Cohort Of Systemic Lupus Erythematosus Patients Research Articles

The relation of CD4+CD25+Foxp3+ regulatory T cells concentration with disease activity and damage index in systemic lupus erythematosus.

Regulatory T cells (Treg) deficits, both quantitative and qualitative, are known to be possible triggers for the development of autoimmune disorders by causing T and B cells dysfunction. The contribution of Treg deficiency in the etiology of systemic lupus erythematosus (SLE) is still being debated. The aim of the present study is to evaluate the percentage of circulating CD4+CD25+Foxp3+ Treg cells in a cohort of Egyptian SLE patients and to correlate this value with the activity and damage index of these patients. 50 female patients with SLE together with an equal number of age- and sex-matched healthy controls were enrolled in the study. Flow cytometric determination of peripheral Treg cells was carried out for all participants by detecting the percentage of CD4+CD25+Foxp3+ cells to compare cases with the control group. Disease activity was assessed using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), while disease damage was assessed using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR DI). Both indices were correlated with the percentage of CD4+CD25+Foxp3 T regulatory cells. CD4+CD25+Foxp3+ Treg cells percentage was significantly decreased in patients with SLE as compared to healthy controls. On correlating CD4+CD25+Foxp3+ Treg percentage with SLEDAI-2K, a significantly negative correlation was found. Also, there was a negative significant correlation between CD4+CD25+Foxp3+ Treg cells percentage and SLICC/ACR DI. On correlating SLEDAI-2K with damage index (SLICC/ACR DI), we found highly significant positive correlation. Our study showed impaired production of CD4+CD25+Foxp3+ Tregs in SLE patients, which can play a reciprocal role with some cytokines to affect the activity of the disease and organ damage. CD4+CD25+Foxp3+ Tregs cells should be the target to determine the clinical effectiveness of new therapy to modulate Tregs besides the traditional treatments.

Elevated Detection of Dual Antibody B Cells Identifies Lupus Patients With B Cell-Reactive VH4-34 Autoantibodies.

About 5% of B cells in healthy mice and humans are allelically or isotypically included and hence co-express two different antibodies. In mice, dual antibody B cells (B2R) expand with systemic autoimmunity, co-express autoreactive and non-autoreactive antibodies, and participate in immune responses, but this phenomenon is strain dependent. This study was developed with two goals: 1) to establish the contribution of TLR and IFN receptor signaling to the development of germinal center B cells that express two antibodies in MRL/lpr mice; and 2) to determine whether B2R B cells are increased and particularly activated in a subset of adult patients diagnosed with systemic lupus erythematosus (SLE). Results from the MRL/lpr studies indicate that the enhanced differentiation of dual-κ B cells into germinal center B cells is due to a heightened response to TLR7 and TLR9 signaling, further fueled by an increased response to type II IFN. To understand the clinical and translational implications of our observations in mouse B2R B cells, cohorts of SLE patients and healthy controls were recruited and evaluated for expression of dual BCRs. Results from flow cytometry and microscopy revealed supraphysiological frequencies of κ+λ+ B2R cells in one fourth of the SLE patients. Abnormal numbers of κ+λ+ B cells correlated with higher frequencies of activated naïve B cells and age-associated B cells, and a lower proportion of “B cells that are naïve IgD+” (BND). However, results from single cell V(D)J sequencing demonstrated that these high κ+λ+ SLE patients harbored normal frequencies of κ+λ+ and other B2R B cells. and we further show that their B cells were instead decorated by κ and λ VH4-34 autoantibodies. Thus, our findings indicate that elevated flow cytometric detection of isotypically-included B cells can identify patients with high titers of B cell-reactive VH4-34 autoantibodies and abnormal distribution of B cell subsets relevant to autoimmunity.

Vitamin D levels in Greek patients with systemic lupus erythematosus.

Vitamin D deficiency has been observed in autoimmune rheumatic diseases, such as rheumatoid arthritis. The aim was to study vitamin D in patients with systemic lupus erythematosus (SLE) and its relationship with disease activity. In a cohort of 45 patients with SLE, 41 females and 4 males, aged 47.07 ± 2.17 years (mean ± SEM), and range = 21-79 years, 25(OH)D3 levels were determined by electrochemiluminescence. C3 and C4 levels were also analyzed. SLE disease activity was estimated by SLEDAI-2K. Observations were also performed in a control group matched for age and sex. In this cohort of SLE patients, 25(OH)D3 levels were 40.36 ± 2.41nmol/L (mean ± SEM) as opposed to 60.98 ± 4.28nmol/L in the control group (p < 0.001, Student's t test). Vitamin D levels were related to C3 (p < 0.001, linear regression analysis), correlation coefficient 0.106, r2 = 0.011, and C4 (p < 0.001); correlation coefficient 0.316 and r2 = 0.100; and inversely related to disease activity (p < 0.001), correlation coefficient -0.572 and r2 = 0.327. 25(OH)D3 levels were 17.73 ± 1.20nmol/L and 12.24 ± 0.93nmol/L, in the groups without and with renal involvement, respectively (p = 0.001, Student's t test). Vitamin D levels are low in SLE patients and are inversely related to disease activity. Routine screening for vitamin D levels should be performed in SLE patients.

Hydroxychloroquine use is not associated with QTc length in a large cohort of SLE and RA patients

BackgroundHydroxychloroquine (HCQ) is a cornerstone therapy for systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). However, reports of its use and subsequent fatal arrhythmias in patients with coronavirus disease 19 (COVID-19) have raised concern regarding its cardiovascular (CV) safety. Therefore, we examined the relationship between HCQ use and corrected QT (QTc) length in SLE and RA patients without clinical CV disease (CVD).MethodsSLE patients from the Columbia University Lupus Cohort registry (n = 352) and two RA cohorts (n = 178; ESCAPE-RA and RHYTHM-RA) with electrocardiograms (ECGs) collected as part of study data were analyzed. RA cohort participants were recruited from tertiary referral centers with additional referrals from community rheumatologists, while SLE subjects originated from the Columbia University Lupus Cohort. All patients met American College of Rheumatology (ACR) classification criteria for SLE or RA and lacked known CVD. The exposure of interest was HCQ use and main outcome measure was QTc length [continuous or categorical (≥ 440 ms and ≥ 500 ms)].ResultsOf the combined SLE and RA cohorts (n = 530), 70% were HCQ users and 44% had a QTc ≥ 440 ms. The adjusted mean QTc length was comparable between HCQ users vs non-users (438 ms vs 437 ms). In multivariable logistic models, HCQ use was not a significant predictor of a QTc ≥ 440 ms for the entire cohort (OR 0.77; 95% CI 0.48–1.23; p = 0.27). Importantly, a QTc ≥ 500 ms was inversely associated with HCQ use and not associated with arrhythmias or deaths. A significant interaction was found between HCQ use and use of anti-psychotics. Ultimately, the use of HCQ combined with any QTc prolonging medication as a group was associated with a QTc length (434 ms; 95% CI 430, 439) which was comparable to that of use of HCQ alone (433 ms; 95% CI 429-437).ConclusionIn a combined cohort of SLE and RA patients without clinical CVD, adjusted QTc length was comparable between HCQ and non-HCQ users, supporting its CV safety in patients with rheumatic diseases.

Systemic lupus erythematosus and pregnancy: A retrospective single-center study of 215 pregnancies from Portugal.

Systemic lupus erythematosus (SLE) is a life-threatening disorder that affects women at reproductive age. We evaluate the clinical impact of pregnancy in a cohort of Portuguese SLE patients and the risk factors associated with maternal and fetal adverse outcomes. A retrospective observational study that included all pregnant women with SLE managed at a Portuguese tertiary hospital, between January 1993 and December 2019. Baseline maternal information was collected, and maternal-fetal and neonatal outcomes were evaluated. Disease activity before and during pregnancy was assessed. We included 215 pregnancies from 143 patients. Lupus nephritis was present in 20.0% and antiphospholipid syndrome (APS) in 21.9% of the cases. Preconception consultation was performed in 86.9% of the pregnancies, and 92.5% of the patients had no or low disease activity at conception. During gestation, 79.6% of the patients were under treatment, and hydroxychloroquine (HCQ) was the most commonly used drug (63.7%). Low-dose acetylsalicylic acid (ASA) was prescribed at conception in 87.9% of the patients. The live birth rate was 84.2%. An adverse pregnancy outcome (APO) occurred in 41.4% of the pregnancies. A miscarriage rate of 15.3% and a preterm delivery rate of 15.4% were found. Preeclampsia and fetal growth restriction complicated 13.1% and 14.0% of the gestations, respectively. Neonatal lupus occurred in 7.1% of the newborns, and there were 2 cases of congenital heart block. Significant risk factors for the development of AOP were disease activity at conception, lupus flare, hypocomplementemia, positivity for lupus anticoagulant, and APS. The use of ASA was significantly associated with a reduced incidence of miscarriage. An SLE flare was diagnosed in 16.3% of the cases. We identified as risk factors for lupus flares the presence of active disease at conception, a previous history of lupus nephritis, and the use of chronic medication. HCQ use during pregnancy was associated with a significant reduction of flare incidence during pregnancy and postpartum. Pregnancy in an SLE patient is associated with an increased incidence of adverse obstetric outcomes. Good disease control before pregnancy and adequate treatment, especially with HCQ, is crucial to achieving the best obstetric results.

Association of TNFAIP3 gene polymorphism (rs5029939) with susceptibility and clinical phenotype of systemic lupus erythematosus.

Objectives This study aims to investigate the association of the tumor necrosis factor-alpha inducible protein 3 (TNFAIP3) (rs5029939) gene single nucleotide polymorphism (SNP) with the risk of systemic lupus erythematosus (SLE) and its clinical manifestations in a cohort of SLE patients.Patients and methods This study included a total of 180 participants (18 males, 72 females; mean age: 30.9±10.1 years; range 17 to 59 years) including 90 SLE patients and 90 healthy controls between March 2017 and February 2020. The TNFAIP3 rs5029939 gene polymorphism was identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in all participants.Results There was a significant difference in genotype distribution of the TNFAIP3 rs5029939 SNP between SLE patients and healthy controls, where CG genotype was more common in SLE patients (53.3%) than controls (11.1%) (p=0.001). We found a significant difference in G allele frequency of TNFAIP3 (rs5029939) (37.8% with SLE vs. 5.6% with controls, p=0.001). Genotype CG was significantly associated with lupus nephritis and neuropsychiatric manifestations (p<0.05). Although the response to treatment was numerically higher with the genotype CC, it did not reach statistical significance (p=0.4).Conclusion Our study suggests that TNFAIP3 rs5029939 gene polymorphism is associated with SLE susceptibility and may have an impact on its clinical phenotype. As such association differs among populations of diverse ethnic backgrounds, larger genome-wide association studies are warranted to further elucidate genetic associations.

Electroencephalographic Findings in a Cohort of Egyptian Systemic Lupus Erythematosus Patients with Neuropsychiatric Manifestations

Abstract Background and Objective Neuropsychiatric manifestations are frequently reported in 75% of Systemic Lupus Erythematosus (SLE) patients and that varied from mild subtle signs: headache or mood disturbance to life threatening conditions: acute confusional state, major fits, stroke or transverse myelitis. Electroencephalography (EEG) was used to determine whether there is a lateralized pattern of electrophysiologic dysfunction in SLE patients or not. So, this study was done to describe EEG findings in a cohort of Egyptian SLE patients with Neuropsychiatric SLE (NPSLE), its possible correlation with any of the disease activity parameters and comparing them to patients with Non-NPSLE. Patients and Methods This case-control study was conducted on 60 SLE patients who fulfilled the 2015 ACR/SLICC Classification Criteria for SLE. They were classified into 2 groups: 30 patients with NPSLE as cases and 30 patients without NPSLE (Non-NPSLE) as controls. All patients were subjected to detailed medical history taking together with full clinical examination and calculations of SLE disease activity using the SLE disease activity index (SLEDAI) score. Laboratory investigations including CBC, ESR, CRP, BUN, creatinine, urine analysis, P/C ratio, C3, C4, Lupus Anticoagulant (LAC) and Anticardiolipin (ACL) antibodies and EEG were done for all patients. MRI brain was done for patients with NPSLE. Results There were 6 neuropsychiatric manifestations in the NPSLE group; the commonest was seizure disorders (43.3%), followed by psychosis (20.0%), cerebrovascular disease (16.7%), acute confusional state (13.3%), headache (10.0%) and lastly demyelinating syndrome (6.7%). SLEDAI score was higher in NPSLE group (Median=16) than nonNPSLE group (Median=4) (P &amp;lt; 0.01). ACL IgM positivity was higher in NPSLE group (P &amp;lt; 0.05). 53.3% of NPSLE group had abnormal MRI brain findings, the most common finding was periventricular white matter lesion (23.3%), followed by infarction (13.3%), subcortical white matter lesion and demyelinating lesion (6.7%). Lastly was sinus thrombosis, cerebral edema and encephalomalacia (3.3% each). 12 patients out of 30 (40.0%) with NPSLE had EEG abnormalities, while all 30 patients with non-NPSLE had no EEG abnormalities. The most common EEG abnormalities in NPSLE group were diffuse slowing (20.0%), followed by generalized epileptiform activity (13.3%), and lastly temporal epileptiform activity (6.7% each). 50% of patients with abnormal EEG had normal MRI. 13 patients out of 30 with NPSLE had seizure disorders (43.3%), 8 of them had abnormal EEG (61.5%). Conclusion Not all patients with NPSLE must have abnormal brain MRI or EEG. EEG is a useful assistant tool in diagnosing and studying the different manifestations of NPSLE especially seizure disorder and acute confusional state, but it cannot be used as a screening test alone for detecting NPSLE and must be supplemented by neuroimaging studies.

Systemic Lupus Erythematosus and Pregnancy: a Portuguese Case-Control Study.

Pregnancy in systemic lupus erythematosus (SLE) patients is associated with an increased risk of adverse outcomes. During pregnancy, SLE patients have a higher rate of miscarriage, stillbirth, preterm delivery, fetal growth restriction, or hypertensive disorders of pregnancy. To date, only a few case-control studies were published with the purpose to evaluate the magnitude of risk associated with pregnancy in lupus patients. The aim of our study was to evaluate the maternal and fetal outcomes in a cohort of Portuguese SLE patients and to compare it with a group of healthy pregnant women. We conducted a retrospective case-control study that included all pregnant women with SLE managed at a Portuguese tertiary center, between 2010 and 2019. Pregnancy outcomes were compared between SLE patients and a group of matched healthy pregnant women. Baseline maternal data was collected, and maternal-fetal and neonatal outcomes were evaluated. One hundred twenty-four SLE pregnancies were included. Of the patients, 95.2% were in remission at conception. In 13.7% of cases, a lupus flare was diagnosed during gestation and in 17.9% in the postpartum period. The live birth rate was 84.6%, and the incidence of adverse outcomes was 40.3% (OR 2.64, 95% CI 1.67-4.18). Considering only patients in remission at conception, the presence of adverse outcomes remained significantly higher (36.8% vs. 20.3%, P< 0.01). Miscarriage rate was 15.3% (OR 5.85, 95% CI 2.57-13.34) and preterm delivery occurred in 12.4% of the patients (OR 1.72, 95% CI 0.83-3.57). Preeclampsia prevalence was higher in SLE patients (OR 3.92, 95% CI 1.32-11.57). In the SLE group, the newborn admission to an intensive care unit rate was increased (OR 4.99, 95% CI 1.47-16.90). No neonatal or maternal deaths were reported. In our study, pregnancy with SLE was associated with an increased incidence of adverse outcomes, even in a population of SLE patients with well-controlled disease.

Blood Genomics Identifies Three Subtypes of Systemic Lupus Erythematosus: "IFN-High," "NE-High," and "Mixed".

Purpose Systemic lupus erythematosus (SLE) is a systemic and multifactorial autoimmune disease, and its diverse clinical manifestations affect molecular diagnosis and drug benefits. Our study was aimed at defining the SLE subtypes based on blood transcriptome data, analyzing functional patterns, and elucidating drug benefits. Methods Three data sets were used in this paper that were collected from the Gene Expression Omnibus (GEO) database, which contained two published data sets of pediatric and adult SLE patients (GSE65391, GSE49454) and public longitudinal data (GSE72754) from a cohort of SLE patients treated with IFN-α Kinoid (IFN-K). Based on disease activity scores and gene expression data, we defined a global SLE signature and merged three clustering algorithms to develop a single-sample subtype classifier (SSC). Systematic analysis of coexpression networks based on modules revealed the molecular mechanism for each subtype. Results We identified 92 genes as a signature of the SLE subtypes and three intrinsic subsets (“IFN-high,” “NE-high,” and “mixed”), which varied in disease severity. We speculated that IFN-high might be due to the overproduction of interferons (IFNs) caused by viral infection, leading to the formation of autoantibodies. NE-high might primarily result from bacterial and fungal infections that stimulated neutrophils (NE) to produce neutrophil extracellular traps (NETs) and induced individual autoimmune responses. The mixed type contained both of these molecular mechanisms and showed an intrinsic connection. Conclusions Our research results indicated that identifying the molecular mechanism associated with different SLE subtypes would benefit the molecular diagnosis and stratified therapy. Moreover, repositioning of IFN-K based on subtypes also revealed an improved therapeutic effect, providing a new direction for disease treatment and drug development.

Forecasting index of unfavorable outcomes of systemic lupus erythematosus

The development of irreversible organ damage (IOD) in systemic lupus erythematosus (SLE) significantly increases the risk of death, worsens the quality of life and significantly increases the cost of treatment. The development and implementation of specific tools that will promote early identification of the risk of unfavorable outcomes is a priority. The article presents literature review on a new method for prediction of unfavorable outcomes in SLE – frailty index (FI, vulnerability index). FI, developed by a group of international experts on the basis of the database of the international cohort of SLE patients – SLICC (Systemic Lupus International Collaborating Clinics) – is easily reproducible in real clinical practice and can be used in patients with an early stage of SLE to predict the risk of death, the development of IOD. and hospitalization. The SLE Forecasting index of unfavorable outcomes (SLICC-FI) appears to be a promising clinical and research tool for identifying those who need more careful monitoring and an individual therapeutic strategy at an early stage of the disease.

Therapeutic potential of targeting Tfr/Tfh cell balance by low-dose-IL-2 in active SLE: a post hoc analysis from a double-blind RCT study

ObjectiveTo investigate the regulation of T follicular regulatory (Tfr) and T follicular (Tfh) cell subtypes by low-dose IL-2 in systemic lupus erythematosus (SLE) in a randomized, double-blind, placebo-controlled clinical trial.MethodsA post hoc analysis was performed in a randomized cohort of SLE patients (n=60) receiving low-dose IL-2 therapy (n=30) or placebo (n=30), along with the standard of care treatment. The primary endpoint was the attainment of SLE responder index-4 (SRI-4) at week 12 in the trial. Twenty-three healthy controls were enrolled for T cell subset detection at the same time as the trial. The t-stochastic neighbor embedding (tSNE) analysis of CD4 T subsets based on immune cells flow cytometry markers was performed to distinguish Tfh, Tfh1, Tfh2, Tfh17, and Tfr cell subsets.ResultsCompared with HC, the frequency of Tfr (CXCR5+PD-1low Treg and CXCR5+PD-1high Treg) cells was significantly reduced, while the pro-inflammatory Tfh cells were increased in patients with SLE. The imbalanced Tfh cell was associated with several pathogenic factors (anti-dsDNA antibodies (r=0.309, P=0.027) and serum IL-17 (r=0.328, P=0.021)) and SLE Disease Activity Index (SLEDAI) score (r=0.273, P=0.052). Decreased CXCR5+PD-1low Treg/Tfh and CXCR5+PD-1low Treg/Tfh17 were both associated with increased immunoglobulin M (IgM) (r=−0.448, P=0.002 and r=−0.336, P=0.024, respectively). Efficacy of low-dose IL-2 therapy was associated with a restored Tfr/Tfh cell balance.ConclusionThese data support the hypothesis that promotion of Tfr is associated with decreased disease activities and that low-dose IL-2 therapy can recover Tfr/Tfh immune balance.Trial registration numberClinicalTrials.gov Registries (NCT02465580).

Assessment of EULAR/ACR-2019, SLICC-2012 and ACR-1997 Classification Criteria in SLE with Longstanding Disease.

Background: Different classification criteria for systemic lupus erythematosus (SLE) have been launched over the years. Our aim was to evaluate the performance of the EULAR/ACR-2019, SLICC-2012 and ACR-1997 classification criteria in a cohort of SLE patients with longstanding disease. Methods: Descriptive observational study in 79 patients with established and longstanding SLE. The three classification criteria sets were applied to those patients. Results: Of the 79 patients, 70 were women (88.6%), with a mean age of 51.8 ± 14 years and a mean disease duration of 15.2 ± 11.5 years. The sensitivity of the different criteria were: 51.9%, 87.3% and 86.1% for ACR-1997, SLICC-2012 and EULAR/ACR-2019, respectively. In total, 68 out of 79 patients (53.7%) met all three classification criteria; 11.4% did not meet any classification criteria and were characterized by low SLEDAI (0.6 ± 0.9), low SLICC/ACR Damage Index (0.88 ± 0.56) and fulfilling only skin domains, antiphospholipid antibodies or hypocomplementemia. To fulfill EULAR/ACR-2019 criteria was associated with low complement levels (p < 0.04), high anti-dsDNA levels (p < 0.001), presence of lupus nephritis III-IV (p < 0.05) and arthritis (p < 0.001). Conclusion: The EULAR/ACR-2019 classification criteria showed high sensitivity, similar to SLICC-2012, in SLE patients with longstanding disease. Patients with serological, articular or renal involvement are more likely to fulfill SLICC-2012 or EULAR/ACR-2019 criteria.

POS0749 ASSOCIATION BETWEEN IMMUNE-SEROLOGICAL PROFILE AND PULMONARY MANIFESTATIONS IN COLOMBIAN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS (LES)

Background:Pulmonary involvement is common in Systemic Lupus Erythematosus (SLE) patients with varying degrees of parenchymal, vascular, and pleural compromise. In GLADEL, pulmonary involvement was reported in 28.4% of the cohort, but its occurrence ranges between 30-90% due to diversity in populations and the methods used to define it.Objectives:To describe the immune-serological profile of a Colombian cohort of SLE patients and to establish its association with pulmonary manifestations.Methods:Retrospective analysis of observational data from the follow-up of a cohort of adult patients with SLE. We included 559 patients that fulfilled the SLICC 2012 classification criteria with at least 6 months of disease history and being treated in a rheumatology specialized medical center between 2015 and 2018. The immuno-serological profile was characterized, and pulmonary involvement was monitored for 1 year. Diagnosis of pulmonary involvement was performed with the rheumatologist report in the clinical chart. Prevalence of pulmonary manifestations and immune-serological profile was determined, and logistic regression was performed afterward adjusted by age, sex, and level of education to establish the association between pulmonary manifestations and a positive auto-antibodies profile.Results:The median age of the cohort was 45 years, 96.5% were female. Pulmonary involvement was documented in 113 patients (20.5%) at the beginning of the study. Their frequency was: pleuritis (14.3%), lupus pneumonitis (3.6%), pulmonary hypertension (3.2%), interstitial lung disease (ILD) (2.3%), pulmonary embolism (2.3%), lung fibrosis (2.14%), alveolar hemorrhage (1.4%), shrinking lung (0.2%). At 1 year of follow up. there were no statistically significant differences in the frequency of pulmonary manifestations. As for the immune-serological profile, there were positive ANA in 92%, anti-dsDNA in 53.1%, anti-B2GP IgM 15.2%, anti- B2GP IgG in 17.2%, and ENA in 97.2%; as for the ENA 41.7% had positive anti-RNP, 40.2% anti-Ro, 36.4% anti-SM and 16.5% anti-La. Low complement levels was characterized as follows: C3 53.1% and C4 29.2%. In the logistic regression adjusted by age, sex and level of education, there was an association between anti-SM and pulmonary manifestations with an adjusted OR of 1.85; 95% CI 1.13-3.01.Conclusion:An association between anti-SM positivity and pleuro-pulmonary manifestations was found. In other cohorts with a greater size, anti-La and anti-RNP have been associated with pulmonary involvement (OR 2.51; 95% CI 1.39-4.57 and OR 1.32; 95% CI 1-1.75 respectively). Anti-RNP positivity has been associated in particular with ILD, pulmonary hypertension and shrinking lung. Although these manifestations prevalence was similar in our cohort, an association with this antibody was not found (OR 1.01, 95% CI: 0.2-4.9). This could be explained by the smaller sample size. As for anti-La positivity, its prevalence in our cohort was less than what was found in the GLADEL cohort (16.5% vs 24.3% respectively). It is possible that this could explain the poor association between anti-La positivity with the presence of pulmonary manifestations in our study compared with those of the GLADEL cohort. There are data that indicates that anti-SM and anti-RNP simultaneous positivity is related mainly to pleuritis OR 1.98 (95% CI: 1.31-3); and this kind of involvement was found to be more frequent in our study. Our results suggest an association between positive anti-SM and pulmonary manifestations in Colombian patients with SLE, pleuritis in particular.

Cross-sectional study of plasma Axl, ferritin, IGFBP4 and sTNFR2 as biomarkers of disease activity in childhood-onset SLE: A study of the Pediatric Nephrology Research Consortium.

To evaluate the performance of 4 plasma protein markers for detecting disease activity in childhood-onset systemic lupus erythematosus (SLE) patients. Eighty-three consecutive pediatric patients fulfilling ≥4 ACR criteria for SLE and twenty-five healthy controls were prospectively recruited for serological testing of 4 protein markers identified by antibody-coated microarray screen, namely Axl, ferritin, IGFBP4 and sTNFR2. SLE disease activity was assessed using SLEDAI-2000 score. Fifty-seven patients had clinically active SLE (SLEDAI score ≥4, or having a flare). The plasma concentrations of Axl and ferritin were significantly higher in patients with active SLE than inactive SLE. Plasma Axl levels were significantly higher in active renal versus active non-renal SLE patients. Levels of Axl, ferritin and IGFBP4 correlated significantly with SLEDAI scores. Levels of Axl, IFGBP4 and sTNFR2 inversely correlated with plasma complement C3 levels. Only plasma Axl and ferritin levels correlated with degree of proteinuria. These markers were more specific, but less sensitive, in detecting concurrent SLE activity than elevated anti-dsDNA antibody titer or decreased C3. Ferritin and IGFBP4 levels were more specific for concurrent active lupus nephritis than anti-dsDNA or C3. Plasma ferritin was the best monitor of global SLE activity, followed by C3 then Axl, while both Axl and C3 were best monitors of clinical lupus nephritis activity. In childhood-onset SLE patients, plasma ferritin and Axl perform better than traditional yardsticks in identifying disease activity, either global or renal. The performance of these plasma markers should be explored further in longitudinal cohorts of SLE patients.

P160 Clinical and sociodemographic associates of depression and anxiety in SLE

Abstract Background/Aims In our recent systematic review, we have shown a high prevalence for depression (35%) and anxiety (26%) in systemic lupus erythematosus (SLE) . A better understanding of the SLE phenotypic manifestations associated with depression and anxiety may lead to earlier diagnosis and treatment interventions. Our objective is to determine the overall prevalence of anxiety and depression in a cohort of SLE patients, stratified by SLE-implicated organ systems and to study their associations. Methods Patients attending the Toronto Lupus Clinic from August 2017 to January 2019 were studied. Depression and Anxiety were diagnosed with Centre for Epidemiological Studies-Depression Scale (cut-off26), BECK Depression Inventory-II (cut-off18), and the BECK Anxiety Inventory (cut-off19). Disease activity was measured with the SLE Disease Activity Index 2000 (SLEDAI-2K). SLE phenotypic manifestations were stratified based on the organ systems of cumulative 10-year SLEDAI-2K. Separate multivariate logistic regression analyses (for depression [D], anxiety [A], and co-morbid anxiety and depression [AD]) were performed to study the factors associated factors, including age at enrolment, sex, ethnicity, disease duration, inception status (enrolled in the clinic within 1 year of SLE diagnosis), fibromyalgia, and SLE phenotypic manifestations, comparing their significance to the group with neither A or D. Results 341 patients (89.7% female), with mean age 45.917.8 years were studied. The prevalence of A and D in the cohort was 34% and 27% respectively, while 21% of the total cohort was found to have AD. Among the 3 outcome groups, MSK system involvement has a significantly higher prevalence when compared to the group with neither A or D (p-values&amp;lt; 0.05). Skin system involvement was also significantly more prevalent among A, D, and AD groups, in comparison to the normal group. Patients with A had significantly higher odds of skin system involvement compared to the normal group (OR = 1.8; 95% CI: 1.1, 3.0). Patients with D had higher odds of MSK (OR = 1.9; 95% CI: 1.1, 3.5) and skin system involvement (OR = 1.8; 95% CI: 1.04, 3.2) compared to the group with neither A or D. Additionally, the odds of skin system involvement was significantly higher among patients with AD, compared to the group with neither (OR = 2.0, 95% CI: 1.2, 3.9). In all three models, employment and fibromyalgia were also significant. Age at enrolment was significant in the D and AD models, while inception patient status was significant in the D model exclusively. Conclusion SLE phenotypic manifestation, specifically those involving patients’ skin or MSK systems, along with fibromyalgia, socio-demographic factors, and inception status were associated with anxiety or depression. Routine patient screening and evaluation, especially among patients with shorter disease duration, for these associated factors may facilitate the diagnosis of these mental health disorders, and allow for more timely diagnosis and intervention strategies. Disclosure D.F. Eldeiry: None. M. Zandy: None. O.E. Tayer-Shifman: None. A. Kwan: None. S. Marzouk: None. J. Su: None. K. Bingham: None. Z. Touma: Grants/research support; Young operating and young investigator salary award of the Arthritis Society, new investigator research grant of Physicians' Services Inc Foundation, the CIORA, Rocca Family, Kaiser Family. Other; The Toronto Lupus Clinic Research Program is supported financially by the University Health Network, the Lou Rocca Family, and the Lupus Foundation of Ontario.

P164 Vitamin D receptor gene polymorphisms in a cohort of systemic lupus erythematosus patients in Malta

Abstract Background/Aims Vitamin D deficiency is highly prevalent in systemic lupus erythematosus (SLE) patients, most likely due to sun avoidance. Vitamin D acts through the vitamin D receptor (VDR) that is present in most cells, and it can regulate the transcription of over 200 genes. The expression of vitamin D receptors by a variety of cells belonging to the innate and adaptive immune systems has created interest with regards to the role of vitamin D in the pathogenesis of SLE. Several polymorphisms of the VDR gene have been described, namely Bsml (rs1544410), Apal (rs7975232), Taql(rs731236) and Fokl (rs2228570). A number of VDR gene polymorphisms have been associated with increased risk of SLE mostly in Asians and Africans. The aim of this study was to establish whether an association was present between VDR gene polymorphisms (Bsml, Apal, Taql and Fokl) and SLE susceptibility in a cohort of SLE patients living in Malta. Methods 63 SLE patients living in Malta and attending Rheumatology clinic at Mater Dei Hospital were recruited for the study after providing informed consent. The patients were over 18 years and fulfilled the SLICC classification criteria for SLE. Blood samples were taken from all the SLE patents. 93 cord blood samples obtained from individuals living in Malta were used as a control. DNA extraction was carried out from the blood samples. The VDR gene was screened and the regions containing the VDR polymorphisms were amplified for each patient. The amplified regions were then digested with their respective restriction enzymes in order to view the patient’s genotype via restriction fragment length polymorphism. Statistical analysis, including odds ratio (OR), was carried out to gauge the significance in the association of these polymorphisms with SLE. Results 93.7% of SLE patients were female and they had a mean age of 45.3 years. All the patients were of Caucasian ethnicity. 14.3% had vitamin D deficiency (serum 25-hydroxyvitamin D &amp;lt; 20ng/ml) and 25.4% were vitamin D insufficient (serum 25-hydroxyvitamin D 20-29ng/ml). The results showed that when Apa1 polymorphism was present as a homozygote for the variant allele (AA) there was a significant decrease in SLE prevalence (OR = 0.39, CI 0.17-0.87, p = 0.02). The results were also analysed by placing the polymorphs into haplotypes. The haplotype containing all wild-type alleles for the VDR gene and the haplotype containing all wild-type alleles with the variant allele for Fok1 had an increased prevalence of SLE by around 2 fold (OR = 1.95, CI 1.12-3.38, p = 0.01 and OR = 2.36, CI 1.13-4.91, p = 0.02 respectively). Conclusion The study showed that in the Maltese population the presence of the VDR gene polymorphism haplotype containing all wild-type alleles and the haplotype containing all wild-type alleles with the variant allele for Fok1 are associated with an increased risk of SLE. Disclosure J. Grech Meli: None. R. Magro: None. J. Debattista: None. N. Aquilina: None. K. Gatt: None. A.A. Borg: None. C. Scerri: None.

Prevalence and treatment conditions for hypertension and dyslipidaemia complicated with systemic lupus erythematosus: A multi-centre cross-sectional study.

This study aimed to assess the prevalence and actual treatment conditions for hypertension and dyslipidaemia complicated with systemic lupus erythematosus (SLE). This was a cross-sectional study. We established the lupus registry of nationwide institutions (LUNA), a multi-centre cohort of SLE patients in Japan. From February 2016 to July 2018, 597 SLE patients were registered in the LUNA. We evaluated the incidence of hypertension and dyslipidaemia and analysed the risk factors for hypertension and dyslipidaemia by logistic regression analysis. Overall, 597 patients were enrolled in the study. The median age was 44 years, and 88.0% of the patients were female. Among all the patients, 92.9% used prednisolone. The prevalence of hypertension and dyslipidaemia was 43.9% and 54.7%, respectively. Among the patients receiving medication for hypertension, 24.7% exhibited insufficient control (systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg), and among those receiving medication for hyperlipidaemia, 48.1% showed insufficient control (low-density lipoprotein cholesterol >140 mg/dL or triglyceride >150 mg/dL). The risk factors for hypertension were age, body mass index (BMI), disease duration, past maximum dose of prednisolone, and renal involvement, whereas those for dyslipidaemia were age and BMI. About half of the patients had hypertension or dyslipidaemia, and a considerable number of cases were poorly controlled despite medication. Our data suggest that physicians should treat SLE activity as well as its complications, especially the common risk factors for atherosclerosis.

MRNA expression analysis confirms CD44 splicing impairment in systemic lupus erythematosus patients.

Systemic Lupus Erythematosus (SLE) is a complex chronic autoimmune disease characterized by several immunological alterations. T cells have a peculiar role in SLE pathogenesis, moving from the bloodstream to the peripheral tissues, causing organ damage. This process is possible for their increased adherence and migration capacity mediated by adhesion molecules, such as CD44. Ten different variant isoforms of this molecule have been described, and two of them, CD44v3 and CD44v6 have been found to be increased on SLE T cells compared to healthy controls, being proposed as biomarkers of disease and disease activity. The process of alternative splicing of CD44 transcripts is not fully understood. We investigated the mRNA expression of CD44v3 and CD44v6 and also analyzed possible CD44 splicing regulators (ESRP1 molecule and rs9666607 CD44 polymorphism) in a cohort of SLE patients compared to healthy controls. This study involved 18 SLE patients and 18 healthy controls. Total RNA and DNA were extracted by peripheral blood mononuclear cells. The expression study was conducted by quantitative RT-polymerase chain reaction, using SYBR Green protocol. Genotyping of rs9666607 SNP was performed by direct sequencing. CD44v6 mRNA expression was higher in SLE patients compared to healthy controls (p = 0.028). CD44v3/v6 mRNA ratio in healthy controls was strongly unbalanced towards isoform v3 compared to SLE patients (p = 0.002) and decreased progressively from healthy controls to the SLE patients in remission and those with active disease (p = 0.015). The expression levels of CD44v3 and CD44v6 mRNA correlated with the disease duration (p = 0.038, Pearson r = 0.493 and p = 0.038, Pearson r = 0.495, respectively). Splicing regulator ESRP1 expression positively correlated with CD44v6 expression in healthy controls (p = 0.02, Pearson r = 0.532) but not in SLE patients. The variant A allele of rs9666607 of CD44 was associated with higher level of global CD44 mRNA (p = 0.04) but not with the variant isoforms. In SLE patients, the increase in CD44v6 protein correlates with a higher transcript level of this isoform, confirming an impairment of CD44 splicing in the disease, whose regulatory mechanisms require further investigation.

The impact of SARS-CoV-2 coronavirus infection in patients with systemic lupus erythematosus from a single center in Catalonia.

ObjectiveTo evaluate the incidence and characteristics of SARS-CoV-2 infection among patients with systemic lupus erythematosus (SLE) and to compare it to that described in the general population.MethodsFor 5 weeks, we carried out a cross-sectional study consisting of telephone interviews of SLE patients. We collected epidemiological data, symptoms suggesting COVID-19, results of nasopharyngeal swabs, and ongoing treatments. In those patients who required hospital admission, clinical, radiological, and laboratory features, and outcome were investigated.ResultsFour hundred patients with SLE completed the survey. Overall, 4 (1.00%, 95%CI 0.02–1.98) patients were classified as confirmed cases of COVID-19 and 26 (6.51%, 95%CI 4.08–8.94) as possible clinical cases. The incidence of confirmed cases in our series was similar to that of the Catalan population (1.00% versus 0.63%; p = 0.456), whereas the incidence of possible cases was higher in our series (6.51% versus 1.29%; p < 0.005). The only difference between SLE patients with confirmed and possible COVID-19 and those without was the percentage of patients who have had contact with a confirmed or possible case of COVID-19 (26.7% versus 9.2%; p = 0.003)ConclusionsThe incidence of COVID-19 in SLE patients with inactive disease is low and, in our series, all cases with confirmed infection recovered.Key Points• In a cohort of SLE patients with stable and clinical inactive disease, the incidence of COVID-19 is low.• All SLE patients with confirmed SARS-CoV-2 infection recovered.

Identification and stratification of systemic lupus erythematosus patients into two transcriptionally distinct clusters based on IFN-I signature.

Despite the significant advancement in the understanding of the pathophysiology of systemic lupus erythematosus (SLE) variable clinical response to newer therapies remain a major concern, especially for patients with lupus nephritis and neuropsychiatric systemic lupus erythematosus (NPSLE). We performed this study with an objective to comprehensively characterize Indian SLE patients with renal and neuropsychiatric manifestation with respect to their gene signature, cytokine profile and immune cell phenotypes. We characterized 68 Indian SLE subjects with diverse clinical profiles and disease activity and tried to identify differentially expressed genes and enriched pathways. To understand the temporal profile, same patients were followed at 6 and 12-months intervals. Additionally, auto-antibody profile, levels of various chemokines, cytokines and the proportion of different immune cells and their activation status were captured in these subjects. Multiple IFN-related pathways were enriched with significant increase in IFN-I gene signature in SLE patients as compared to normal healthy volunteers (NHV). We identified two transcriptionally distinct clusters within the same cohort of SLE patients with differential immune cell activation status, auto-antibody as well as plasma chemokines and cytokines profile. Identification of two distinct clusters of patients based on IFN-I signature provided new insights into the heterogeneity of underlying disease pathogenesis of Indian SLE cohort. Importantly, patient within those clusters retain their distinct expression dynamics of IFN-I signature over the time course of one year despite change in disease activity. This study will guide clinicians and researchers while designing future clinical trials on Indian SLE cohort.