Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus.
TL;DR: In 1992, Piette and colleagues suggested that the ACR revised criteria be reevaluated in light of the above discoveries, and the presence and clinical associations or antiphospholipid antibodies in patients with SLE was suggested.
Abstract: In 1982, the Diagnostic and Therapeutic Criteria Committee of the American College of Rheumatology (ACR)published revised criteria for the classification of systemiclupus erythematosus (SLE) (1). During the ensuing decade several investigators, including Drs. Graham Hughes and Donato Alarcon-Segovia, among others, have described the presence and clinical associations or antiphospholipid antibodies in patients with SLE, as well as the occurrence of theprimary antiphospholipid syndrome (2-5). In 1992, Piette and colleagues suggested that the ACR revised criteria be reevaluated in light of the above discoveries (6).
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TL;DR: The genetic causality of SLE arises from multiple tissues with the top causal tissue being the liver, followed by brain basal ganglia, adrenal gland and whole blood, and this study defines distinct susceptibility and activity/severity signatures in SLE that may facilitate diagnosis, monitoring, and personalized therapy.
Abstract: Recent genetic and genomics approaches have yielded novel insights in the pathogenesis of Systemic Lupus Erythematosus (SLE) but the diagnosis, monitoring and treatment still remain largely empirical. We reasoned that molecular characterization of SLE by whole blood transcriptomics may facilitate early diagnosis and personalized therapy. To this end, we analyzed genotypes and RNA-seq in 142 patients and 58 matched healthy individuals to define the global transcriptional signature of SLE. By controlling for the estimated proportions of circulating immune cell types, we show that the Interferon (IFN) and p53 pathways are robustly expressed. We also report cell-specific, disease-dependent regulation of gene expression and define a core/susceptibility and a flare/activity disease expression signature, with oxidative phosphorylation, ribosome regulation and cell cycle pathways being enriched in lupus flares. Using these data, we define a novel index of disease activity/severity by combining the validated Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) with a new variable derived from principal component analysis (PCA) of RNA-seq data. We also delineate unique signatures across disease endo-phenotypes whereby active nephritis exhibits the most extensive changes in transcriptome, including prominent drugable signatures such as granulocyte and plasmablast/plasma cell activation. The substantial differences in gene expression between SLE and healthy individuals enables the classification of disease versus healthy status with median sensitivity and specificity of 83% and 100%, respectively. We explored the genetic regulation of blood transcriptome in SLE and found 3142 cis-expression quantitative trait loci (eQTLs). By integration of SLE genome-wide association study (GWAS) signals and eQTLs from 44 tissues from the Genotype-Tissue Expression (GTEx) cosortium, we demonstrate that the genetic causality of SLE arises from multiple tissues with the top causal tissue being the liver, followed by brain basal ganglia, adrenal gland and whole blood. Collectively, our study defines distinct susceptibility and activity/severity signatures in SLE that may facilitate diagnosis, monitoring, and personalized therapy.
01 Jan 2011
Peer Review•
TL;DR: In this article , the authors examined the frequency, causes, and predictors of mortality in a cohort of Egyptian systemic lupus erythematosus (SLE) patients and compared mortality causes and the survival rate in our cohort to African, Arabic, and Mediterranean studies.
Abstract: Objectives: The study aimed to examine the frequency, causes, and predictors of mortality in a cohort of Egyptian systemic lupus erythematosus (SLE) patients and compare mortality causes and the survival rate in our cohort to African, Arabic, and Mediterranean studies. Patients and methods: In this retrospective study, a review of medical records of 563 SLE patients (516 females, 47 males; median of age: 32 [IQR: 26-38 years]; range, 14 to 63 years) fulfilling the 1997 American College of Rheumatology (ACR) criteria between January 2015 and December 2019 was done. The data extracted included demographic, clinical, and laboratory features, treatments used, disease activity as measured by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and damage index as measured by Systemic Lupus International Collaborating Clinics (SLICC) damage index. Causes of mortality were also reported. Results: Out of 563 reviewed medical records, 50 (8.9%) patients died. Infection (28%) and organ damage (18%) were the most commonly reported causes of death. Multivariate Cox regression analysis showed that patients with cardiac manifestations, renal failure, those receiving higher doses of either oral (in their last visit) or intravenous (higher cumulative pulse steroids) steroids were at increased risk of mortality (p=0.011, p<0.001, p=0.01, and p<0.001, respectively; 95% confidence intervals 7.2, 63.9, 1.2, and 1.09, respectively). The overall survival at 5, 10, 15, and 20 years was 96.6%, 93.3%, 91.0%, and 83.2%, respectively, and 56.2% at 25 years until the end of the follow-up. Conclusion: Cardiac manifestations, renal failure, and higher steroid doses were independent predictors of mortality in our cohort. As in most African countries, infection was the main cause of death in our study; however, the mortality rate and the five-year survival among our cohort were better than in African (sub-Saharan) countries and similar to Arabic and Mediterranean countries.
TL;DR: MZR may be a valuable option as an immunosuppressive agent for SLE, as well as MMF, and the adverse events of MZR, whose profile differs from MMF are comparable to or less than those of MMF.
Abstract: Background: Mizoribine (MZR) is an immunosuppressive agent that selectively inhibits inosine monophosphate dehydrogenase; its actions are considerably similar to those of mycophenolate mofetil (MMF). This study aimed to clarify whether MZR can be a good treatment option for systemic lupus erythematosus (SLE) and to compare the efficacy and safety of MZR and MMF in patients with active SLE. Methods: We retrospectively compared the efficacy, continuation rate, and safety of MZR (52 patients) and MMF (31 patients) after adjusting for stabilized inverse probability of treatment weighting based on propensity scores. The efficacy endpoints were as follows: cumulative incidence of lupus low disease activity state (LLDAS) or remission attainment and flares and change in prednisolone dose over 2 years. Drug continuation rates were defined as the time from drug initiation to discontinuation for any cause, owing to the lack of efficacy, or owing to adverse events. The safety endpoint was the frequency of adverse events. Results: Overall, 25 (48.1%) and 13 (25.0%) patients in the MZR group and 18 (58.1%) and 15 (48.3%) in the MMF group achieved LLDAS and remission during the follow-up period, respectively; thus, the cumulative incidence of LLDAS and remission attainment of the two groups was similar after adjustment. Prednisolone dose was steadily reduced in both the groups, and the change in prednisolone dose was nearly identical between the two groups. Drug discontinuation rate due to adverse events and the frequency of all adverse events and infections were higher in the MMF group than in the MZR group, albeit without significance after adjustment. Conclusion: MZR is as effective as MMF in controlling SLE activity. The adverse events of MZR, whose profile differs from MMF, are comparable to or less than those of MMF. MZR may be a valuable option as an immunosuppressive agent for SLE, as well as MMF.
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TL;DR: The 1971 preliminary criteria for the classification of systemic lupus erythematosus (SLE) were revised and updated to incorporate new immunologic knowledge and improve disease classification and showed gains in sensitivity and specificity.
Abstract: The 1971 preliminary criteria for the classification of systemic lupus erythematosus (SLE) were revised and updated to incorporate new immunologic knowledge and improve disease classification. The 1982 revised criteria include fluorescence antinuclear antibody and antibody to native DNA and Sm antigen. Some criteria involving the same organ systems were aggregated into single criteria. Raynaud's phenomenon and alopecia were not included in the 1982 revised criteria because of low sensitivity and specificity. The new criteria were 96% sensitive and 96% specific when tested with SLE and control patient data gathered from 18 participating clinics. When compared with the 1971 criteria, the 1982 revised criteria showed gains in sensitivity and specificity.
14,272 citations
TL;DR: A new solid-phase radioimmunoassay for the detection of anticardiolipin antibodies is 200-400 times more sensitive than the precipitation method used in the Venereal Disease Reference Laboratory test and appears to have predictive value for thrombosis in SLE and related disorders.
1,324 citations
1,239 citations
TL;DR: The group of patients presented appears to be closely related, but distinctly separate from SLE, with a history of deep vein thromboses and a family history of SLE or a familial clotting tendency in a minority.
972 citations
Journal Article•
TL;DR: This study shows that properly performed ELISA or SRIA assays can be used to provide an accurate, reproducible, and quantitative measure of IgG and IgM aCL concentration in serum samples.
Abstract: Thirty laboratories from institutions in Britain, France, Italy, The Netherlands, New Zealand, Sweden and the USA participated in a workshop to evaluate the anti-cardiolipin (aCL) test. Participants were asked to measure IgG and IgM aCL in seven samples on each of three separate days. The seven samples were prepared so that IgG and IgM aCL concentrations were known before distribution. Twenty-three of 30 laboratories measuring IgG aCL had significant regression slopes (P less than 0.001) when optical absorbance readings or counts per minute were compared with IgG aCL concentration. Twenty-four of 28 laboratories measuring IgM aCL had significant regression slopes (P less than 0.001). Coefficient of determination (R2) ranged from 81.1% to 98.7% for laboratories with valid IgG aCL assays and from 48.0% to 96.7% for valid IgM aCL assays. Valid assays had in common the use of 10% fetal calf or 10% adult bovine serum in PBS. Assays that were not valid had in common the use of PBS, PBS-Tween, or 0.3% gelatin as diluents. All laboratories with valid assays defined samples with high and moderate aCL levels as positive but there was no consensus about low positive samples. This study shows that properly performed ELISA or SRIA assays can be used to provide an accurate, reproducible, and quantitative measure of IgG and IgM aCL concentration in serum samples.
707 citations