeta2-GPI seems to be important in PAPS with high aCL titres, to alert the physician about the risk for the worst course of the illness.
Lupus 1999
PMID:Do antibodies to beta2-glycoprotein 1 contribute to the better characterization of the antiphospholipid syndrome? 1048 10

Increased prevalence of anti-phospholipid antibodies (aPL) and increased levels of lipid peroxidation have been described in patients with HIV infection. To assess the binding specificity and avidity of aPL antibodies in HIV infection, sera from 44 HIV-1 infected patients were evaluated for antibodies to cardiolipin (aCL), phosphatidyl serine (aPS), phosphatidyl inositol (aPI) and phosphatidyl choline (aPC) using enzyme linked immunosorbent assay (ELISA) methods. Sera from 30 patients with systemic lupus erythematosus (SLE), but without features of anti-phospholipid syndrome (APS) (SLE/non APS), six with SLE and secondary APS, (SLE/APS) and 11 with primary APS (PAPS) were also evaluated as controls. The resistance of the aPL antibody binding to dissociating agents was evaluated by treating the ELISA wells, after serum incubation with 2 M urea or 0.6 M NaCl for 10 min. An anti-beta2-glycoprotein-I (beta2-GPI) ELISA was used to assess serum reactivity against beta2-GPI, a plasma protein considered as the true antigen of aCL antibodies occurring in APS and SLE patients. The prevalence of aCL, aPS, aPI and aPC antibodies in HIV-1 infection was 36%, 56%, 34% and 43% respectively, which was comparable to that found in SLE/APS and PAPS patients and significantly higher than that observed in SLE/non-APS patients. Anti-beta2-GPI antibodies occurred in 5% of HIV-1 infected vs. 17% in SLE/non-APS (P=0.11), 50% in SLE/APS (P=0.009) and 70% in PAPS patients (P=0.0014). A significant decrease of aPL binding after urea and NaCl treatment was observed in the sera of HIV-1-infected, compared to that of APS patients, indicating that aPL antibodies from HIV-1 infected individuals have low resistance to dissociating agents. In conclusion, aPL antibodies (1) occur in HIV-1 infection; (2) tend to recognize various phospholipids but not beta2-GPI; and (3) are of low resistance to dissociating agents-a finding probably reflecting low antibody avidity. Finally, these, like the autoimmune-type aCL antibodies, tend to recognize the oxidized CL-a finding probably indicating autoantibody generation as a result of neoepitope formation by oxidized PLs.
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PMID:Anti-phospholipid antibodies in HIV infection and SLE with or without anti-phospholipid syndrome: comparisons of phospholipid specificity, avidity and reactivity with beta2-GPI. 1055 Feb 22


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