scholarly journals OP0277 RNA SEQUENCING AND MACHINE LEARNING TECHNIQUES PREDICT MAJOR ORGAN INVOLVEMENT IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

2019 ◽  
Author(s):  
Anastasia Filia ◽  
George Bertsias ◽  
Nikolaos Panousis ◽  
Dionisis Nikolopoulos ◽  
Emmanouil Dermitzakis ◽  
...  
Keyword(s):  
Machine Learning ◽  
Systemic Lupus Erythematosus ◽  
Rna Sequencing ◽  
Lupus Erythematosus ◽  
Machine Learning Techniques ◽  
Organ Involvement ◽  
Systemic Lupus ◽  
Learning Techniques ◽  
Major Organ

scholarly journals Phenome-wide association study identifies dsDNA as a driver of major organ involvement in systemic lupus erythematosus

Lupus ◽  
2018 ◽  
Vol 28 (1) ◽  
pp. 66-76 ◽  
Author(s):  
A. Barnado ◽  
R.J. Carroll ◽  
C. Casey ◽  
L. Wheless ◽  
J.C. Denny ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Association Study ◽  
Lupus Erythematosus ◽  
Organ Involvement ◽  
Health Record ◽  
Systemic Lupus ◽  
False Discovery ◽  
Major Organ ◽  
Autoantibody Status ◽  
Dsdna Antibodies

In systemic lupus erythematosus (SLE), dsDNA antibodies are associated with renal disease. Less is known about comorbidities in patients without dsDNA or other autoantibodies. Using an electronic health record (EHR) SLE cohort, we employed a phenome-wide association study (PheWAS) that scans across billing codes to compare comorbidities in SLE patients with and without autoantibodies. We used our validated algorithm to identify SLE subjects. Autoantibody status was defined as ever positive for dsDNA, RNP, Smith, SSA and SSB. PheWAS was performed in antibody positive vs. negative SLE patients adjusting for age and race and using a false discovery rate of 0.05. We identified 1097 SLE subjects. In the PheWAS of dsDNA positive vs. negative subjects, dsDNA positive subjects were more likely to have nephritis ( p = 2.33 × 10−9) and renal failure ( p = 1.85 × 10−5). After adjusting for sex, race, age and other autoantibodies, dsDNA was independently associated with nephritis and chronic kidney disease. Those patients negative for dsDNA, RNP, SSA and SSB negative subjects were all more likely to have billing codes for sleep, pain and mood disorders. PheWAS uncovered a hierarchy within SLE-specific autoantibodies with dsDNA having the greatest impact on major organ involvement.

scholarly journals 86 Do all antiphospholipid antibodies confer the same risk for major organ involvement in systemic lupus erythematosus patients?

2019 ◽  
Author(s):  
Leyre Riancho-Zarrabeitia ◽  
Víctor M Martínez-Taboada ◽  
Iñigo Rua Figueroa ◽  
Fernando Alonso ◽  
Maria Galindo Izquierdo ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Antiphospholipid Antibodies ◽  
Organ Involvement ◽  
Systemic Lupus ◽  
Major Organ

scholarly journals Performance of 2019 EULAR/ACR Classification Criteria for Systemic Lupus Erythematosus in Children and Adults : A Retrospective Observational Study

2021 ◽  
Author(s):  
Sang Cheng ◽  
Huihua Ding ◽  
Haiyan Xue ◽  
Min Xia ◽  
Zhiqiang Tu ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
High Sensitivity ◽  
Classification Criteria ◽  
Organ Involvement ◽  
Lower Sensitivity ◽  
Systemic Lupus ◽  
American College Of Rheumatology ◽  
Major Organ ◽  
Increased Sensitivity

Abstract Background: The European League Against Rheumatism (EULAR) and American College of Rheumatology (ACR) recently developed a systemic lupus erythematosus (SLE) classification criteria (EULAR/ACR-2019) with high sensitivity and specificity. The aim of this study was to validate and compare the performance of the newly developed criteria to that of the ACR-1997 and the 2012 Systemic Lupus International Collaborating Clinics (SLICC-2012) criteria in juvenile-onset SLE (jSLE) and adult-onset SLE (aSLE) patients.Methods: We conducted a retrospective study of SLE patients (221 children and adult) and controls (214 children and adult) with defined rheumatic diseases to establish the ACR-1997, SLICC-2012 and EULAR/ACR-2019 criteria. The performance of the three criteria was statistically analyzed.Results: For jSLE, sensitivities of ACR-1997, SLICC-2012 and EULAR/ACR-2019 criteria were 63.3%, 94.6% and 98.2% (P < 0.001), with specificities 99.5%, 98.6% and 93.5% (P < 0.001), respectively. For aSLE, sensitivities of ACR-1997, SLICC-2012 and EULAR/ACR-2019 criteria were 72.9%, 96.8% and 99.1% (P < 0.001), with specificities 97.2%, 92.5% and 90.2% (P = 0.013), respectively. In ANA positive juvenile patients, a EULAR/ACR score ≥13 instead of a score ≥10 resulted in higher specificity (93.1% vs. 75.9%), despite slightly lower sensitivity (92.2% vs. 99.5%). In both jSLE and aSLE patients, the SLICC-2012 and EULAR/ACR-2019 criteria had increased sensitivity for major organ involvement than ACR-1997.Conclusion: The EULAR/ACR-2019 criteria showed similar sensitivity to jSLE and aSLE patients and was more sensitive than ACR-1997 and SLICC-2012 criteria, allowing earlier recognition of patients with single or major organ involvement. The adoption of a EULAR/ACR total score ≥13 in this study, instead of the initially proposed ≥10 score, was more appropriate to classify jSLE.

Structural and Neurochemical Markers of Brain Injury in the Migraine Diathesis of Systemic Lupus Erythematosus

Cephalalgia ◽  
1998 ◽  
Vol 18 (4) ◽  
pp. 209-215 ◽  
Author(s):  
CL Rozell ◽  
WL Sibbitt ◽  
WM Brooks
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Brain Injury ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Migraine Headache ◽  
Organ Involvement ◽  
Systemic Lupus ◽  
Recurrent Headache ◽  
Patients At Risk ◽  
Magnetic Resonance Imaging Mri

Objective: To determine whether migraine in systemic lupus erythematosus (SLE) is associated with accentuated brain injury and disease activity. Methods: Forty SLE patients (11 without headache, 11 with non-migraine headache, and 18 with migraine) underwent clinical evaluation, magnetic resonance imaging (MRI), and spectroscopy (MRS). Results: Recurrent headache occurred in 75% of SLE patients. MRI abnormalities and reduced N-acetylaspartate were common. However, migraine in SLE was not associated with increased disease activity or severity, neuropsychiatrie manifestations, or end-organ involvement compared to patients without migraine ( p>0.05). There were no differences in the prevalence or severity of MRI or MRS abnormalities between SLE patients with migraine, with non-migraine headache, or without headache ( p>0.05). Conclusions: Headache does not identify SLE patients at risk for brain injury, increased disease activity, or increased end-organ involvement. Aggressive immunosuppressive therapy for headache alone is not indicated in SLE.

Increased CD4+CD25-Foxp3+ T cells in Chinese systemic lupus erythematosus: correlate with disease activity and organ involvement

Lupus ◽  
2018 ◽  
Vol 27 (13) ◽  
pp. 2057-2068 ◽  
Author(s):  
Z-J Yin ◽  
B-M Ju ◽  
L Zhu ◽  
N Hu ◽  
J Luo ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Cell Subset ◽  
Treg Cells ◽  
Organ Involvement ◽  
Systemic Lupus ◽  
Clinical Indicators ◽  
Disease States

Objective The increment of CD4+CD25−Foxp3+T cells has been reported in systemic lupus erythematosus (SLE) patients. However, the exact identity of this T cell subset is still unclear. Thus, we analyzed CD4+CD25−Foxp3+T cells and Treg cells (CD4+CD25+Foxp3+ T cells) in a large sample of Chinese SLE patients in different disease states. Methods A total of 280 SLE patients and 38 healthy volunteers were enrolled, which included 21 patients with untreated new-onset lupus (UNOL), 13 patients with drug withdrawal more than 6 months and 246 patients with treatments. Phenotypic and functional analysis of peripheral blood CD4+CD25−Foxp3+ T cells and Treg cells were performed by flow cytometry. The correlation of CD4+CD25−Foxp3+T cells and Treg cells with disease activity, clinical indicators and organ involvement were analyzed. Results CD4+CD25−Foxp3+ T cells and Treg cells were significantly increased in SLE patients and showed significantly positive correlations with disease activity. CD4+CD25−Foxp3+ T cells were significantly increased in patients with skin and hematologic involvement as well as arthritis. Diverse changes between CD4+CD25−Foxp3+ T cells and Treg cells when faced with different medications, especially HCQ and MMF. CD4+CD25−Foxp3+ T cells expressed more IFN-γ and less CTLA-4 than CD4+CD25+Foxp3+ T cells, which were similar to CD4+CD25+Foxp3− T cells, and expressed similar IL-17, ICOS and Helios to CD4+CD25+Foxp3+ T cells. The synthesis capacity of IL-10 of CD4+CD25−Foxp3+ T cells and the expression of GITR on CD4+CD25−Foxp3+ T cells were between CD4+CD25+Foxp3+ and CD4+CD25+Foxp3− T cells. Conclusions Our results indicate that increased CD4+CD25−Foxp3+ T cells in lupus patients, which combined the features of suppression and pro-inflammatory, may serve as a biomarker for disease activity and organ involvement in SLE.

scholarly journals Risk Factors for Clinical Coronary Heart Disease in Systemic Lupus Erythematosus: The Lupus and Atherosclerosis Evaluation of Risk (LASER) Study

2009 ◽  
Vol 37 (2) ◽  
pp. 322-329 ◽  
Author(s):  
SAHENA HAQUE ◽  
CAROLINE GORDON ◽  
DAVID ISENBERG ◽  
ANISUR RAHMAN ◽  
PETER LANYON ◽  
...  
Keyword(s):  
Risk Factors ◽  
Systemic Lupus Erythematosus ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Lupus Erythematosus ◽  
Clinical Setting ◽  
Organ Involvement ◽  
Systemic Lupus ◽  
Chd Risk ◽  
Control Disease

Objective. Accelerated atherosclerosis and premature coronary heart disease (CHD) are recognized complications of systemic lupus erythematosus (SLE), but the exact etiology remains unclear and is likely to be multifactorial. We hypothesized that SLE patients with CHD have increased exposure to traditional risk factors as well as differing disease phenotype and therapy-related factors compared to SLE patients free of CHD. Our aim was to examine risk factors for development of clinical CHD in SLE in the clinical setting.Methods. In a UK-wide multicenter retrospective case-control study we recruited 53 SLE patients with verified clinical CHD (myocardial infarction or angina pectoris) and 96 SLE patients without clinical CHD. Controls were recruited from the same center as the case and matched by disease duration. Charts were reviewed up to time of event for cases, or the same “dummy-date” in controls.Results. SLE patients with clinical CHD were older at the time of event [mean (SD) 53 (10) vs 42 (10) yrs; p < 0.001], more likely to be male [11 (20%) vs 3 (7%); p < 0.001], and had more exposure to all classic CHD risk factors compared to SLE patients without clinical CHD. They were also more likely to have been treated with corticosteroids (OR 2.46; 95% CI 1.03, 5.88) and azathioprine (OR 2.33; 95% CI 1.16, 4.67) and to have evidence of damage on the pre-event SLICC damage index (SDI) (OR 2.20; 95% CI 1.09, 4.44). There was no difference between groups with regard to clinical organ involvement or autoantibody profile.Conclusion. Our study highlights the need for clinical vigilance to identify modifiable risk factors in the clinical setting and in particular with male patients. The pattern of organ involvement did not differ in SLE patients with CHD events. However, the higher pre-event SDI, azathioprine exposure, and pattern of damage items (disease-related rather than therapy-related) in cases suggests that a persistent active lupus phenotype contributes to CHD risk. In this regard, corticosteroids and azathioprine may not control disease well enough to prevent CHD. Clinical trials are needed to determine whether classic risk factor modification will have a role in primary prevention of CHD in SLE patients and whether new therapies that control disease activity can better reduce CHD risk.

scholarly journals Machine learning applied to whole-blood RNA-sequencing data uncovers distinct subsets of patients with systemic lupus erythematosus

2019 ◽  
Author(s):  
William A Figgett ◽  
Katherine Monaghan ◽  
Milica Ng ◽  
Monther Alhamdoosh ◽  
Eugene Maraskovsky ◽  
...  
Keyword(s):  
Gene Expression ◽  
Machine Learning ◽  
Systemic Lupus Erythematosus ◽  
Clinical Trials ◽  
Lupus Erythematosus ◽  
Whole Blood ◽  
Rna Seq ◽  
Systemic Lupus ◽  
Disease Heterogeneity ◽  
Healthy Donors

ABSTRACTObjectiveSystemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease that is difficult to treat. There is currently no optimal stratification of patients with SLE, and thus responses to available treatments are unpredictable. Here, we developed a new stratification scheme for patients with SLE, based on the whole-blood transcriptomes of patients with SLE.MethodsWe applied machine learning approaches to RNA-sequencing (RNA-seq) datasets to stratify patients with SLE into four distinct clusters based on their gene expression profiles. A meta-analysis on two recently published whole-blood RNA-seq datasets was carried out and an additional similar dataset of 30 patients with SLE and 29 healthy donors was contributed in this research; 141 patients with SLE and 51 healthy donors were analysed in total.ResultsExamination of SLE clusters, as opposed to unstratified SLE patients, revealed underappreciated differences in the pattern of expression of disease-related genes relative to clinical presentation. Moreover, gene signatures correlated to flare activity were successfully identified.ConclusionGiven that disease heterogeneity has confounded research studies and clinical trials, our approach addresses current unmet medical needs and provides a greater understanding of SLE heterogeneity in humans. Stratification of patients based on gene expression signatures may be a valuable strategy to harness disease heterogeneity and identify patient populations that may be at an increased risk of disease symptoms. Further, this approach can be used to understand the variability in responsiveness to therapeutics, thereby improving the design of clinical trials and advancing personalised therapy.

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