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.

Clinical and immunological characteristics of 150 systemic lupus erythematosus patients in Jamaica: a comparative analysis

Lupus ◽  
2017 ◽  
Vol 26 (13) ◽  
pp. 1448-1456 ◽  
Author(s):  
K C Maloney ◽  
T S Ferguson ◽  
H D Stewart ◽  
A A Myers ◽  
K De Ceulaer
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Nephritis ◽  
Disease Activity ◽  
Renal Biopsy ◽  
Diagnostic Criteria ◽  
Lupus Erythematosus ◽  
Antinuclear Antibodies ◽  
Damage Index ◽  
Systemic Lupus ◽  
Dsdna Antibodies

Background Epidemiological studies in systemic lupus erythematosus have been reported in the literature in many countries and ethnic groups. Although systemic lupus erythematosus in Jamaica has been described in the past, there has not been a detailed evaluation of systemic lupus erythematosus patients in urban Jamaica, a largely Afro-Caribbean population. The goal of this study was to describe the clinical features, particularly disease activity, damage index and immunological features, of 150 systemic lupus erythematosus subjects. Methods 150 adult patients (≥18 years) followed in rheumatology clinic at a tertiary rheumatology hospital centre (one of two of the major public referral centres in Jamaica) and the private rheumatology offices in urban Jamaica who fulfilled Systemic Lupus International Collaborating Clinics (SLICC) criteria were included. Data were collected by detailed clinical interview and examination and laboratory investigations. Hence demographics, SLICC criteria, immunological profile, systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K) and SLICC/American College of Rheumatology (ACR) damage index (SDI) were documented. Results Of the 150 patients, 145 (96.7%) were female and five (3.3%) were male. The mean age at systemic lupus erythematosus onset was 33.2 ± 10.9. Mean disease duration was 11.3 ± 8.6 years. The most prevalent clinical SLICC criteria were musculoskeletal, with 141 (94%) of subjects experiencing arthralgia/arthritis, followed by mucocutaneous manifestations of alopecia 103 (68.7%) and malar rash 46 (30.7%), discoid rash 45 (30%) and photosensitivity 40 (26.7%). Lupus nephritis (biopsy proven) occurred in 42 (28%) subjects and 25 (16.7%) met SLICC diagnostic criteria with only positive antinuclear antibodies/dsDNA antibodies and lupus nephritis on renal biopsy. The most common laboratory SLICC criteria were positive antinuclear antibodies 136 (90.7%) followed by anti-dsDNA antibodies 95 (63.3%) and low complement (C3) levels 38 (25.3%). Twenty-seven (18%) met SLICC diagnostic criteria with only positive antinuclear antibodies/anti-dsDNA antibodies and lupus nephritis on renal biopsy. Mean SLEDAI score was 6.9 ± 5.1 with a range of 0–32. Organ damage occurred in 129 (86%) patients; mean SDI was 2.4 ± 1.8, with a range of 0–9. Conclusion These results are similar to the clinical manifestations reported in other Afro-Caribbean populations; however, distinct differences exist with respect to organ involvement and damage, particularly with respect to renal involvement, which appears to be reduced in our participants.

scholarly journals Systemic Lupus Erythematosus with and without Anti-dsDNA Antibodies: Analysis from a Large Monocentric Cohort

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Conti Fabrizio ◽  
Ceccarelli Fulvia ◽  
Perricone Carlo ◽  
Massaro Laura ◽  
Marocchi Elisa ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Clinical Laboratory ◽  
Renal Involvement ◽  
Serum Levels ◽  
Activity Measurement ◽  
Systemic Lupus ◽  
Before And After ◽  
Dsdna Antibodies

Objectives. The anti-dsDNA antibodies are a marker for Systemic Lupus Erythematosus (SLE) and 70–98% of patients test positive. We evaluated the demographic, clinical, laboratory, and therapeutical features of a monocentric SLE cohort according to the anti-dsDNA status.Methods. We identified three groups: anti-dsDNA + (persistent positivity); anti-dsDNA ± (initial positivity and subsequent negativity during disease course); anti-dsDNA − (persistent negativity). Disease activity was assessed by the European Consensus Lupus Activity Measurement (ECLAM).Results. We evaluated 393 patients (anti-dsDNA +: 62.3%; anti-dsDNA ±: 13.3%; anti-dsDNA −: 24.4%). The renal involvement was significantly more frequent in anti-dsDNA + (30.2%), compared with anti-dsDNA ± and anti-dsDNA − (21.1% and 18.7%, resp.;P=0.001). Serositis resulted significantly more frequent in anti-dsDNA − (82.3%) compared to anti-dsDNA + and anti-dsDNA ± (20.8% and 13.4%, resp.;P<0.0001). The reduction of C4 serum levels was identified significantly more frequently in anti-dsDNA + and anti-dsDNA ± (40.0% and 44.2%, resp.) compared with anti-dsDNA − (21.8%,P=0.005). We did not identify significant differences in the mean ECLAM values before and after modification of anti-dsDNA status (P=0.7).Conclusion. Anti-dsDNA status influences the clinical and immunological features of SLE patients. Nonetheless, it does not appear to affect disease activity.

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.

Sign in / Sign up

Export Citation Format

Share Document