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)

Three commercial dilute Russell's viper venom time (DRVVT) kits were evaluated at four UK centres experienced at performing lupus anticoagulant (LA) tests. Each centre established a normal reference range for the DRVVT ratio calculated against local pooled normal plasma from 20 healthy normal subjects. Plasma from LA-positive patients and LA-negative thrombophilia patients was also tested. DRVVT ratios and the degree of correction were assessed in a variety of ways to reflect not only the UK national Guidelines, but also the manufacturers' recommendations. The reference range data showed a normal distribution in each case, but considerable variation in the mean and SD between the centres and reagents, with the mean +2SD value ranging from 1.06 to 1.19. The use of an arbitrary DRVVT ratio of < 1.1 as the cut-off value for normality, which is applied in many laboratories, is therefore inappropriate. Although no single kit had a clear overall advantage in terms of sensitivity and specificity, the way in which the screen and confirmation data were analysed had a major impact on the interpretation of the results. A data analysis method employing a mean plus two standard deviations (SDs) cut-off for normality, and judgement regarding confirmation of LA based on a percentage correction of DRVVT ratio, was the simplest and most consistent, with overall sensitivity and specificity values of 81% and 94%, respectively, for uncomplicated LA-positive and LA-negative thrombophilia samples. We conclude that the 1991 BSCH Guidelines are in need of revision, each laboratory should establish its own normal reference range for the DRVVT ratio and a common method should be used for calculating the degree of correction with confirmation reagents, so that LA results can be correctly interpreted between laboratories. Standardizing DRVVT interpretation in this way should improve the consistency of LA detection.
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PMID:The importance of locally derived reference ranges and standardized calculation of dilute Russell's viper venom time results in screening for lupus anticoagulant. 1116 66

The aim of this study was to examine whether the clinical features of antiphospholipid antibody syndrome are associated with anti-cardiolipin and anti-beta2 glycoprotein I antibodies in Indian patients with SLE. Seventy-six patients (71 females), who fulfilled 1982 ACR criteria for SLE, were prospectively studied for the clinical features of antiphospholipid antibody syndrome (APS), and their sera were analysed for the presence of IgG/IgM/IgA anti-cardiolipin antibodies (aCL) by an in-house ELISA and, in 65 of them, for the presence of IgG anti-beta2 glycoprotein I antibodies (anti-beta2 GPI) by a commercial kit. Thirty-nine (51%) patients were positive for aCL, all of which were positive for IgG aCL, either alone (79.6%) or along with IgM and/or IgA. Twenty-seven (69.3%) out of 39 aCL-positive and seven (26.9%) out of 26 aCL-negative sera were positive for IgG antibodies to beta2 GPI. There was a significant correlation (r = 0.66, P < 0.05) between the levels of aCL and anti-beta2 GPI antibodies. Forty-one patients had features of definite or suggestive APS. Thrombocytopenia, recurrent pregnancy loss and CNS manifestations (seizures eight, infarct one) were seen in 20, 13 and nine patients, respectively. Thrombosis of the peripheral vessels was seen in only one patient. Only the presence of seizures was significantly associated with the presence of aCL and anti-beta2 GPI antibodies (P < 0.05). The characteristic association of definite APS (recurrent pregnancy loss and arterial/venous thrombosis) was lacking.
Lupus 2001
PMID:Anti-cardiolipin and anti-beta2 glycoprotein I antibodies in Indian patients with systemic lupus erythematosus: association with the presence of seizures. 1124 9

Several methods are now available for the laboratory assessment of activated protein C resistance (APCR). In this study, we evaluated two activated partial thromboplastin time-based assays [Coatest activated protein C (APC) and Diagen protein C activator (PCA)], with and without predilution of test plasma in factor V-deficient plasma (FVdp) and an amidolytic assay (Immuno Ltd, Vienna, Austria). Testing plasmas from normal volunteers who had received 1-deamino-8-D-arginine vasopressin (DDAVP) also assessed the effect of elevated factor VIII on APCR. In the unmodified clotting tests, the Coatest kit gave overlapping results for normal and heterozygous FV:Q506 samples; some FV:Q506 samples on oral anticoagulant therapy (OAT) were misclassified as normal, and some normal samples with high factor VIII levels would be classified as APC resistant. The unmodified Diagen kit correctly classified these three types of sample, but had the disadvantage that prolonged PCA clotting times gave serious problems with instrument end-point detection. Both kits modified by diluting the samples in FVdp correctly classified all the samples, as well as samples from patients with lupus anticoagulant (LA) and patients receiving heparin. The Immunochrom kit correctly classified the normal and FV:Q506 samples, but would have misclassified most normal persons on OAT as well as some patients with LA or receiving heparin therapy as APC resistant.
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PMID:The impact of oral anticoagulant therapy, factor VIII level and quality of factor V-deficient plasma on three commercial methods for activated protein C resistance. 1141 31

Antiphospholipid antibodies (aPL) have been associated with different diseases. They are defined as a large family of immunoglobulins (Ig) of either alloantibodies or autoantibodies. The autoimmune antibodies are associated with venous and/or arterial thrombosis, thrombocytopenia and recurrent fetal loss in the so-called antiphospholipid syndrome or in systemic lupus erythematosus. These antibodies are directed against proteins or phospholipid-protein complexes. On the contrary, antiphospholipid antibodies (alloantibodies) which are found in infectious diseases sera (syphilis, HIV, and other viral diseases), disappear with illness remission and are directed to phospholipids alone (particularly cardiolipin) and are not associated with thrombosis or recurrent fetal loss. However, the role and type of aPL found during hepatic diseases is still unclear. To investigate the prevalence of autoimmune aPL (IgG and IgM) during different hepatic diseases, we have studied 128 patients with hepatitis C virus, hepatitis B virus and hepatic autoimmune diseases without treatment as well as 40 healthy control subjects. We have used a specific ELISA kit, that uses a mixture of phospholipid instead of cardiolipin alone, and allows a better detection of aPL of the autoimmune type. Our results show that autoimmune aPL are not significantly increased in viral hepatic diseases (2%) or autoimmune diseases of the liver (3%) when compared to the control group (0%).
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PMID:[Low prevalence of autoimmune antiphospholipid antibodies in hepatic diseases]. 1143 2

Although the importance of the anticardiolipin test in diagnosis of antiphospholipid syndrome (APS) is widely accepted, there remains much misunderstanding about the strengths and weaknesses of this assay. Several disorders result in formation of low levels of the antibody, hence the anticardiolipin test is not specific when results are low positive. In general, the higher the anticardiolipin level the greater the likelihood of a diagnosis of APS. Hence there have been numerous efforts to enable reproducible measurement of anticardiolipin levels. Standard calibrators were introduced to construct calibration curves from which levels of unknown samples can be derived. Those standard calibrators were made by mixing varying quantities of high positive with normal sera. More recently, calibrators derived from monoclonal anticardiolipin antibodies have been introduced. There are advantages and disadvantages with both types of calibrators. Determination of a precise and reproducible anticardiolipin level is difficult, whatever the calibrators used, because the assay is dependent on several variable components, any of which may fail on any given day. Utilization of a semi-quantitative measure (low, medium, high) may suffice in most clinical settings and would be less subject to error. Validated ELISA kits may offer greater reproducibility, since there is less variability than bench assays set up in very different laboratories. Whether using a kit or a bench assay, meticulous attention to detail offers the best opportunity for precision and reproducibility.
Lupus 2002
PMID:Revisiting the anticardiolipin test and its standardization. 1209 May 60

Presence in serum of anti-double-stranded deoxyribonucleic acid antibodies (anti-dsDNA) is one of the diagnostic criteria for systemic lupus erythematosus. Anti-single stranded DNA antibodies (anti-ssDNA) also occur, but their clinical significance is unclear. Use of enzyme immunoassay (EIA) kits that are specific for anti-dsDNA is desirable but problematic, since preparation of dsDNA of high integrity is difficult (ie, regions of ssDNA may persist). This study evaluated an EIA kit that uses low Mw plasmid/bacteriophage DNA as a nucleic acid source. Anti-dsDNA results were compared to results obtained by an anti-ssDNA EIA and an immunofluorescent assay (IFA) that uses Crithidia luciliae (specific for anti-dsDNA). Consecutive serum samples (n=139, 88% female) submitted to the clinical laboratory for anti-dsDNA analysis were evaluated. EIA precision was determined at three levels. Intra-assay precision [mean +/- SD (CV)] for anti-dsDNA: 36 +/- 3.5 IU/ml (9.8%); 98 +/- 4.4 (4.5%); and 245 +/- 5.8 (2.4%); and anti-ssDNA. 40 +/- 1.4 U/ml (3.5%); 190 +/- 4.8 (2.5%); and 283 +/- 10.3 (3.7%) (n=8). Inter-assay precision for anti-dsDNA: 36 +/- 6.3 IU/ml (17.5%); 90 +/- 5.9 (6.6%); and 207 +/- 20.9 (10.1%); and anti-ssDNA: 48 +/- 8.2 U/ml (17.0%); 193 +/- 12.7 (6.6%); and 263 +/- 21.5 (8.2%) (n=8). Linearity was assessed with (a) high dsDNA/high ssDNA and (b) low dsDNA/high ssDNA samples (no high dsDNA/low ssDNA samples were identified). Linearity (>200 IU/ml) was found for both sample types with a correlation coefficient (r) of 0.995-0.999. Anti-dsDNA immunoreactivity was not apparent with the low dsDNA/high ssDNA sample. More patients were positive for anti-ssDNA (54%), compared to anti-dsDNA (17%). IFA confirmation (Crithidia) indicated a relative sensitivity and specificity of 94.1% and 93.4% for the anti-dsDNA EIA. IFA positivity correlated with increased anti-dsDNA level: 20% (30-60 IU/ml); 70% (61-200 IU/ml); and 89% (>200 IU/ml). Of specimens that were anti-ssDNA positive and anti-dsDNA negative (n=51), only one was IFA positive. When IFA was compared to an anti-dsDNA EIA kit that used high Mw calf thymus DNA, lower relative specificity (88.2%) and sensitivity (72.6%) was obtained. Anti-ssDNA was found in many false positive specimens (87%).
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PMID:Selective detection of autoimmune antibodies to single- and double-stranded DNA by enzyme immunoassay. 1281 17

Quantitative autoantibody determination has recently can be widely used to confirm the diagnosis of autoimmune diseases, however, there are several problems with the assay methods. As pitfalls in terms of measurement methods, in this report we describe actual examples of a problem related to the analysis and of a large discrepancy between the data obtained by different methods of measurement. In the first example, the reaction solution in the microplate evaporated during the reaction process in automated analysis using an Eitest CA-RF ELISA kit, causing the values in the outermost wells to be significantly higher than in the inner wells. In the second example, there was a large discrepancy between the values obtained when the anti-dsDNA antibody of a systemic lupus erythematosus(SLE) patient was measured by radioimmunoassay(RIA) and by enzyme-linked immunosorbent assay(ELISA). The reason for the discrepancy in the second example may have been related to the method of the RIA, which used 50% ammonium sulfate in the B/F separation, and the possibility that certain patients have autoantibody that recognizes the ELISA solid-phase antigen more strongly. Accordingly, quantitative assay data for anti-dsDNA antibody, which possesses such diversity, should be evaluated with due consideration of the characteristics of the assay method and by checking them against the clinical data.
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PMID:[Pitfalls in laboratory testing for autoantibodies]. 1292 50

A 58-year-old man was admitted with generalized lymphadenopathy. On admission, the patient showed polyclonal hyper-gammopathy in a blood examination, positive results in the direct/indirect Coombs test, and an elevated cold agglutinin titer. Autoimmune thrombocytopenia with a high level of platelet-associated immunoglobulin G complicated the patient's condition. An enzyme immunoassay kit for human immunodeficiency virus (HIV) recombinant proteins p24, gp41, and gp36 showed positive results. Western blot analysis showed the presence of antibodies cross-reacting with HIV p24 gag protein. HIV RNA was not detected by means of a reverse transcriptase-polymerase chain reaction assay, so the patient was not an HIV carrier. Angioimmunoblastic T-cell lymphoma (AILT) was diagnosed on the basis of lymph node biopsy specimens. We speculated that in this case some of the numerous subtypes of polyclonal gamma globulin had coincidentally cross-reacted with HIV p24. Cross-reactive phenomena with HIV in patients with systemic lupus erythematosus have been well investigated, but to our knowledge our patient is the first case of such cross-reactivity involving AILT. Physicians should pay close attention to serologic tests to determine whether the patient truly is a viral carrier.
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PMID:Angioimmunoblastic T-cell lymphoma associated with an antibody to human immunodeficiency virus protein. 1295 12

To discuss the false-positive of serological diagnostic testing for coronavirus antibody in patients with systemic lupus erythematosus(SLE), 66 normal individual and 31 SLE with non-SARS patients were detected for SARS-associated coronavirus (SARS-CoV) antibody and RNA by enzymelinked immunosorbent assays(ELISA) and reverse transcriptase-polymerase chain reaction(RT-PCR). The result showed 2/66 cases(3.0%) were positive of SARS-CoV-IgG antibody and 66 cases were negative of SARS-CoV-IgM antibody in the 66 cases healthy controls; in 31 cases with SLE, positive rates of SARS-CoV-IgG and IgM antibody were 58.1% (18/31) and 29% (9/31), respectively, in which 7 cases(22.6%) were positive of both SARS-CoV-IgG and IgM antibody. All samples of positive SARS-CoV-IgG and IgM antibody were negative by RT-PCR. The ELISA kit coated by non-purification antigen may induce the false-positive of SARS-CoV antibody in patients with SLE. This result suggested that the specificity of ELISA tests for SARS was excellent and has low false-positive rates when using SARS-CoV-IgG and IgM antibody tests. A possible cause of false-positive of SARS-CoV-IgG and IgM antibody in SLE patients is coated antigens with SARS-CoV and Vero-E6 cells in ELISA methods.
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PMID:[Analysis of false-positive associated with antibody tests for SARS-CoV in SLE patients]. 1457 97

Anti-nucleosome (anti-chromatin) antibodies play a key role in the pathogenesis of systemic lupus erythematosus (SLE). The objective of the present study was to determine the clinical significance of anti-nucleosome (anti-chromatin) antibodies, anti-dsDNA antibodies and anti-histone antibodies in patients with SLE in relation to patients with positive nuclear antibodies and healthy controls. We measured anti-nucleosome (anti-chromatin) antibodies, anti-dsDNA antibodies and anti-histone antibodies in 70 patients with SLE, 35 antinuclear antibody (ANA)-positive subjects without autoimmune disease and 35 blood donors. All antibodies were determined by enzyme-linked immunosorbent assay (ELISA). We obtained the receiver operating characteristic (ROC) curve and the area under the curve (AUC) for each autoantibody. Likewise, we obtained the sensitivity, specificity and positive and negative likelihood ratios for each autoantibody. The highest AUC was obtained for anti-nucleosome (0.898) and the lowest AUC for a kit for anti-dsDNA (0.725). Stratification of the control group (ANA-positive subjects without autoimmune disease and blood donors) produced significant changes in the AUCs; all AUCs decreased when ANA-positive patients without autoimmune disease were considered as controls and all AUCs increased when blood donors were considered as controls. These effects were less marked in anti-dsDNA antibodies. We observed discrepancies between kits (anti-nucleosome and anti-chromatin and two for anti-dsDNA). The highest sensitivity for SLE was obtained for anti-nucleosome antibodies (86%) and the highest specificity was obtained for anti-dsDNA antibodies (90%). In conclusion, anti-nucleosome and anti-chromatin kits show different degrees of clinical accuracy due to the cut-off selected by the manufacturer. Once the kits with the best performance and the optimal cut-offs have been selected, anti-nucleosome antibodies and anti-dsDNA antibodies provide similar information in established SLE.
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PMID:Anti-nucleosome, anti-chromatin, anti-dsDNA and anti-histone antibody reactivity in systemic lupus erythematosus. 1508 May 58


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