Active Systemic Lupus Erythematosus Patients Research Articles

Epstein-Barr Virus Reactivation as a New Predictor of Achieving Remission or Lupus Low Disease Activity State in Patients with Systemic Lupus Erythematosus with Cutaneous Involvement.

Although Epstein-Barr virus (EBV) reactivation has long been associated with the pathogenesis of systemic lupus erythematosus (SLE), many aspects of this relationship remain unclear. Our objective was to investigate the association between EBV reactivation and the achievement of SLE remission and lupus low disease activity state (LLDAS) over a six-month period. Clinical, laboratory, and virological tests (anti-EBV antibodies and EBV DNA) were performed among 51 patients with the active form of SLE on two occasions six months apart. SLE remission and LLDAS achievement were assessed at the end of the follow-up period. Active EBV infection was detected in 45% of active SLE patients at baseline, and 77% transitioned to latent EBV infection at six months (p < 0.001). Multivariate regression revealed a higher titer of anti-EA(D) IgM-Abs and the presence of anti-EA(D) IgM-Abs as independent predictors of remission and LLDAS in SLE patients with mucocutaneous manifestations (p = 0.042) and rash only (p = 0.023), respectively. Since a higher C3 level was an independent predictor of transition to latent EBV infection (p = 0.027), the estimated cut-off value that could identify active SLE patients who will transition to latent EBV infection after six months was ≥0.780 g/L with a sensitivity of 70.6% and a specificity of 75.0% (AUC = 0.756, p = 0.003). EBV reactivation is common in patients with active SLE, and most of them transition to latent EBV infection after six months. Achieving remission and LLDAS in SLE patients with mucocutaneous manifestations can be predicted by a higher titer, whereas in SLE patients who have only a rash, the presence of anti-EA (D) IgM-Abs was a predictor of remission and LLDAS.

Role of Altered Metabolism of Triglyceride-Rich Lipoprotein Particles in the Development of Vascular Dysfunction in Systemic Lupus Erythematosus

Impaired lipid metabolism contributes to accelerated inflammatory responses in addition to promoting the formation of atherosclerosis in systemic lupus erythematosus (SLE). We aimed to evaluate the lipid profile, inflammatory markers, and vascular diagnostic tests in active SLE patients to clarify the association between dyslipidemia and early vascular damage. 51 clinically active SLE patients and 41 age- and gender-matched control subjects were enrolled in the study. Lipoprotein subfractions were detected by Lipoprint. Brachial artery flow-mediated dilation and common carotid intima-media thickness were detected by ultrasonography. Arterial stiffness indicated by augmentation index (Aix) and pulse wave velocity was measured by arteriography. We found significantly higher Aix, higher VLDL ratio, plasma triglyceride, ApoB100, and small HDL, as well as lower HDL-C, large HDL, and ApoA1 in patients with SLE. There was a significant positive correlation of Aix with triglyceride, VLDL, IDL-C, IDL-B, and LDL1. A backward stepwise multiple regression analysis showed IDL-C subfraction to be the best predictor of Aix. Our results indicate that in young patients with SLE, triglyceride-rich lipoproteins influence vascular function detected by Aix. These parameters may be assessed and integrated into the management plan for screening cardiovascular risk in patients with SLE.

Anifrolumab (Saphnelo)

&#x0D; CADTH recommends that Saphnelo be reimbursed by public drug plans in addition to standard therapy for the treatment of adult patients with active, autoantibody positive, systemic lupus erythematosus (SLE).&#x0D; Saphnelo should only be covered to treat adult patients with moderate-severe SLE whose disease cannot be controlled with an oral corticosteroids (OCS) dose of at least 10 mg per day of prednisone or its equivalent in addition to standard of care. Saphnelo should not be covered to treat patients with active severe SLE nephritis or patients with severe or unstable neuropsychiatric SLE.&#x0D; Saphnelo should only be reimbursed if prescribed by a physician with expertise in diagnosing and managing SLE and if the cost of Saphnelo is reduced. Saphnelo should not be covered when used in combination with other biologic treatments. After 12 months of treatment, Saphnelo can be prescribed again for patients who show a reduction in disease activity and reduction in glucocorticoid intake compared to when they first started treatment.&#x0D;

Cell phenotypes as activity biomarkers in patients with Systemic Lupus Erythematosus

The pathogenesis of systemic lupus erythematosus (SLE) is complex. Few studies in Brazilian population have addressed cell phenotypes associated with immunological responses and their associations with SLE activity. The aim of this study is to investigate cell phenotypes associated to SLE diagnosis, treatment and activity. Twenty-eight SLE female patients (17 inactive, 11 active) and 10 healthy women were included in this study. Markers of natural killer (Nk), T and B cells in peripheral blood were evaluated by flow cytometry. Nkt cells were decreased only in SLE active patients. Activated CD4+, regulatory T FoxP3+ and B cells were decreased in both active and inactive SLE patients, compared to control group. The data corroborate the disruption of immune regulatory response in SLE patients and suggest phenotipic changes as possible biomarkers of SLE activity.

Mesenchymal Stem Cells Suppress Dendritic Cells and Modulate Proinflammatory Milieu Through Interleukin-10 Expression in Peripheral Blood Mononuclear Cells of Human Systemic Lupus Erythematosus.

Immune-mediated inflammatory injury among systemic lupus erythematosus (SLE) individuals may be involved by dendritic cells (DCs) abnormality though the underlying mechanism remains incompletely understood. This study aimed to elaborate MSCs' potential in suppressing abnormal DCs cell function on peripheral blood mononuclear cells (PBMCs) among SLE patients. MSCs were isolated from human umbilical cord blood. On the other side, human PBMCs were isolated from 20 active SLE patients and 5 healthy controls. The PBMCs of SLE patients were divided into 5 groups: sham (Sh) and control (C) groups were treated with standard medium, and the treatment groups (T1, T2 and T3) was co-cultured with hUC-MSC at doses of 1:1, 1:25, and 1:50 (MSCs:PBMCs). The expression of CD11c in DCs was analyzed using flow cytometry, while the level of TNF-α, IFN-γ, IL-6 and IL-10 was analyzed using cytometric bead array (CBA). The MSCs significantly downregulates CD11c of dendritic cells in all treatment groups. MSCs also significantly suppress the level of TNF-α, IFN-γ, IL-6 and the significantly enhance IL-10 level in all treatment groups. Therefore, MSCs could suppress DCs through regulating the proinflammatory milieu in PBMCs of SLE patients.

Urine Galectin-3 binding protein reflects nephritis activity in systemic lupus erythematosus.

Lupus nephritis (LN) is a major and severe organ involvement in systemic lupus erythematosus (SLE), whose diagnosis and treatment necessitate to perform kidney biopsy, which is an invasive procedure. Non-invasive urine biomarkers are an active area of investigation to support LN diagnosis and management. To investigate the role of urinary galectin-3 binding protein (u-Gal-3BP) as a candidate biomarker of renal disease in biopsy proven LN. Levels of u-Gal-3BP were investigated in a cross-sectional fashion by ELISA in 270 subjects: 86 LN patients, 63 active SLE patients with no kidney involvement, 73 SLE patients with inactive disease and 48 age and sex-matched population-based controls (PBC). Moreover, urine samples were analysed separately by ELISA for additional markers of kidney pathology: neutrophil gelatinase-associated lipocalin (NGAL), osteopontin (OPN), kidney injury molecule-1 (KIM-1) and galectin-3 (Gal-3). The concentrations of all studied molecules were normalized to urine creatinine levels. In 10 patients, post-treatment levels of the biomarkers were measured. Normalized u-Gal-3BP levels were higher in LN patients compared to the other groups (p < .0001). Comparing different LN classes, u-Gal-3BP levels were higher among patients with proliferative (class III/IV) and membranous (class V) as compared to mesangial (class II) forms (p = .04). In proliferative forms, u-Gal-3BP levels correlated with the activity index in renal biopsies (r = 0.42, p = .004). Moreover, in a subset of 10 patients with repeated kidney biopsy and urine sampling before and after induction treatment, a significant decrease of u-Gal-3BP was observed (p = .03). Among the other markers, KIM-1 was also able to discriminate LN from the other groups, while NGAL, OPN and Gal-3 could not in this cohort. Given its ability to discriminate LN patients from active non-renal and inactive SLE patients, the observed correlation with the activity index in renal biopsies, and its levels declining following treatment, u-Gal-3BP shows promise as a non-invasive urinary biomarker to help detecting and to monitor renal involvement in SLE patients and should be validated in larger cohorts.

Vitamin D Receptor (VDR) Genetic Variants: Relationship of FokI Genotypes with VDR Expression and Clinical Disease Activity in Systemic Lupus Erythematosus Patients.

Vitamin D (VD) deficiency is more frequent in systemic lupus erythematosus (SLE) patients than in control subjects (CS); genetic variants in the VD receptor (VDR) could contribute to the clinical disease activity. This study was aimed to determine the association of the VDR variants FokI (rs2228570), BsmI (rs1544410), ApaI (rs7975232), and TaqI (rs731236) with susceptibility to the disease, VD status, VDR mRNA expression, and clinical disease activity in SLE patients. A cross-sectional study was conducted in 194 SLE and 196 CS Mexican women. Immunoassays quantified serum calcidiol and calcitriol. Genotyping was performed by allelic discrimination assays and mRNA VDR expression by qPCR. The FokI variant was not in linkage disequilibrium with BsmI, ApaI, and TaqI&nbsp;VDR variants. SLE patient carriers of the TT FokI genotype showed higher clinical disease activity scores. Notably, the mRNA VDR expression was higher in SLE patients vs. CS, in active vs. inactive SLE patients, and in participants of both study groups with vitamin D deficiency, higher calcitriol levels, and TT FokI genotype carriers. In conclusion, the TT FokI VDR genotype was related to high VDR expression and clinical disease activity in systemic lupus erythematosus patients.

Abnormal lower expression of GPR183 in peripheral blood T and B cell subsets of systemic lupus erythematosus patients

G protein-coupled receptor 183 (GPR183) has been indicated to mediate the migration and localisation of immune cells in T cell-dependent antibody responses. Systemic lupus erythematosus (SLE) is a canonical autoimmune disease involving B cell-mediated tolerance destruction and excessive pathogenic autoantibody production, in which multiple GPCRs play a role. To date, there has been no systematic study regarding the expression of GPR183 in lymphocyte subsets of SLE patients. In this research, firstly, we observed the expression trends of GRP183 in various T and B cell subsets in human tonsil tissues. These lymphocyte subsets include CD4+, CD8+, naïve T, effector T, Tfh, activated Tfh, Th1, Th2, Th17, Treg, CD19+CD27-, CD19+CD27+, naïve B, germinal centre B, memory B, and plasma cells. Further, compared with healthy controls (HCs), GPR183 expression levels in above peripheral blood lymphocyte subsets of patients with SLE were reduced overall. The differential expression of GPR183 expression between inactive and active SLE patients indicates that GPR183 expression may be concerned with the disease activity of SLE. This was further confirmed through the strong negative correlation with SLEDAI score and positive correlation with serum complement protein C3, C4 and C1q levels. Further receiver operating characteristic (ROC) curve analysis revealed that GPR183 expression in circulating CD27-IgD+ B cells may be beneficial in distinguishing between inactive and active SLE patients. In addition, type I interferon stimulation could down-regulate the expression of GPR183 in peripheral blood T and B cell subsets. Aberrant expression of GPR183 may provide some novel insights into disease activity prediction and underlying pathogenesis of SLE.

Lack of Association Between Sex Hormones, MDSCs, LDGs and pDCs in Males and Females With Systemic Lupus Erythematosus.

Plasmacytoid dendritic cells (pDCs) and low-density granulocytes (LDGs) are interferon-alpha producing cells that create a pro-inflammatory response in Systemic Lupus Erythematosus (SLE) leading to auto antibody production and organ damage. Both pDCs and LDGs have been shown to be dysfunctional in patients with active SLE. Myeloid-derived suppressor cells (MDSCs) have the capacity to control T and B cell activation and differentiation, and have recently been identified as cells of interest in SLE as well. While not fully understood, previous studies have suggested that pDCs are regulated in part by both X chromosome inactivation and estradiol. Whether sex chromosomes or sex hormones regulate MDSCs and LDGs remain to be determined. We aimed to explore the relative role of sex and sex hormones on pDC, MDSC and LDG frequency and function in SLE patients. We recruited patients with SLE as defined by ACR or SLICC classification criteria and healthy controls in conjunction with the Cleveland Clinic Lupus Cohort and Clinical Research Unit. We analyzed serum sex hormone levels by ELISA, and frequencies of pDCs, MDSCs, and LDGs among PBMCs and serum cytokine levels by flow cytometry. PBMCs were further analyzed for expression of genes involved in or induced by toll-like receptor (TLR)7 or TLR9 stimulation. In all SLE patients, the serum estradiol/testosterone ratio and levels of granulocytic MDSCs and LDGs were increased, while levels of pDCs were decreased. Furthermore, pDCs from active SLE patients expressed lower levels of TLR7 and TLR9 and showed diminished production of TLR9-induced IFNα and TNFα as compared to healthy controls. LDGs from healthy controls and SLE patients expressed very low levels of TLR7 and TLR9 and largely failed to respond to TLR9 stimulation. Thus, regardless of sex and sex-hormone levels, frequencies of pDCs, MDSCs and LDGs, TLR7 and TLR9 expression, and TLR9-driven cytokine production were similarly altered in male and female SLE patients.

The Effect of TLR9, MyD88, and NF-κB p65 in Systemic Lupus Erythematosus.

Purpose This study was conducted to characterize the expression level of peripheral blood toll-like receptors 9 (TLR9), nuclear factor kappa-B protein 65 (NF-κB p65), and myeloid differentiation factor88 (MyD88) of active systemic lupus erythematosus (SLE) and analyse their clinical significance. Methods The prospective cohort study enrolled 30 active SLE patients (SG1 group), 30 stable SLE patients (SG2 group), and 20 healthy individuals (RG group) in the First Affiliated Hospital of Hainan Medical University between January 2018 and June 2020. All SLE patients were treated with methylprednisolone tablets. Quantitative polymerase chain reaction (qPCR) was used to determine the levels of TLR9, MyD88, and NF-κB p65 in the peripheral blood mononuclear cell (PBMC). ELISA was adopted for the determination of serum interleukin (IL-6) and tumor necrosis factor-α (TNF-α). Results Patients in SG1 showed the highest mRNA levels of TLR9, MyD88, and NF-κB p65, followed by SG2, and then RG. SG1 had the highest serum levels of IL-6 and TNF-α, followed by SG2 and RG. The level of TLR9 was positively correlated with the SLE disease activity index (SLEDAI) and negatively correlated with complement component 3 (C3) and complement component 4 (C4). MyD88 and NF-κB p65 were positively correlated with SLEDAI. Conclusion Compared with a healthy status, SLE induces an increase in TLR9, MyD88, NF-κB p65, IL-6, and TNF-α levels, and the activation of the TLR9-MyD88-NF-κB p65 signal path was associated with the pathogenesis of SLE.

Safety and efficacy of fecal microbiota transplantation for treatment of systemic lupus erythematosus: An EXPLORER trial

Gut microbiota dysbiosis is involved in the development of systemic lupus erythematosus (SLE). The safety and efficacy of fecal microbiota transplantation (FMT) for the treatment of SLE patients has not been explored. In this 12-week, single-arm pilot clinical trial of oral encapsulated fecal microbiome from healthy donors to patients with active SLE, we aimed to evaluate the safety and efficacy of FMT in patients with SLE (ChiCTR2000036352). 20 SLE patients with SLEDAI ≥6 were recruited. FMT was administered once a week for three consecutive weeks along with standard treatment and the patients were followed for 12 weeks. Safety was evaluated throughout the trial. The primary endpoint was the SLE Responder Index-4 (SRI-4) at week 12. Microbiome composition, levels of short chain fatty acids (SCFAs) in the gut and of cytokines in the sera were measured along with lymphocyte phenotyping. No serious adverse events were observed after FMT. At week 12, the SRI-4 response rate was 42.12%, and significant reductions in the SLEDAI-2K scores and the level of serum anti-dsDNA antibody were observed compared to baseline. Significant enrichment of SCFAs-producing bacterial taxa and reduction of inflammation-related bacterial taxa were observed, along with increased production of SCFAs in the gut and reduced levels of IL-6 and CD4+ memory/naïve ratio in the peripheral blood. Furthermore, SRI-4 responding patients displayed specific microbiota signatures both before and after FMT. The first clinical trial of FMT in active SLE patients provide supportive evidence that FMT might be a feasible, safe, and potentially effective therapy in SLE patients by modifying the gut microbiome and its metabolic profile.

P242 Immunosuppressants can modify the transcriptomic signature in patients with systemic lupus erythematosus

Abstract Background/Aims Transcriptomics has the potential to revolutionise the way we approach complex diseases such as systemic lupus erythematosus (SLE), which is both clinically and biologically heterogeneous. We aimed to explore whether deconvolution of whole blood transcriptomic data could predict differences in immune cell proportions between active SLE patients, and whether these are attributable to the SLE phenotype or medication use. Methods Patients with active SLE were recruited from the BILAG-Biologics Registry (BILAG-BR) prior to change in therapy. Disease activity was measured using the BILAG-2004 Index. Whole blood RNA-sequencing was conducted at baseline and FPKM-normalised data was deconvoluted using CIBERSORTx with the LM22 signature matrix used as reference. The effects of five different drugs (azathioprine, cyclophosphamide, hydroxychloroquine, methotrexate and mycophenolate mofetil [MMF]) were explored. Predicted cell frequencies were compared between active disease domains (defined by BILAG A or B score) and concomitant immunosuppressant use using Mann-Whitney U tests with Benjamini-Hochberg correction (significance at p &amp;lt; 0.05). Results We recruited 109 patients of whom 104 (95.4%) were female, with a median (IQR) age of 38 years (29-49) years, disease duration of 10 (6.5, 16.5) years. Patients had active disease with a median SLEDAI score of 8 (4-14). For patients taking MMF (53/109, 46.8%), there was a lower proportion of macrophages M0 (0.435% vs 1.391%, p = 0.001), naïve CD4 T cells (0.961% vs 2.251%, p = 0.002) and regulatory T cells (1.858% vs 3.574%, p = 0.007), and a higher proportion of memory activated CD4 T cells (1.826% vs 1.113%, p = 0.015), when compared to patients not taking mycophenolate mofetil. MMF use was associated with statistically significant differences in predicted immune cell (macrophages m0, naïve CD4 T cells, regulatory T cells and memory activated CD4 T cells) frequency after adjusting for age, gender, ethnicity, disease duration, renal disease and steroid use. No differences were observed for the other immunosuppressants or between patients with active or inactive disease in each of the nine organ domains. Conclusion The use of immunosuppressants can significantly modify the transcriptomic signature in patients with SLE affecting key immune cell type populations differently, highlighting the need to adjust for background medication use in future studies, particularly in those using whole blood transcriptomics. It would also be valuable to evaluate the differences identified in this study to determine whether they can be used to monitor or predict treatment response. Disclosure M. Akthar: None. N. Nair: None. O. MASTERPLANS Consortium and BILAG BR Investigators: None. I.N. Bruce: None. J.A. Reynolds: None.

Subclinical left ventricular dysfunction during systemic lupus erythematosus activity with follow-up after remission – A speckle tracking echocardiographic study

Aim of the workTo investigate the subclinical left ventricular (LV) dysfunction in patients with active systemic lupus erythematosus (SLE) using speckle tracking echocardiography (STE). The echocardiographic parameters were followed up when the disease activity was controlled. Patients and methodsThis prospective study included 63 patients with active SLE and LV ejection fraction (EF) ≥50%.Safety of Estrogens in Lupus Erythematosus: National Assessment – Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) was assessed and categorized as mild/moderate (≤12) or severe (>12). Fifty SLE patients continued follow-up after 3–6 months of the disease remission. Fifty age- and gender-matched healthy individuals acted as the control group. The measured STE parameters included LV deformation (global longitudinal strain [GLS] and global circumferential strain [GCS]) and rotational parameters (rotation, twist, and torsion). ResultsThe patients were 56 females and 7 males (F:M 8:1) and median age 26 years (IQR: 21–31 years) and a disease duration of 3 years (IQR 2–5 years. Active SLE patients showed worse strain parameters than controls (mean GLS −19.9%±2.1 vs −22.7%±1.3 and mean GCS −21.2 ± 2.5% vs −25.1 ± 1.7% respectively; p < 0.001 for both). Patients had lower LV rotational parameters (p < 0.001 for all). STE parameters were similar in patients with mild-moderate and severe activity and improved after remission in both groups. ConclusionActive SLE patients had modest LV dysfunction by STE despite having normal function by traditional echocardiography. Disease remission resulted in the improvement of STE parameters. STE is a simple tool to use in SLE activity scores to detect early cardiac dysfunction.

Serum amyloid A-to-albumin ratio as a potential biomarker to predict the activity, severity, and poor prognosis of systemic lupus erythematosus.

ObjectivesTo evaluate the predictive value of serum amyloid A‐to‐albumin ratio (SAR) for active systemic lupus erythematosus (SLE), severe active SLE, and poor prognosis of SLE.MethodsOne hundred and eighty‐six patients with SLE undergoing treatment in our hospital were selected. The demographic characteristics, clinical data, and disease prognosis of all patients were collected and analyzed.ResultsThere were significant differences in SLEDAI, total glyceride (TG), serum amyloid A (SAA), SAR, urinary microalbumin‐to‐creatinine ratio (ACR), erythrocyte sedimentation rate (ESR), albumin (ALB), complement 3 (C3), anti‐dsDNA, anti‐Sm positive rate, and anti‐dsDNA positive rate between active SLE and stable SLE patients. TG, SAR, C3, ACR, and positive anti‐dsDNA were independent influencing factors of active SLE, and the odds ratio (OR) values were 2.342, 10.921, 0.832, 1.451, and 2.476, respectively. The area under curves (AUCs) of SAA, ALB, and SAR for predicting active SLE and severe active SLE were 0.743, 0.724, 0.787, 0.711, 0.686, and 0.733, respectively. The AUC of SAR for predicting the poor prognosis of active SLE was 0.719. High SAR, high ACR, low C3, and positive anti‐dsDNA were high risk factors for poor prognosis. Kaplan–Meier (K‐M) survival analysis showed that patients with high SAR, high ACR, low C3, and positive anti‐dsDNA had shorter continuous remission time than that with low SAR, low ACR, high C3, and negative anti‐dsDNA.ConclusionSAR had high predictive value for active SLE, severe active SLE, and poor prognosis of SLE. High SAR may be a potential marker for predicting the activity and prognosis of Chinese patients with SLE.

Elevated serum free IL-18 in neuropsychiatric systemic lupus erythematosus patients with seizure disorders

Since dysregulation of total Interleukin (IL)-18 and IL-18 binding protein (IL-18BP) may participate in systemic lupus erythematosus (SLE) and contribute to the occurrence of non-autoimmune epilepsy, the aim of the current work is to investigate whether the interaction between IL-18 and IL-18BP plays any role in neuropsychiatric systemic lupus erythematosus related seizures. Data from 137 SLE patients and 30 healthy controls (HC) were consecutively collected from 2020 to 2021. Serum levels of total IL-18 and IL-18BP for all patients and HC were measured by ELISA test. Free IL-18 was calculated based on the law of mass action. Among the 137 SLE patients, 103 had active disease and were classified into NPSLE (n = 50) and Non-NPSLE (n = 53) groups. Among the NPSLE patients, 16 had seizure disorders. Serum free IL-18 levels were increased in NPSLE (277.6 [150.9-428.8]pg/mL) and were correlated with disease activity (r = 0.268, p = 0.002). Moreover, serum free IL-18 levels in NPSLE patients with seizure disorders (350.9 [237.9-455.9]pg/mL) were significantly higher than the levels in those with other neuropsychiatric symptoms (237.7 [124.6-428.8] pg/mL). The expression of free IL-18 was increased in neuropsychiatric systemic lupus erythematosus(NPSLE), especially in NPSLE related seizures. Also, serum levels of free IL-18 were significantly increased in active SLE patients. In this regard, free IL-18 may be involved in the pathogenesis of NPSLE related seizures and associated with disease activity.

Proportion of B cell subsets and Nrf2 mediated redox regulation in systemic lupus erythematosus patients

Systemic lupus erythematosus (SLE) is characterized by expansion of autoreactive lymphocytes and impaired management of oxidative stress. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) plays a significant role in maintaining the redox homeostasis of cell. The present study aims to investigate the frequency of peripheral B cell subsets and the redox regulation by Nrf2 in SLE patients with variable disease activity. For this, a total of forty (40) SLE patients and twenty (20) age and gender-matched healthy controls (HCs) were recruited where patients with SLEDAI < 6 were grouped as Inactive SLE (n = 20) and patients with SLEDAI ≥ 6 were grouped as Active SLE (n = 20). A proportion of peripheral B cell subsets, level of ROS and expression of Nrf2 and Keap1 were studied with the help of flow cytometry and multiplex cytokine bead assay was exploited to estimate the serological concentration of cytokines. The frequency of B cell subsets was significantly altered and correlated with SLEDAI score. Concentration of IFNα2, IFN-β, BAFF, APRIL and IL-6 was also raised in active SLE patients. Moreover, the level of cytosolic ROS was universally decreased while mitochondrial ROS was increased in B cell subsets. The expression of Nrf2 and Keap1 (a negative regulator of Nrf2) was significantly increased in B cell subsets of SLE patients. Here, it has been demonstrated that the frequency of peripheral B cell subsets varies with modification in the SLE disease activity. The given data also demonstrated that the expression of Nrf2 is significantly heightened in B cell subsets to deal with free radical stress.

Amount of dissipative energy loss when assessing left ventricular dysfunction in female patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is associated with an increased risk of cardiovascular disease. The purpose of the current study was to explore the amount of energy loss (EL) using vector flow mapping (VFM) in the detection of early stage left ventricular (LV) dysfunction among patients with SLE. Eighty-nine patients with SLE and fifty-six healthy controls were enrolled. SLE patients were further divided into inactive (SLEDAI ≤ 4, n = 43) and active (SLEDAI ≥ 5, n = 46) subgroups. A prosound F75 echocardiography machine was used for echocardiographic examination. Intra-cardiac flow images were analysed by a VFM workstation. Compared with the healthy group, the inactive SLE group had increased diastolic EL values (38.05 mW/m vs. 33.02 mW/m, p = 0.010). However, the systolic EL values were comparable between the inactive SLE group and the control group (26.07mW/m vs 23.15 mW/m, p = 0.105). The active SLE group exhibited significantly higher diastolic (104.13mW/m vs 33.02mW/m, p < 0.001) and systolic (48.83 mW/m vs 23.15mW/m, p < 0.001) EL values than the control group. The most notable correlation was observed between the values of the diastolic EL and SLEDAI in the inactive SLE group (r = 0.633, p < 0.001) and in the active SLE group (r = 0.824, p < 0.001). LV-dissipative EL assessed by using VFM is useful and feasible for estimating lesions of LV systolic and diastolic function in active SLE patients with preserved left ventricular ejection fraction. Increased disease activity may lead to increased risk of LV dysfunction.

Salivary anti-nuclear antibody (ANA) mirrors serum ANA in systemic lupus erythematosus

ObjectivesTo assay salivary anti-nuclear antibody (ANA) and its isotypes in patients with systemic lupus erythematosus (SLE) and to investigate relevant clinical associations.MethodsSaliva samples were collected from SLE patients and assayed for salivary ANA using immunofluorescence (IF). Isotypes of salivary ANA, including IgG-ANA, IgA-ANA, and IgM-ANA, were quantified using enzyme-linked immunosorbent assay. The correlations between clinical parameters and levels of salivary ANA and isotypes were evaluated.ResultsSalivary ANA IF intensities were significantly higher in SLE patients than in healthy controls, irrespective of SLE patient disease activity, and strongly correlated with serum ANA titers. Salivary ANA was detected in 67.14% of SLE patients and 10.00% of healthy controls (p < 0.001). Among ANA-positive samples, 80.85% exhibited a nuclear ANA pattern, and 42.55% exhibited a cytoplasmic ANA pattern. Salivary IgG-ANA, IgA-ANA, and IgM-ANA levels, as assayed by ELISA, were significantly increased in both active and less active SLE patients compared with healthy controls, and levels of each isotype were significantly correlated with serum ANA titer. Salivary IgM-ANA levels correlated with the physician global assessment (PGA), SLE disease activity index (SLEDAI), and negatively with serum C3 and C4. Salivary IgG-ANA also correlated with erythrocyte sedimentation rate (ESR), SLEDAI, and negatively with serum C3.ConclusionSalivary ANA levels correlate with serum ANA titer, and salivary IgM-ANA and IgG-ANA correlate variably with PGA, SLEDAI, ESR and complement levels. These findings underscore the potential of using salivary ANA and ANA isotypes as surrogates for serum ANA, particularly for future point-of-care applications since saliva is easier to obtain than blood.

Association of High Calcitriol Serum Levels and Its Hydroxylation Efficiency Ratio with Disease Risk in SLE Patients with Vitamin D Deficiency.

Vitamin D (calcidiol) deficiency in systemic lupus erythematosus (SLE) is more frequent than in healthy subjects (HS); it is associated with clinical activity and damage in SLE. Although calcidiol is considered the best indicator of the vitamin D serum status, its deficiency could not reflect its hydroxylation efficiency ratio and calcitriol serum status. This study was aimed at assessing the association of calcidiol and calcitriol serum levels and its hydroxylation efficiency ratio with the risk to clinical and renal disease activities in SLE patients. A cross-sectional study was conducted in 308 SLE and HS women; calcidiol and calcitriol serum levels were evaluated by immunoassays. SLE patients showed lower calcidiol serum levels vs. HS (21.2 vs. 24.2 ng/mL; p < 0.001). Active SLE patients presented higher calcidiol/calcitriol ratio scores vs. inactive SLE patients (2.78 vs. 1.92 pg/ng; p = 0.02), and SLE patients with renal disease activity showed a pattern of calcidiol-deficient levels (19.5 vs. 25.3 ng/mL; p < 0.04) with higher calcitriol levels (47 pg/mL vs. 41.5 pg/mL; p = 0.02) and calcidiol/calcitriol ratio scores (2.13 vs. 1.54 pg/ng; p < 0.02) compared to SLE patients without renal disease activity. Calcidiol levels were negatively correlated with calcitriol levels (r = −0.26; p = 0.001) and urine proteins (mg/dL) (r = −0.39; p < 0.01). Regarding calcitriol levels, it was positively correlated with the blood lymphocyte count (r = 0.30; p < 0.001) and negatively correlated with the glomerular filtration rate (r = −0.28; p = 0.001). Moreover, the calcitriol/calcidiol ratio was positively correlated with urine proteins (r = 0.38; p < 0.01). The calcidiol deficiency (OR = 2.27; 95% CI = 1.15-4.49; p < 0.01), high calcitriol levels (T3rd, OR = 4.19, 95% CI = 2.23-7.90; p < 0.001), and a high calcitriol/calcidiol ratio score (T3rd, OR = 5.93, 95% CI: 3.08-11.5; p < 0.001) were associated with the risk for SLE. In conclusion, a pattern of calcidiol deficiency with high calcitriol serum levels and a high vitamin D hydroxylation efficiency ratio was associated with disease risk in SLE patients.

Lupus gut microbiota transplants cause autoimmunity and inflammation

BackgroundThe etiology of systemic lupus erythematosus (SLE) is multifactorial. Recently, growing evidence suggests that the microbiota plays a role in SLE, yet whether gut microbiota participates in the development of SLE remains largely unknown. To investigate this issue, we carried out 16 s rDNA sequencing analyses in a cohort of 18 female un-treated active SLE patients and 7 female healthy controls, and performed fecal microbiota transplantation from patients and healthy controls to germ-free (GF) mice. ResultsCompared to the healthy controls, we found no significant different microbial diversity but some significantly different species in SLE patients including Turicibacter genus and other 5 species. Fecal transfer from SLE patients to GF mice caused GF mice to develop a series of lupus-like phenotypic features, including increased serum autoimmune antibodies, imbalanced cytokines, altered distribution of immune cells in mucosal and peripheral immune response, and upregulated expression of genes related to SLE in recipient mice that received SLE fecal microbiota transplantation (FMT). Moreover, the metabolism of histidine was significantly altered in GF mice treated with SLE patient feces, as compared to those which received healthy fecal transplants. ConclusionsOverall, our results describe a causal role of aberrant gut microbiota in contributing to the pathogenesis of SLE. The interplay of gut microbial and histidine metabolism may be one of the mechanisms intertwined with autoimmune activation in SLE.