Systemic Lupus Erythematosus Controls Research Articles

The Impact of the IL-10 Gene Polymorphism on mRNA Expression and IL-10 Serum Concentration in Polish Lupus Patients.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by the production of autoantibodies against a lot of nuclear components. Despite many studies on the genetic background of this disease, the pathogenesis remains unclear. The aim of the study is to comprehensively evaluate the polymorphism of the IL-10 promoter gene, its mRNA expression, and the serum IL-10 concentration of SLE female patients and females age-matched controls. Analyzing the association between the level of the tested cytokine and the polymorphism genotype-1082; -819; -592, we found statistically higher serum IL-10 levels in SLE patients compared to in healthy controls (11.9 ± 2.2 pg/mL vs. 9.4 ± 1.7 pg/mL, accordingly; p < 0.0001). We did not find statistically significant differences in the gene polymorphism of IL-10 among SLE patients and controls. The most significant observation derived from our study is that IL-10 mRNA transcripts are upregulated in SLE patients compared to in healthy controls (p < 0.0001). According to our results, the presence of the IL-10 genetic polymorphism has no clinical significance for the development of SLE, and subsequent differences in mRNA and IL-10 concentration results from the influence of other factors which should be the subject of further research.

Altered Arterial Stiffness, Ventricular-Arterial Coupling and Troponin Levels in Patients with Systemic Lupus Erythematosus.

Introduction: Systemic Lupus Erythematosus (SLE) is an autoimmune disease associated with an increased risk of cardiovascular diseases (CVDs), leading to elevated mortality rates among patients. We aimed to evaluate the levels of cardio-ankle vascular index (CAVI), global longitudinal strain (GLS), ventricular-arterial coupling (VAC), and high-sensitivity cardiac troponin I (hsTnI) in SLE patients and to explore their relationship with clinical parameters. Methods: This cross-sectional study enrolled 82 SLE patients without evident cardiac or kidney impairment and 41 age- and sex-matched healthy controls. We comparatively evaluated CAVI, GLS, VAC, and hsTnI between SLE patients and controls, and we assessed their association among SLE patients with disease activity based on the SELENA-SLEDAI Activity Index. Multivariate regression analysis was performed to identify independent predictors of CAVI and hsTnI within the SLE cohort. Results: In comparison to healthy controls, SLE patients presented with significantly higher CAVI, GLS, and hsTnI levels, while VAC was significantly reduced (p < 0.001). Furthermore, SLE patients with active disease (SELENA-SLEDAI ≥ 4) exhibited higher levels of CAVI and troponin than those with inactive disease (p < 0.001). SLEDAI was an independent predictor of CAVI, while VAC and SLEDAI were independent determinants of hsTnI in the SLE cohort. Conclusions: SLE patients displayed abnormal levels of CAVI, VAC, GLS, and troponin compared to healthy individuals. Our findings implicate the potential of those CV novel CVD risk factors to refine screening and therapeutic strategies for this specific population.

Single-cell transcriptomic analysis of hematopoietic progenitor cells from patients with systemic lupus erythematosus reveals interferon-inducible reprogramming in early progenitors.

Immune cells that contribute to the pathogenesis of systemic lupus erythematosus (SLE) derive from adult hematopoietic stem and progenitor cells (HSPCs) within the bone marrow (BM). For this reason, we reasoned that fundamental abnormalities in SLE can be traced to a BM-derived HSPC inflammatory signature. BM samples from four SLE patients, six healthy controls, and two umbilical cord blood (CB) samples were used. CD34+ cells were isolated from BM and CB samples, and single-cell RNA-sequencing was performed. A total of 426 cells and 24,473 genes were used in the analysis. Clustering analysis resulted in seven distinct clusters of cell types. Mutually exclusive markers, which were characteristic of each cell type, were identified. We identified three HSPC subpopulations, one of which consisted of proliferating cells (MKI67 expressing cells), one T-like, one B-like, and two myeloid-like progenitor subpopulations. Differential expression analysis revealed i) cell cycle-associated signatures, in healthy BM of HSPC clusters 3 and 4 when compared with CB, and ii) interferon (IFN) signatures in SLE BM of HSPC clusters 3 and 4 and myeloid-like progenitor cluster 5 when compared with healthy controls. The IFN signature in SLE appeared to be deregulated following TF regulatory network analysis and differential alternative splicing analysis between SLE and healthy controls in HSPC subpopulations. This study revealed both quantitative-as evidenced by decreased numbers of non-proliferating early progenitors-and qualitative differences-characterized by an IFN signature in SLE, which is known to drive loss of function and depletion of HSPCs. Chronic IFN exposure affects early hematopoietic progenitors in SLE, which may account for the immune aberrancies and the cytopenias in SLE.

Racial Differences in Plasma Microbial Translocation and Plasma Microbiome, Implications in Systemic Lupus Erythematosus Disease Pathogenesis.

Black groups have increased prevalence and accelerated pathogenicity of systemic lupus erythematosus (SLE) compared to other ethnic/racial groups. The microbiome and systemic microbial translocation are considered contributing factors to SLE disease pathogenesis. However, racial differences in the plasma microbiome and microbial translocation in lupus remain unknown. In the current study, we investigated plasma levels of microbial translocation (lipopolysaccharide [LPS] and zonulin) and the plasma microbiome using microbial 16S RNA sequencing of Black and White patients with SLE and Black and White healthy controls. Plasma microbial translocation was increased in Black patients versus in White patients and in patients with SLE versus healthy controls regardless of race. Compared to sex, age, and disease status, race had the strongest association with plasma microbiome differences. Black groups (Black controls and Black patients) had lower α-diversity than White groups (White controls and White patients) and more distinct β-diversity. Black and White patients demonstrated differences in plasma bacterial presence, including Staphylococcus and Burkholderia. Compared to White patients, Black patients had higher SLE Disease Activity Index (SLEDAI) scores and urinary protein levels as well as a trend for increased anti-double-stranded DNA (dsDNA) antibody levels consistent with the known increased severity of lupus in Black patients overall. Certain plasma bacteria at the genus level were identified that were associated with the SLEDAI score, urinary protein, and anti-dsDNA antibody levels. This study reveals racial differences in both quality and quantity of plasma microbial translocation and identified specific plasma microbiome differences associated with SLE disease pathogenesis. Thus, this study may provide new insights into future potential microbiome therapies on SLE pathogenesis.

Albumin to globulin ratio (AGR) in systemic lupus erythematosus: correlation with disease activity.

To investigate the role of albumin-to-globulin ratio (AGR) in systemic lupus erythematosus (SLE) and its relationship with disease activity. This retrospective study consecutively selected patients with SLE and healthy controls. Patients were divided into three groups according to the SLE Disease Activity Index 2000 (SLEDAI-2K): group 1 (mild disease activity, SLEDAI-2K ≤ 6), group 2 (moderate disease activity, SLEDAI-2K 7-12) and group 3 (severe disease activity, SLEDAI-2K > 12). Predictors of SLE disease activity were analysed by ordinal logistical regression. A total of 101 Chinese patients with SLE and 75 healthy Chinese controls were included. Patients with SLE had lower AGR values than healthy individuals, and group 3 patients with SLE displayed lower AGR values than those in group 1, but similar values to group 2. AGR was inversely correlated with SLEDAI-2K (r = -0.543). Ordinal logistic regression analysis showed that lower AGR (β = -1.319) and lower complement C4 (β = -1.073) were independent risk factors for SLE disease activity. AGR was decreased in patients with SLE and may be utilized as a useful inflammatory biomarker for monitoring SLE disease activity.

Continuous Unilateral Cephalalgia Due to Systemic Lupus Erythematosus: A Case Report

BackgroundHemicrania continua is a rare form of cephalalgia featuring a chronic and persistent headache in only one side of the head.ObjectivesIn this report, we present a case of a patient with hemicrania continua and systemic lupus erythematosus (SLE).MethodsWe collected patient data through the electronic medical record. Afterward, we reviewed the literature regarding hemicrania continua and its pathophysiology and correlation with neurovascular alterations, inflammation, and SLE.ResultsA 42-year-old woman visited the emergency department due to worsening constant unilateral cephalalgia that had been present for the past 6 months. The patient reported a highly intense (10/10) headache in the entire left hemicrania that radiated to the left shoulder. During physical examination, she presented with nystagmus, vertigo, and aggravated cephalalgia associated to body movement and, despite having no optic nerve thickening. In addition, she had jaundice, tachycardia, and splenomegaly. Complimentary exams found deep anemia, depletion in complement system and anti-nuclear factors, suggesting a possible hemolytic anemia (AIHA) due to SLE. Treatment was initiated with hydrocortisone and prednisone, associated with amitriptyline, fluoxetine and diazepam, reaching full remission. These syndromes have aggravated each other, and possibly the explanation for the cephalalgia remission was the control of AIHA and SLE. It features a rare case in literature and thus warrants discussion.

Screening of Environmental Chemicals to Characterize Exposures in Participants With Systemic Lupus Erythematosus.

There is a need to characterize exposures associated with the pathogenesis of systemic lupus erythematosus (SLE). In this pilot study, we explore a hypothesis-free approach that can measure thousands of exogenous chemicals in blood ("exposome") in patients with SLE and unaffected controls. This cross-sectional study analyzed a cohort of patients with prevalent SLE (n=285) and controls (n=106). Plasma was analyzed by liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF/MS). Mass spectrometry features present in at least 25% of all samples were selected for association analysis (n=2,737). Features were matched to potential chemicals using available databases. Association analysis of abundances of features with SLE status was performed, adjusting for age and sex. We also explored features associated with SLE phenotypes, sociodemographic factors, and current medication use. We found 30 features significantly associated with SLE status (Bonferroni P < 0.05). Of these, seven matched chemical names based on databases. These seven features included phthalate metabolites, a formetanate metabolite, and eugenol. The abundance of acid pesticides differed between patients with SLE and controls (Bonferroni P < 0.05). Two unmatched features were associated with a history of lupus nephritis, and one with anti-double-stranded DNA antibody production (Bonferroni P < 0.05). Seventeen features varied by self-reported race and ethnicity, including a polyfluoroalkyl substance (analysis of variance P < 1.69 × 10-5 ). Eleven features correlated with antimalarials, 6 with mycophenolate mofetil, and 29 with prednisone use. This proof-of-concept study demonstrates that LC-QTOF/MS is a powerful tool that agnostically detects circulating exogenous compounds. These analyses can generate hypotheses of disease-related exposures for future prospective, longitudinal studies.

Identification of new risk factors for hydroxychloroquine and chloroquine retinopathy in systemic lupus erythematosus patients

BackgroundLong-term hydroxychloroquine (HCQ) or chloroquine (CQ) intake causes retinal toxicity in 0.3–8 % of patients with rheumatic diseases. Numerous risk factors have been described, eg, daily dose by weight, treatment duration, chronic kidney disease, concurrent tamoxifen therapy and pre-existing retinal or macular disease. However, those factors cannot explain the entire risk of developing antimalarial retinopathy. ObjectiveThis study was undertaken to identify new risk factors associated with HCQ or CQ retinopathy (QRNP) in systemic lupus erythematosus (SLE) patients. MethodsThis case–control (1:2) study compared SLE patients with QRNP (cases) to those without (controls). Controls were matched for sex and known QRNP risk factors: HCQ and/or CQ treatment duration (±1 year) and age (±5 year) at SLE diagnosis. ResultsForty-eight cases were compared to 96 SLE controls. Multivariable logistic-regression analysis retained the following as independent determinants significantly associated with QRNP: concomitant selective serotonin-reuptake inhibitor (SSRI) or serotonin- and norepinephrine-reuptake inhibitor (SNRI) intake (OR [95 % confidence interval] 6.6 [1.2 to 40.9]; p < 0.01); antiphospholipid syndrome (OR=8.9 [2.2 to 41.4] p < 0.01); blood hydroxychloroquine/desethylchloroquine concentration ([HCQ]/[DCQ]) ratio <7.2 (OR 8.4 [2.7 to 30.8]; p < 0.01) or skin phototype ≥4 (OR 5.5 [1.4 to 26.5]; p = 0.02), but not daily HCQ dose, blood [HCQ] or body mass index. ConclusionThe results of this case–control study identified blood [HCQ]/[DCQ] ratio, concurrent SSRI/SNRI therapy, skin phototype ≥4 and antiphospholipid syndrome as new risk factors for QRNP.

A survey of ficolin-3 activity in Systemic Lupus Erythematosus reveals a link to hematological disease manifestations and autoantibody profile

The complement system plays a central role in the pathogenesis of Systemic Lupus Erythematosus (SLE), but most studies have focused on the classical pathway. Ficolin-3 is the main initiator of the lectin pathway of complement in humans, but its role in systemic autoimmune disease has not been conclusively determined. Here, we combined biochemical and genetic approaches to assess the contribution of ficolin-3 to SLE risk and disease manifestations. Ficolin-3 activity was measured by a functional assay in serum or plasma samples from Swedish SLE patients (n = 786) and controls matched for age and sex (n = 566). Genetic variants in an extended 300 kb genomic region spanning the FCN3 locus were analyzed for their association with ficolin-3 activity and SLE manifestations in a Swedish multicenter cohort (n = 985). Patients with ficolin-3 activity in the highest tertile showed a strong enrichment in an SLE cluster defined by anti-Sm/DNA/nucleosome antibodies (OR 3.0, p < 0.001) and had increased rates of hematological disease (OR 1.4, p = 0.078) and lymphopenia (OR = 1.6, p = 0.039). Genetic variants associated with low ficolin-3 activity mapped to an extended haplotype in high linkage disequilibrium upstream of the FCN3 gene. Patients carrying the lead genetic variant associated with low ficolin-3 activity had a lower frequency of hematological disease (OR 0.67, p = 0.018) and lymphopenia (OR 0.63, p = 0.031) and fewer autoantibodies (p = 0.0019). Loss-of-function variants in the FCN3 gene were not associated with SLE, but four (0.5 %) SLE patients developed acquired ficolin-3 deficiency where ficolin-3 activity in serum was depleted following diagnosis of SLE.Taken together, our results provide genetic and biochemical evidence that implicate the lectin pathway in hematological SLE manifestations. We also identify lectin pathway activation through ficolin-3 as a factor that contributes to the autoantibody response in SLE.

Increased cardiovascular risk in Korean patients with systemic lupus erythematosus: a population-based cohort study

To determine the increased risk of major adverse cardiovascular events (MACE) in patients with systemic lupus erythematosus (SLE) compared to the general population in Korea. Using data from the National Health Insurance Service database spanning 2008 to 2018, incident SLE patients aged 18 years and above were selected along with a 1:4 age- and sex-matched control group. The crude incidence rate (IR) of MACE was calculated as the number of events per 1000 person-years and the IR ratio (IRR) for MACE was adjusted using generalized estimating equations. Subgroup analysis was conducted to evaluate the risk differences of overall MACE and its composites based on age and sex stratification. The study included 8568 SLE patients and 34,272 controls. The cumulative IR of MACE per 1000 person-years in SLE patients and controls were 4.08 and 1.30, respectively. After adjusting for confounders, SLE patients had a higher risk of MACE compared to the general population (adjusted IRR of 2.40 [95% confidence interval [CI] 1.88–3.05]), with no gender differences observed. The increased risk of MACE in SLE patients was highest in the 18–39 age group (IRR 11.70, 95% CI 5.95–23.01) and gradually decreased with age. The increased risk of ischemic stroke (IRR 2.41, 95% CI 1.84–3.15) and myocardial infarction (IRR 2.19, 95% CI 1.30–3.68) in SLE patients was comparable. The risk of MACE in SLE patients is 2.40 times higher than that of the general population, with a higher relative risk observed in younger individuals.

Platelet-to-lymphocyte ratio as a biomarker of systemic inflammation in systemic lupus erythematosus: A meta-analysis and systematic review.

The objective of this study was to evaluate the relationship between the platelet-to-lymphocyte ratio (PLR) and systemic lupus erythematosus (SLE). Additionally, the study aimed to establish an association between PLR and SLE disease activity, specifically lupus nephritis (LN). We conducted a comprehensive search across Medline, Embase, and Cochrane databases to identify relevant articles. Subsequently, we performed meta-analyses to compare PLR between SLE patients and controls, as well as active and inactive SLE cases, along with LN and non-LN groups. Furthermore, a meta-analysis was conducted on correlation coefficients between PLR and various parameters in SLE patients, including the SLE Disease Activity Index (SLEDAI), C3, C4, anti-dsDNA, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). In total, fifteen studies comprising 1,522 SLE patients and 1,424 controls were eligible for inclusion. The meta-analysis demonstrated a significant elevation of PLR in the SLE group compared to the control group (Standardized Mean Difference [SMD] = 0.604, 95% Confidence Interval [CI] = 0.299-0.909, p < 0.001). Upon stratification by ethnicity, an elevated PLR was observed in the SLE group among both Asian and Arab populations. Subgroup analysis based on sample size revealed consistently higher PLR in both small (n < 200) and large sample (n ≥ 200) SLE groups. Moreover, when considering disease activity, there was a noteworthy trend of increased PLR in the active disease group compared to the inactive group (SMD = 0.553, 95% CI = 0.000-1.106, p = 0.050). However, the meta-analysis did not demonstrate a significant distinction in PLR between the LN and non-LN groups. Notably, a positive association was established between PLR and SLEDAI (correlation coefficient = 0.325, 95% CI = 0.176-0.459, p < 0.001). Furthermore, PLR exhibited positive correlations with ESR, CRP, proteinuria, C3, and anti-dsDNA antibody levels. The outcomes of this meta-analysis underscored the elevated PLR in SLE patients, suggesting its potential as a biomarker for gauging systemic inflammation in SLE. Additionally, PLR exhibited correlations with SLEDAI, as well as with key indicators such as ESR, CRP, proteinuria, C3, and anti-dsDNA antibody levels.

Type I Interferons induce endothelial destabilization in Systemic Lupus Erythematosus in a Tie2-dependent manner.

Endothelial cell (EC) dysfunction is a hallmark of Systemic Lupus Erythematosus (SLE) and Tie2 is a receptor essential for vascular stability. Inflammatory processes promote inhibition of Tie2 homeostatic activation, driving vascular dysfunction. In this work we determined whether type I Interferons (IFN) induce Tie2 signalling-mediated endothelial dysfunction in patients with SLE. Serum levels of Angiopoietin (Ang)-1, Ang-2 and soluble (s)Tie1 in patients with SLE and healthy controls were measured by ELISA. Monocytes from patients with SLE and Human Umbilical Vein EC (HUVEC) were stimulated with IFN-α, IFN-β (1000 I.U.) or SLE serum (20%). mRNA and protein expression, phosphorylation and translocation were determined by quantitative PCR, ELISA, Western Blot, flow cytometry and confocal microscopy. Viability and angiogenic capacity were determined by calcein and tube formation assays. We found that sTie1 and Ang-2 serum levels were increased and Ang-1 decreased in patients with SLE and were associated with clinical characteristics. Type I IFN significantly decreased Ang-1 and increased Ang-2 in monocytes from patients with SLE. Type I IFN increased sTie1 and Ang-2 secretion and reduced Tie2 activation in HUVEC. Functionally, type I IFN significantly reduced EC viability and impaired angiogenesis in a Tie2 signalling-dependent manner. Finally, SLE serum increased Ang-2 and sTie1 secretion and significantly decreased tube formation. Importantly, Tie1 and IFNAR1 knockdown reversed these effects in tube formation. Overall, type I IFN play an important role in the stability of EC by inhibiting Tie2 signalling, suggesting that these processes may be implicated in the cardiovascular events observed in patients with SLE.

Single-cell resolution of longitudinal blood transcriptome profiles in rheumatoid arthritis, systemic lupus erythematosus and healthy control pregnancies

ObjectivesComparative longitudinal analyses of cellular composition and peripheral blood gene expression in Rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and healthy pregnancies.MethodsIn total, 335 whole blood samples from 84 RA,...

Effect of SARS-CoV2 infection on disease flares in patients with systemic lupus erythematosus: a case-control study

Abstract Objectives To study the effect of SARS-CoV2 infection on flares of systemic lupus erythematosus (SLE). Methods Patients who fulfilled the ACR/SLICC criteria for SLE and had documented COVID-19 between February and November 2022 were identified retrospectively from our hospital COVID-19 registry. SLE controls who did not have SARS-CoV2 infection were randomly matched for age, sex and the time of infection in a 2:1 ratio with those infected. The primary outcome of interest was clinical flare of SLE within 90 days of COVID-19. The rate of SLE flares (mild/moderate or severe) was compared between SARS-CoV2-infected SLE patients and controls. Results 91 SLE patients with COVID-19 (age 48.6 ± 14.0 years; 95.6% women) and 182 SLE controls (age 48.7 ± 13.8 years; 95.6% women) were studied. Eleven of 91 (12.1%) SARS-CoV2-infected patients had serious manifestations. One (1.1%) patient died and 7(7.7%) developed severe complications. Within 90 days of SARS-CoV2 infection, 14(15.4%) patients developed mild/moderate clinical SLE flares and 2(2.2%) patients had severe SLE flares. The incidence of SLE flares in SARS-CoV2-infected patients was significantly higher than those without the infection (17.6% vs 5.5%; odds ratio 3.67[1.59–8.46]; p = 0.001). The changes in anti-dsDNA and complement levels, however, were not significantly different between the two groups. Among SARS-CoV2-infected SLE patients, those with clinical SLE flares had significantly lower C3 values (p = 0.004) before the infection than those without. Conclusion Clinical flares within 90 days were significantly more common in SLE patients infected with SARS-CoV2 than matched non-infected SLE controls.

Circulating lymphocyte subpopulations in patients with systemic lupus erythematosus and their correlation with disease activity.

The aim of the present study was to evaluate the overall alterations of peripheral blood lymphocyte subsets in patients with systemic lupus erythematosus (SLE). A total of 120 patients diagnosed with SLE and 64 health donors were enrolled. The lymphocyte subsets were detected using flow cytometry. Then the changes of lymphocyte subsets in patients and their correlation with disease activity were investigated. Compared with healthy controls, the counts of lymphocytes, T cells, B cells and NK cells in SLE patients were significantly decreased. Further analysis of T cells subpopulations revealed that the decrease in T cells counts in SLE patients was mainly attributed to a sharp decrease in CD4 + T cells counts. Meanwhile, there was a positive correlation between CD4 + T cells counts and serum complement 3 levels, and patients with lower CD4 + T cells counts had higher SLEDAI score. The counts of CD8 + T cells were comparable between SLE patients and controls, while the proportion of CD8 + T cells and cytotoxic T cells (CD8 + CD28 +) was prominently higher in SLE patients. Besides, the expression of HLA-DR on the surface of T and NK cells was significantly upregulated in SLE patients. Circulating lymphocyte subsets of SLE patients were seriously dysregulated, characterized by a decrease in CD4 + T cells and NK cells, as well as an increase in the proportion of activated T and NK cells. Reduction in CD4 + T cells in SLE patients was highly consistent with disease activity, indicating the crucial role of CD4 + T cells in the onset and progression of SLE.

Impact of belimumab therapy on the quality of life in patients with systemic lupus erythematosus: A cohort study.

Systemic lupus erythematosus (SLE) is a chronic and extremely disabling connective-tissue autoimmune disease with a tremendous impact on the quality of life (QoL). Belimumab, a B-lymphocyte-stimulator-specific inhibitor, is the first biologic drug approved as add-on therapy in patients with active, refractory auto-antibody-positive SLE.The impact of belimumab on the QoL of SLE patients was evaluated using a generic questionnaire short-form health survey 36 (SF-36) and the disease-specific questionnaire SLE-specific quality of life (SLEQoL).The Italian version of the SLEQoL and the SF-36 were administered to 46 SLE patients before and after 6months of belimumab therapy. The control population consisted of 40 age-matched healthy individuals. The questionnaires were completed before and after belimumab treatment and the results were compared using the Wilcoxon signed-rank test. In addition, data from healthy controls and SLE patients were compared using the Mann-Whitney test. Dichotomous variables were compared using Fisher's exact test.For SLE patients, the addition of belimumab to their therapeutic regimen significantly improved their health-related QoL (HRQoL), according to the results of the SF-36 and SLEQoL. The comparison of the data obtained before and after belimumab treatment showed a decrease in all six SLEQoL domains and an increase in all eight SF-36 domains. Moreover, treatment led to a reduction in the median prednisone dose, to 0mg/day (IQR 0-4.5mg/day). Before belimumab therapy, SLE patients had a worse HRQoL than the control group, based on both questionnaires, but after belimumab treatment the outcome scores between SLE patients and controls were similar, suggesting that belimumab therapy resulted in a strong improvement in HRQoL. These findings were supported by a decrease in the SELENA-SLEDAI score, a measure of disease activity.In addition to clinical remission and low disease activity, the goals of an innovative therapeutic strategy for SLE should include the attainment of a good HRQoL. Our study demonstrates that the combined use of the SF-36 and SLEQoL questionnaires can provide clinicians with a better understanding of the HRQoL of SLE patients.

Identification and Characterization of CD8+ CD27+ CXCR3- T Cell Dysregulation and Progression-Associated Biomarkers in Systemic Lupus Erythematosus.

Systemic Lupus Erythematosus (SLE) etiopathogenesis highlights the contributions of overproduction of CD4+ T cells and loss of immune tolerance. However, the involvement of CD8+ T cells in SLE pathology and disease progression remains unclear. Here, the comprehensive immune cell dysregulation in total 263 clinical peripheral blood samples composed of active SLE (aSLE), remission SLE (rSLE) and healthy controls (HCs) is investigated via mass cytometry, flow cytometry and single-cell RNA sequencing. This is observed that CD8+ CD27+ CXCR3- T cells are increased in rSLE compare to aSLE. Meanwhile, the effector function of CD8+ CD27+ CXCR3- T cells are overactive in aSLE compare to HCs and rSLE, and are positively associated with clinical SLE activity. In addition, the response of peripheral blood mononuclear cells (PBMCs) is monitored to interleukin-2 stimulation in aSLE and rSLE to construct dynamic network biomarker (DNB) model. It is demonstrated that DNB score-related parameters can faithfully predict the remission of aSLE and the flares of rSLE. The abundance and functional dysregulation of CD8+ CD27+ CXCR3- T cells can be potential biomarkers for SLE prognosis and concomitant diagnosis. The DNB score with accurate prediction to SLE disease progression can provide clinical treatment suggestions especially for drug dosage determination.

Increased carotid intima–media thickening and antioxidized low-density lipoprotein in an anti-Ro60 SLE autoantibody subset

ObjectivePremature atherosclerosis is associated with systemic lupus erythematosus (SLE). We have previously shown an association of anti-Ro60/La/Ro52 with antioxidized low-density lipoprotein (LDL) in SLE. Here, we hypothesized that carotid intima–media thickening (CIMT) would be associated with antioxidized LDL (anti-oxLDL)/antilipoprotein lipase (ALPL) in a specific SLE autoantibody subset (anti-Ro60 positive, anti-RNP positive, anti-SmRNP positive, or extractable nuclear antigen antibody negative).MethodsWe carried out a case-control study (one time-point testing) of CIMT, ALPL, anti-oxLDL, anti-low density lipoprotein (ALDL), and anti-LDL in 114 SLE patients and 117 age/sex-matched controls. The levels of total cholesterol, LDL, high-density lipoprotein (HDL), triglycerides, and HDL-Trig were also measured. A student's t-test was used for statistical analysis.ResultsInterestingly, the level of CIMT was highest in the SLE subset with anti-Ro60 (23/114). CIMT and anti-oxLDL were statistically significantly elevated in the anti-Ro60 SLE subset (1.3 ± 1.66, p &amp;lt; 0.01; 0.26 ± 0.16, p &amp;lt; 0.002, respectively) compared with controls (0.54 ± 1.26; 0.165 ± 0.13, respectively), but not anti-LPL/anti-LDL. CIMT was significantly elevated (0.9 ± 1.71; p &amp;lt; 0.05) in the SLE subset without antiextractable nuclear antigen (ENA) (63/114) compared with controls. The other antibodies in this subset were not statistically different from other SLE subsets or controls. Only antioxLDL was significantly elevated (0.29 ± 0.27; p &amp;lt; 0.005) in the SLE subset with anti-RNP (14/114) compared with controls, while none were elevated in the anti-SmRNP subset (6/114). We did not find any significant differences in lipids between the various SLE subsets.ConclusionCIMT segregates in anti-Ro and ENA negative groups either with or without anti-oxLDL. It will be clinically important if cardiovascular events are augmented in the SLE anti-Ro subset having elevated antioxidized LDL antibodies.

Lupus and HELLP Syndrome: case report

Introduction: Systemic Lupus Erythematosus (SLE) is a chronic autoimmune inflammatory disease that affects several organs and systems. This disease increases the risk of gestational hypertensive syndromes, which are clinical conditions characterized by increased blood pressure and maternal-fetal complications, including pre-eclampsia and HELLP syndrome. Case description: Twenty-four-year-old female patient, in her first pregnancy, with a diagnosis of SLE prior to pregnancy, which progressed to severe pre-eclampsia and HELLP. Discussion: Pregnant women with lupus gain greater relevance for presenting a wide variety of outcomes, from activation of the autoimmune disease, remission or even to remain unchanged throughout pregnancy. Furthermore, greater care is essential during pregnancy due to the complications that lupus can cause, such as Pre-Eclampsia and HELLP Syndrome. In short, it is certain that, when the disease is active, it can be associated with: prematurity; fetal growth restriction; preeclampsia and eclampsia; increased risk of thrombosis, infection, thrombocytopenia and postpartum hemorrhage. Conclusion: Such clinical complications show the importance of strict control of SLE, before and during pregnancy, in order to avoid complications. Considering the importance of this topic in public health, this case is extremely relevant for the education of women with SLE, in order to promote a correct therapy before and during pregnancy through prenatal care, to avoid the evolution to this very serious pathology.

Ancestry-based differences in the immune phenotype are associated with lupus activity.

Systemic lupus erythematosus (SLE) affects 1 in 537 Black women, which is >2-fold more than White women. Black patients develop the disease at a younger age, have more severe symptoms, and have a greater chance of early mortality. We used a multiomics approach to uncover ancestry-associated immune alterations in patients with SLE and healthy controls that may contribute biologically to disease disparities. Cell composition, signaling, epigenetics, and proteomics were evaluated by mass cytometry; droplet-based single-cell transcriptomics and proteomics; and bead-based multiplex soluble mediator levels in plasma. We observed altered whole blood frequencies and enhanced activity in CD8+ T cells, B cells, monocytes, and DCs in Black patients with more active disease. Epigenetic modifications in CD8+ T cells (H3K27ac) could distinguish disease activity level in Black patients and differentiate Black from White patient samples. TLR3/4/7/8/9-related gene expression was elevated in immune cells from Black patients with SLE, and TLR7/8/9 and IFN-α phospho-signaling and cytokine responses were heightened even in immune cells from healthy Black control patients compared with White individuals. TLR stimulation of healthy immune cells recapitulated the ancestry-associated SLE immunophenotypes. This multiomic resource defines ancestry-associated immune phenotypes that differ between Black and White patients with SLE, which may influence the course and severity of SLE and other diseases.