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 (APA), including lupus anticoagulants (LAC; as detected by in vitro blood clotting tests) and anti-cardiolipin antibodies (ACA; as assayed by solid-phase immunoassay), are strongly associated with recurrent thrombosis, thrombocytopenia, and recurrent fetal loss in some patients with systemic lupus erythematosus (SLE). The combined presence of APA and these clinical manifestations is termed antiphospholipid syndrome (APS). LAC and ACA comprise heterogeneous and somewhat overlapping autoantibody subsets. To date, it is unclear what degree of heterogeneity is present in an individual patient and between patients. To begin to address these issues, we generated three monoclonal LAC antibodies from a patient with SLE and APS. These antibodies were studied for their binding specificities and variable (V) region nucleotide sequences. All three LAC were unreactive with DNA, cardiolipin or other phospholipids. Sequence analysis of these antibodies revealed extensive overlap in their Ig V genes with anti-DNA antibodies and other autoantibodies characteristic of lupus. These data provide the first V gene sequence information on a group of SLE-derived LAC without ACA activity, representative of a similar subset of LAC found in patients with APS.
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PMID:Immunological and molecular analysis of three monoclonal lupus anticoagulant antibodies from a patient with systemic lupus erythematosus. 948 Jul 22

Antiphospholipid antibodies are a heterogeneous group of antibodies, comprising antibodies with different antigen specificity. Prothrombin is one of the antigens which can be detected by antiphospholipid antibodies and therefore anti-prothrombin antibodies belong to the antiphospholipid antibody family. The presence of antiphospholipid antibodies correlates strongly with thromboembolic complications; however a mechanism by which these autoantibodies induce a thrombotic complication in vivo is not understood. The classic assays for the detection of antiphospholipid antibodies (LAC and anticardiolipin ELISAs) aim to measure all the antiphospholipid antibodies present in the samples without making a distinction between the different subspecificities of the antibodies present in one single sample. Moreover, most of the in-vitro studies performed were carried out with total IgGs, which contain a mixture of antibodies. The absence of an accurate characterization of the plasma samples and the lack of specificity of the IgGs used in in-vitro tests makes it difficult to determine the contribution of antiprothrombin antibodies to the thrombotic complications. Here we review and critically analyse the literature regarding the clinical relevance of the presence of antiprothrombin antibodies and the possible participation of these antibodies in the pathogenesis of the thrombotic complications.
Lupus 1998
PMID:Anti-prothrombin antibodies and their relation with thrombosis and lupus anticoagulant. 981 69

We describe two patients whose initial presentation of systemic lupus erythematosus (SLE) was accompanied by haemorrhagic episodes and significant coagulopathy. Further investigation demonstrated positive lupus anticoagulant and decreased Factor II (prothrombin) activity. Both patients were diagnosed with lupus anticoagulant-hypoprothrombinemia syndrome (LAC-HPS) as a result of non-neutralizing antibodies directed against Factor II. LAC-HPS is a rare clinical entity that can occur in association with SLE, transient viral infections, drug reactions or even in healthy individuals. Mixing studies, which can be affected by other coagulation factor inhibitors, play an important role in the diagnosis of LAC-HPS. Factor VII level was decreased in the second patient, a finding that has not previously been reported in association with SLE. In both patients, bleeding stopped promptly and coagulation studies improved significantly with high dose corticosteroids. We discuss the pathogenesis, diagnosis and management of LAC-HPS in patients with SLE.
Lupus 1999
PMID:Lupus anticoagulant-hypoprothrombinemia syndrome associated with systemic lupus erythematosus: report of 2 cases and review of literature. 1048 36

Patients with systemic lupus erythematosus with established disease have poorer pregnancy outcomes than do women with later onset disease. Active renal disease and maternal hypertension are important predictors of fetal loss and premature birth, respectively. Placental pathology in SLE patients is characterized by decidual vasculopathy and infarction, and in APLS patients, infarction can be extensive. Maternal anti-52 kD SSA/Ro by immunoblot continues to be an important risk factor for having a child with heart block. The risk of having a subsequent child with congenital heart block ranges between 12-16%. Childhood morbidity with heart block is high, with 63% eventually requiring pacemakers. In APLS, antiB2GP-I antibodies can have a significant role in the diagnosis, especially when the traditional assays for aCL antibodies and LAC are negative. Some obstetricians have found that IVIG improves the birthrate in aPL positive women who have recurrent spontaneous abortions after IVF.
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PMID:Pregnancy in lupus. 1050 53

A 57-year-old woman was under treatment for epilepsy with lamotrigine 2 mg/kg/d since 1996. In April 1998 she was admitted to the Rheumatology Unit for arthralgias affecting the small joints of the hands, wrists and knees, erythematosus skin rash and myalgias. She referred a vascular abnormality at the hands exposed to cold, compatible with Raynaud's phenomenon. Serum antinuclear antibodies (ANA) were positive (1:320, speckled pattern); moreover, a positivity for anti-Ro/SSA was observed. Rheumatoid factor was negative, serum complement was normal. LAC and anticardiolipin antibodies were negative. Drug-related lupus diagnosis was made with resolution of symptoms and gradual normalisation of positivity of ANA and anti-Ro/SSA upon lamotrigine withdrawal. To our knowledge, this is the first case report of an association between lamotrigine and the onset of SLE (systemic lupus erythematosus).
Lupus 2000
PMID:Lamotrigine-induced lupus. 1103 25

Three mosquito-borne human encephalitis viruses (eastern equine encephalitis virus [EEE], St. Louis encephalitis virus [SLE], and La Crosse encephalitis virus [LAC]) are sympatric in the southeastern United States. However, little is known concerning the temporal and spatial pattern of the distribution of these viruses in this area. As part of surveillance activities to detect the transmission of these 3 viruses in the Tennessee Valley area, we developed a single-tube multiplex reverse transcriptase polymerase chain reaction (RT-PCR) assay capable of detecting these 3 mosquito-borne viruses in a single reaction. Three viruses were differentiated by size of amplified products. Sensitivities of the multiplex RT-PCR assay for SLE, EEE, and LAC were 1-3 log median tissue culture infective doses per pool, roughly comparable to the reported sensitivity of PCR detection assays for the individual viruses, and 1 log more sensitive than antigen-capture assays for SLE and EEE. The sensitivity of the multiplex PCR was not changed significantly when carried out in the presence of extracts prepared from 50 uninfected mosquitoes. The cost of the assay is estimated at $2.98 per test, similar to the cost of other RT-PCR-based assays for viruses. However, adaptation of the RT-PCR to a multiplex format adds less than $0.01 to the per-unit cost of an RT-PCR assay targeting a single virus species. Analysis of these data suggests that the single-tube multiplex RT-PCR assay represents a sensitive, specific, cost-effective, and rapid method for monitoring activities of the 3 endemic mosquito-borne human encephalitis viruses in mosquito populations in the southeastern United States.
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PMID:Simultaneous detection of three mosquito-borne encephalitis viruses (eastern equine, La Crosse, and St. Louis) with a single-tube multiplex reverse transcriptase polymerase chain reaction assay. 1199 26

Not only antiphospholipid antibodies (aPLs) but also other factors should be considered in assessing the risk of thrombosis development in patients with systemic lupus erythematosus (SLE) and antiphospholipid antibodies (aPLs). The kinds of risk factors, including past history of thrombotic event (PHTE), hypertension, hypercholesterolemia, diabetes mellitus (DM), obesity, and smoking, in conjunction with aPLs, that contribute to the development of new thrombotic events in patients with SLE and aPLs were studied prospectively over a 5-year observation period. One-hundred and sixty-six Japanese patients with SLE (55 patients with aPLs and 111 patients without aPLs) were examined and followed up for 5 years. Five major risk factors for ischemic coronary disease and stroke according to the Framingham heart cohort study were evaluated objectively in these patients. A significant difference was seen for 4 factors: past history of thrombotic event (PHTE; odds ratio: 101.93; 95% confidence interval: 12.29-845.22; p < 0.0001), hypertension (odds ratio: 8.87; 95% CI: 2.58-30.53; p < 0.001), DM (odds ratio: 5.42; 95% CI: 1.44-20.46; p < 0.05), and lupus anticoagulant (LAC; odds ratio: 47.41; 95% CI: 5.88-382.03, p < 0.0001) as aPLs, when the incidence of these risk factors was compared between patients with and without new thrombotic events. Furthermore, PHTE (odds ratio: 30.19, 95% CI: 1.33-683.13), hypertension (odds ratio: 15.44; 95% CI: 1.77-134.80), and LAC (odds ratio: 14.11; 95% CI: 0.48-412.42) showed higher odds ratios than DM (odds ratio: 11.53; 95% CI: 0.83-159.94) on multivariate logistic analysis as well as analysis of the combination of risk factors, suggesting that these are important risk factors for the development of new thrombotic events in patients with SLE and aPLs.
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PMID:Risk factors for recurrent thrombosis: prospective study of a cohort of Japanese systemic lupus erythematosus. 1619

The concurrence of antiphospholipid (aPL) antibodies and thrombosis or pregnancy loss defines the 'antiphospholipid syndrome' (APS). The Sydney update of the classification criteria for definite APS diagnosis introduced numerous ameliorations to the previous preliminary consensus statement. Clinical criteria are now better defined as vascular thrombosis must be diagnosed on the basis of objective criteria. Moreover,additional risk factors for thrombosis or pregnancy loss must be taken into account before the diagnosis is made and should be described in detail in scientific reports. As far as laboratory criteria are concerned,the lack of standardization and the misinterpretation of results remain major problems often leading to overdiagnosis. A single positive test result out of the possible assays determining aPL antibodies (Lupus Anticoagulant, LAC, anticardiolipin, aCL and anti. beta2-Glycoprotein I, beta2-GPI, antibodies) is still sufficient,according to the Sydney criteria, to justify a diagnosis of APS. Nevertheless single test positivity may result in overdiagnosis or identification of low risk patients and use of all three tests seems more reasonable. Multiple positivity or (better) triple positivity in our experience allows for the identification of high risk patients for possible recurrence. In the near future, coagulation tests discriminating between a beta2-GPI and anti-prothrombin LAC may be useful in identifying high risk patients.
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PMID:The diagnosis of the antiphospholipid syndrome. 1685 67

Brain magnetic resonance imaging (MRI) studies in migraine patients have demonstrated lesions consisting of focal regions of increased signal intensity within the white matter. Antiphospholipid antibodies are known to have a role in many diseases including migraine. The aim of the present study was to ascertain the relationship between MRI-visualized cerebral focal hyperintense lesions and serum antiphospholipid antibody levels, as well as blood coagulation parameters in migraine patients. One hundred and two (77 females, 25 males, mean age 33.8 +/- 11.1) consecutive migraine patients and a control group of 94 (70 females, 24 males, mean age 33.2 +/- 10.8) healthy subjects were enrolled. All individuals underwent brain MRI. Complete blood examinations, autoantibodies, antiphospholipids antibodies including anticardiolipin and lupus anticoagulant (aCL, LAC), antithrombin III, Protein C and S serum levels were ascertained in the subjects who presented white matter lesions on MRI. Twenty-seven (26.4%) migraine patients and six (6.3%) healthy subjects in the control group showed focal regions of increased intensity signal within cerebral white matter (odds ratio 5.3, 95% CI: 1.98-16.36). In migraine patients with white matter lesions, antiphospholipid antibodies were not detected and serum levels of antithrombin III, and proteins C and S were normal. White matter lesions in migraine patients are fairly common. This finding is not associated with antiphospholipid antibodies or abnormal coagulation parameters. The significance of such lesions at present remains unclear.
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PMID:Brain MRI white matter lesions in migraine patients: is there a relationship with antiphospholipid antibodies and coagulation parameters? 1711 21

The combined presence of anti-phospholipid Ab (aPL), thrombosis, and/or fetal loss is recognized as the antiphospholipid syndrome (APS). aPL include anti-cardiolipin Ab (aCL) and/or lupus anticoagulants (LAC, detected as Ig that prolong certain in vitro phospholipid (PL)-restricted blood clotting tests); both aCL and LAC are the diagnostic Ab for APS. Studies show that aPL represent a heterogeneous group of Ab, which recognize various PL, PL-binding plasma proteins, and/or PL-protein complexes. Recently, we found that five of seven patient-derived IgG monoclonal aCL react with thrombin, activated protein C, and plasmin. All three proteins are trypsin-like serine proteases (SP), and are highly homologous in their catalytic domains. Importantly, among these SP autoantigens, the reactive aCL bind to plasmin with the highest affinity, suggesting that plasmin may serve as a major driving autoantigen for some aCL in approximately 30% of APS patients who are positive for IgG anti-plasmin Ab. To test this hypothesis, we immunized BALB/c mice with human plasmin and analyzed immune sera for aCL activity and reactivity with relevant SP. We found that some immune sera displayed aCL activity and/or bound to test SP. Subsequently, eight mAb were obtained and studied. The results revealed that one mAb displayed the aCL and the LAC activities and induced fetal loss when injected into pregnant mice. Immunohistological analyses of placentas revealed extensive deposits of activated C3 components. Combined, these data demonstrate that plasmin may serve as a driving Ag for some pathogenic aPL.
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PMID:Some plasmin-induced antibodies bind to cardiolipin, display lupus anticoagulant activity and induce fetal loss in mice. 1740 20


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