Systemic Lupus Erythematosus Disease Activity Index Research Articles

Expression of hsa-let-7f-5p and serum levels of interleukin-10, cystatin-C and transforming growth factor-beta in systemic lupus erythematosus patients with lupus nephritis

Aim of the workTo investigate the impact of mi-RNA (hsa-let-7f-5p) expression, levels of cystatin C, serum interleukin-10 (IL-10), and transforming-growth-factor-beta (TGF-β) in systemic lupus erythematosus (SLE) patients with and without lupus nephritis (LN). Patients and methodsThe work included 60 SLE patients: thirty with and thirty without LN, along with thirty matched controls. The SLE disease activity index (SLEDAI) was assessed. Enzyme-linked-immunosorbent-assay (ELISA) was used to evaluate serum levels of TGF-β, IL-10, and Cystatin-C and expression of mi-RNA Let-7f-5p quantified using real-time polymerized-chain-reaction (PCR). ResultsThe mean age of LN patients was 31.6 ± 8.4 years, twenty-eight females and 2 males. mi-RNA Let-7f-5p, serum TGFβ, IL10, and cystatin C were significantly higher in those with LN (4.4 ± 2, 357.6 ± 50.8 ng/mL, 173.1 ± 18 pg/mL and 8.03 ± 1.96 ng/mL) compared to case without (2.5 ± 0.92, 319.7 ± 44.4 ng/mL, 108.8 ± 22.8 pg/mL, and 3.43 ± 1.1 ng/mL) and control (1.03 ± 0.07, 210.3 ± 18.6 ng/mL, 56 ± 18.5 pg/mL and 2.53 ± 1.1 ng/ml)(p < 0.001). In LN, mi-RNA Let-7f-5p and IL10 were significantly different in those with oral ulcers (n = 8)(p = 0.03, and p = 0.01 respectively). mi-RNA Let-7f-5p and TGF-β were significantly lower in those with headache (n = 3)(p < 0.001, and p = 0.04 respectively). In patients without LN, TGF-β was significantly lower in those with malar rash (n = 10)(p = 0.04) and serum cystatin-C was lower in those with arthritis (n = 12)(p = 0.02). In LN, IL-10 significantly correlated with disease duration (r = 0.38,p = 0.04) and cystatin-C inversely with platelets (r = -0.42,p = 0.02), Cystatin-C correlated with mi-RNA Let-7f-5p (r = 0.45,p = 0.01) and inversely with SLEDAI (r = -0.44,p = 0.01). ConclusionThe potential role of mi-RNA Let-7f-5p on LN with the possible involvement of TGFβ, IL10, and cystatin-C in the pathophysiology of both SLE and LN.

Efficacy and safety of telitacicept in patients with lupus nephritis: a single-center, real-world retrospective study.

Telitacicept, an innovative drug used for the treatment of systemic lupus erythematosus (SLE), can effectively control disease progression and achieve favorable outcomes. While case reports have mentioned the use of Telitacicept in lupus nephritis (LN) treatment, its safety and efficacy in treating patients with LN have not been explored. Therefore, in this study, we aimed to evaluate the safety and efficacy of Telitacicept in managing patients with LN. In a single-center, real-world retrospective study, 30 LN patients with poor response or adverse reactions to conventional glucocorticoids at our Hospital were enrolled to receive Telitacicept. Patients were administered 160mg of Telitacicept subcutaneously once a week for at least 24weeks in addition to standard treatment. We assessed the SLE responder index-4 (SRI-4) at the beginning and the end of the treatment period, measured laboratory test indicators at 3, 6, and 9months, and observed the occurrence of adverse events in these patients. The SRI-4 response rate was 86.67% (n = 26), with a significantly lower systemic lupus erythematosus disease activity index (SLEDAI) score compared to the baseline. Post Telitacicept treatment, glucocorticoid intake of patients with LN significantly reduced from 50 (IQR:40, 51.25) at baseline to 10 (IQR:5,10) at the endpoint (Z = -6.547, p < 0.001). Patients with LN showed significantly improved urine occult blood levels after Telitacicept therapy. While the complement (C3 and C4) contents increased, immunoglobulins (IgG, IgA and IgM) reduced markedly (p < 0.001). The negative rate of dsDNA reached 26.67% and adverse events were alleviated post treatment. Only two cases of LN-related adverse reactions were reported, including herpes and infectious fever, respectively. Telitacicept primarily serves as an agent for the induction of remission therapy, with an attainment of complete remission rate standing at a commendable 73.3%. Telitacicept treatment reduced disease severity in patients with LN. The initial clinical trial provided supportive evidence for the effectiveness and safety of Telitacicept as a viable treatment option for LN, allowing a reduction in the daily glucocorticoid intake while maintaining a good safety profile, and improving hypocomplementation in LN management.

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.

An observational study to identify causative factors for not using hydroxychloroquine in systemic lupus erythematosus

Hydroxychloroquine (HCQ) use is indicated for patients with systemic lupus erythematosus (SLE). Nevertheless, reports discussing the reasons for not prescribing HCQ are limited. We identified the factors that interfere with HCQ use in patients with SLE. This observational, single-center study included data from 265 patients with SLE in 2019. The patients were categorized into groups with and without a history of HCQ use. Between these groups, clinical characteristics were compared using univariate analysis and logistic regression models. Among the 265 patients, 133 (50.2%) had a history of HCQ use. Univariate analysis identified older age; longer disease duration; lower prednisolone dose, clinical SLE disease activity index 2000, and estimated glomerular filtration rate; higher C3 level; and lower anti-double-stranded DNA antibody concentration as HCQ non-use-related variables. Logistic regression models identified a positive association between HCQ non-use and longer disease duration (odds ratio [OR] 1.08), prednisolone dose ≤ 7.5 mg/day (OR 4.03), C3 level ≥ 73 mg/dL (OR 2.15), and attending physician having graduated > 10 years prior (OR 3.19). In conclusion, a longer disease duration, lower prednisolone dose, higher C3 level, and longer time since attending physicians’ graduation correlated with HCQ non-use. Physicians and patients should be educated to facilitate HCQ use despite these factors.

Management of lupus thrombocytopenia through Ayurveda- A case report

Abstract Immune thrombocytopenic purpura (ITP) is one of the complications of systemic lupus erythematosus (SLE). SLE is often complicated by cytopenias. Thrombocytopenia is usually mild and its frequency ranges from 20% to 40%. There are no evidence-based guidelines that will help choose one drug over another. The present article deals with a case diagnosed with SLE-ITP. In Ayurveda, it can be diagnosed with Raktapitta (lupus thrombocytopenia) and was effectively managed with internal medications based on treatment principles of Jwara (fever) and Raktapitta. The platelet count during the first visit was 0.37/lacs/mm3, which was raised to 190 × 109/L after the management with Ayurvedic principles. SLE disease activity index (SLEDAI) was 13 points on her first visit. After treatment, SLEDAI was reduced to two points. The effectiveness of treatment was assessed by improvement in symptoms and platelet count before and after treatment. There was relief in all the symptoms and increase was also noted in the platelet count after the treatment. Ayurveda can definitely be a treatment modality in treating steroid-dependent SLE-ITP.

Effect of hydroxychloroquine blood concentration on the efficacy and ocular toxicity of systemic lupus erythematosus.

In the absence of evidence-based guidance on the impact of hydroxychloroquine (HCQ) blood concentration on efficacy and ocular toxicity in systemic lupus erythematosus (SLE), the clinical monitoring of HCQ blood concentration is not yet widely performed, which raised concerns about the necessity of conducting HCQ blood concentration monitoring. In this retrospective study, we consecutively enrolled 135 patients with SLE who received HCQ treatment for more than 6months from July 2022 to December 2022. Ocular toxicity was evaluated by collecting relevant retinal parameters using optical coherence tomography angiography (OCTA). Therapeutic efficacy was evaluated using the SLE disease activity index (SLEDAI) and relevant clinical parameters. HCQ blood concentration was determined by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Spearman correlation analysis revealed that the cumulative dose of HCQ was positively correlated with the foveal avascular zone (FAZ) perimeter and FAZ area (r = 0.734, P < 0.001; r = 0.784, P < 0.001). Meanwhile, the treatment duration of HCQ was positively correlated with FAZ perimeter and FAZ area (r = 0.761, P < 0.001; r = 0.882, P < 0.001). The univariate and multivariate logistic regression analyses indicated that HCQ blood concentration was associated with the disease activity of patients with SLE (odds ratio 0.994, 95% CI 0.990-0.999). HCQ blood concentration may be an important factor in assessing the therapeutic effectiveness of SLE patients. The HCQ-related ocular toxicity was a long-term effect related to long term exposure, rather than the blood concentration of HCQ at the time of testing. More importantly, when addressing HCQ-related ocular toxicity, it may be crucial to pay attention to the cumulative dose and treatment duration of HCQ.

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.

The use of belimumab on patients with both systemic lupus erythematosus and immune thrombocytopenia: A retrospective cohort study.

The objective of this study is to provide a description of a group of retrospective cohort outcomes in patients with systemic lupus erythematosus (SLE) complicated with immune thrombocytopenia (ITP) receiving belimumab. This study reports on the treatment of 10 female patients (mean age 34.3 ± 14.0years, mean weight 58.7 ± 18.2kg) with both SLE and ITP who received belimumab in addition to basic drug therapy. The belimumab treatment regimen consisted of a dosage of 10mg/kg, with an initial infusion every 2weeks for the first 3 doses, followed by an infusion every 4weeks. Ten patients were included in the study. The overall response rate of thrombocytopenia was 90% after treatment. The parameters such as platelet count, lymphocyte count, erythrocyte count, hemoglobin, dsDNA, C3, and C4 were significantly improved (p < .05). The SLE Disease Activity Index (SLEDAI), British Islet lupus Assessment Group 2004 (BILAG-2004), and Physician Global assessment (PGA) scores were significantly decreased (p < .05). There were no significant differences in glutamic pyruvic transaminase (ALT), glutamic oxaloacetic transaminase (AST), and serum creatinine (Scr) before and after treatment (p > .05). Belimumab shows promising clinical outcomes in the treatment on patients with both SLE and ITP. Further studies are needed to validate these findings in larger patient populations and compare the efficacy of belimumab with other treatments for SLE complicated with ITP. Long-term response rates and adverse events associated with belimumab treatment also warrant further investigation.

A retrospective cohort study of Epstein-Barr virus infection status and systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) and the Epstein-Barr virus (EBV) are very closely related. This study estimated the impact of EBV infection status on clinical manifestations and disease remission in patients with SLE. A retrospective study was performed using electronic health records of patients with SLE. The SLE disease activity index (SLEDAI-2K) was used to assess disease activity. VCAIgM or EAIgM positive or EBVDNA copies ≥ 50IU/mL were defined as lytic infection group, EBNA-IgG or VCAIgG-positive and who were negative for both VCAIgM and EAIgM with EBVDNA copies < 50IU/mL were defined as the latent infection group. The endpoint (disease remission) was defined as a decrease in SLEDAI-2K score of ≥ 1 grade or ≥ 4 points from baseline. The association between EBV infection status and disease remission was assessed using propensity score weighting and multivariable Cox regression models. There were 75 patients with SLE in the EBV lytic infection group and 142 patients in the latent infection group. The SLEDAI-2K score was higher in the lytic infection group (10.00 (6.25, 16.00) vs. 8.00 (5.00, 10.00), Z = 3.96, P < 0.001). There was a significant difference in the effect of EBV lytic infection on disease remission compared to latent infection (HR 0.30, 95% CI 0.19-0.49, P < 0.001). Patients with SLE with lytic EBV infection have higher disease activity and take longer to achieve remission. Our study furthers our understanding of the relationship between SLE and EBV infection and may inform better treatment practices in the future.

Exploring the interplay of MTHFR and FGG polymorphisms with serum levels of adiponectin and leptin in pediatric lupus nephritis: a pilot study

BackgroundAdiponectin and leptin are pivotal in the regulation of metabolism. Pediatric lupus nephritis (pLN), a manifestation of childhood systemic lupus erythematosus (SLE) affecting the kidneys, is associated with impaired adipokine levels, suggesting a role in pLN pathogenesis. The aim of this study was to explore the potential relationship between specific single-nucleotide polymorphisms (SNPs)—methylenetetrahydrofolate reductase (MTHFR) rs1801131 and fibrinogen gamma chain (FGG) rs2066865—and the serum levels of leptin and adiponectin in patients with pLN.MethodsNinety-eight pLN patients and one hundred controls were enrolled in the study. Serum leptin and adiponectin levels were measured using ELISA. DNA extraction and real-time PCR genotyping were performed for MTHFR rs1801131 and FGG rs2066865 SNPs.ResultsCompared to healthy controls, pLN patients exhibited significantly greater serum leptin (11.3 vs. 18.2 ng/mL, p < 0.001) and adiponectin (18.2 vs. 2.7 ug/mL, p < 0.001). Adiponectin levels were positively correlated with proteinuria (p < 0.05), while leptin levels positively correlated with proteinuria, SLE disease activity index-2000 (SLEDAI-2K), and cyclophosphamide usage (all p < 0.05). There was no significant association between MTHFR rs1801131 or FGG rs2066865 SNPs and pLN in either codominant or allelic models (all p > 0.05). However, the AG genotype of FGG gene rs2066865 SNP was significantly associated with high leptin levels (> 15 ng/mL) (p = 0.01).ConclusionSerum adiponectin and leptin levels are associated with pathological manifestations of pLN. High leptin levels are associated with the AG genotype of FGG rs2066865 SNP in pLN patients, suggesting direct involvement in disease progression and potential utility as a disease biomarker.

Intestinal permeability correlates with disease activity and DNA methylation changes in lupus patients

ObjectiveSystemic lupus erythematosus (SLE or lupus) is a chronic autoimmune disease that can involve various organ systems. Several studies have suggested that increased intestinal permeability may play a role in the pathogenesis of lupus. The aim of this study was to elucidate the relationship between intestinal permeability, disease activity, and epigenetic changes in lupus patients. MethodsA total of 25 female lupus patients were included in this study. Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores were used as indicator of disease activity. Plasma zonulin levels were measured, using an ELISA, as a marker of intestinal permeability. Genome-wide DNA methylation patterns were assessed in neutrophils for 19 of the lupus patients using the Infinium MethylationEPIC array. Linear regression and Pearson's correlation were used to evaluate the correlation between zonulin concentrations and SLEDAI scores. The relationship between DNA methylation levels and zonulin concentrations was assessed using beta regression, linear regression, and Pearson's correlation, adjusting for age and race. ResultsIntestinal permeability positively correlated with disease activity in lupus patients (p-value = 7.60 × 10−3, r = 0.53). DNA methylation levels in 926 CpG sites significantly correlated with intestinal permeability. The highest correlation was identified in LRIG1 (cg14159396, FDR-adjusted p-value = 1.35 × 10−12, adjusted r2 = 0.92), which plays a role in intestinal homeostasis. Gene Ontologies related to cell-cell adhesion were enriched among the genes that were hypomethylated with increased intestinal permeability in lupus. ConclusionOur data suggest a correlation between increased intestinal permeability and disease activity in lupus patients. Further, increased intestinal permeability might be associated with epigenetic changes that could play a role in the pathogenesis of lupus.

Using combination of albumin to fibrinogen ratio and prognostic nutritional index model for predicting disease activity in patients with systemic lupus erythematosus.

Background: Systemic lupus erythematosus (SLE) is chronic autoimmune disease with multiple organ damage and is associated with poor prognosis and high mortality. Identification of universal biomarkers to predict SLE activity is challenging due to the heterogeneity of the disease. This study aimed to identify the indicators that are sensitive and specific to predict activity of SLE.Methods: We retrospectively analyzed 108 patients with SLE. Patients were categorized into SLE with activity and without activity groups on the basis of SLE disease activity index. We analyzed the potential of routine and novel indicators in predicting the SLE activity using receiver operating characteristic curves and multivariate logistic regression. The Spearman method was used to understand the correlation between albumin to fibrinogen ratio (AFR), prognostic nutritional index (PNI), AFR-PNI model and disease activity.Results: SLE with activity group had higher ESR, CRP, D-dimer, fibrinogen, CRP to albumin ratio, positive rate of anti-dsDNA and ANUA, and lower C3, total bilirubin, total protein, albumin, albumin/globulin, creatinine, high density liptein cholesterol, hemoglobin, hematocrit, lymphocyte count, positive rate of anti-SSA, AFR, PNI than SLE without activity. A further established model based on combination of AFR and PNI (AFR-PNI model) showed prominent value in distinguishing SLE with activity patients from SLE without activity patients. In addition, the sensitivity and specificity of AFR-PNI model + anti-dsDNA combination model were superior to AFR-PNI model. AFR and PNI were risk factors for SLE activity. Moreover, AFR+PNI model correlated with disease activity and AFR-PNI model was associated with fever, pleurisy, pericarditis, renal involvement.Conclusion: These findings suggest that predictive model based on combination of AFR and PNI may be useful markers to identify active SLE in clinical practice.

Positive psychological capital, post-traumatic growth, social support, and quality of life in patients with systemic lupus erythematosus: A cross-sectional study.

This study aimed to investigate the correlation between positive psychological capital, post-traumatic growth, social support, and quality of life (QOL) in patients with systemic lupus erythematosus (SLE). A cross-sectional study was conducted at the First Affiliated Hospital of Xinjiang Medical University from October 2022 to May 2023. A sample of 330 hospitalized SLE patients was selected for this study. The collected data included demographic information, the SLE disease activity index, the Positive Mental Capital Questionnaire, the Chinese version of the Post-Traumatic Growth Scale, the Social Support Rating Scale, and the Chinese version of the Lupus Quality of Life Scale. The QOL score among the 330 SLE patients was measured as M(P25, P75) of 105 (83.00,124.00). Positive psychological capital, post-traumatic growth, and social support demonstrated significant positive correlations with the QOL in SLE patients (p < 0.05). Multiple linear regression analysis revealed that literacy, disease level, disease duration, occupation, marital status, psychological capital, social support, and post-traumatic growth were influential factors associated with the QOL in SLE patients. Medical professionals should be attentive to the psychological well-being of SLE patients and should consider implementing early psychological interventions. These interventions are crucial for enhancing the QOL for individuals diagnosed with SLE.

Role of Advanced Glycation End Products as New Biomarkers in Systemic Lupus Erythematosus.

Advanced glycation end-products (AGEs) may play a relevant role as inducers in the chronic inflammatory pathway present in immune-mediated diseases, such as systemic lupus erythematosus (SLE). AGEs concentrations have been associated, with discrepant results to date, with some parameters such as disease activity or accrual damage, suggesting their potential usefulness as biomarkers of the disease. Our objectives are to confirm differences in AGEs levels measured by cutaneous autofluorescence between SLE patients and healthy controls (HC) and to study their correlation with various disease parameters. Cross-sectional study, where AGEs levels were measured by skin autofluorescence, and SLE patients' data were compared with those of sex- and age-matched HC in a 1:3 proportion through a multiple linear regression model. Associations of AGEs levels with demographic and clinical data were analyzed through ANOVA tests. Both analyses were adjusted for confounders. AGEs levels in SLE patients were significantly higher than in HC (p < 0.001). We found statistically significant positive associations with SLE disease activity index (SLEDAI) and damage index (SDI), physician and patient global assessment, C-reactive protein, leukocyturia, complement C4, IL-6 and oral ulcers. We also found a negative statistically significant association with current positivity of anti-nuclear and anti-Ro60 antibodies. AGEs seem to have a contribution in LES pathophysiology, being associated with activity and damage and having a role as a new management and prognosis biomarker in this disease. The association with specific antibodies and disease manifestations may indicate a specific clinical phenotype related to higher or lower AGEs levels.

Correlation of simple hematological parameters with disease activity and damage indices among Egyptian patients with systemic lupus erythematosus

ObjectiveTo evaluate the correlation of different hematological parameters in lupus patients with SLE disease activity index (SLEDAI), the Systemic Lupus International Collaboration Clinics/American College of Rheumatology Damage Index (SLICC/ACR DI), and some laboratory data related to kidney functions in active patients with nephritis. Material and methods80 inactive SLE patients (SLEDAI score<10 points), and 80 active patients (SLEDAI≥10 points) were enrolled in this study. All patients underwent full medical history taking, clinical evaluation including calculation of SLEDAI and SLICC/ACR DI scores, and laboratory investigations including complete blood count. The two groups were compared regarding different disease parameters. Correlations of some hematological parameters with SLEDAI, SLICC/ACR DI scores and some laboratory data related to kidney function in patients with nephritis were made. ResultsThe active group showed statistically significantly higher mean NLR (P=0.000), NC3R (P=0.000), MLR (P=0.000), PLR (P=0.000), and RDW (P=0.001), and statistically significantly lower mean MPV (P=0.002). The mean MLR (P=0.018) and PLR (P=0.005) were statistically significantly higher in the active patients with nephritis. For both groups, there were no significant correlations between studied parameters and SLEDAI or SLICC/ACR DI, except with NC3R values in the active group which were associated with SLEDAI (r=.221, P=0.049). ConclusionThe hematological parameters in SLE have promising potential clinical application as a novel activity marker, especially in patients with nephritis.

Mezagitamab in systemic lupus erythematosus: clinical and mechanistic findings of CD38 inhibition in an autoimmune disease

ObjectiveTo evaluate safety and mechanism of action of mezagitamab (TAK-079), an anti-CD38 monoclonal antibody, in patients with moderate to severe systemic lupus erythematosus (SLE).MethodsA phase 1b double-blind, placebo-controlled, multicentre study...

Evaluation of Type 2 SLE symptoms in patients with a range of lupus nephritis activity.

Type 2 systemic lupus erythematosus (SLE) symptoms, including fatigue, fibromyalgia, and brain fog, contribute to poor health-related quality of life (HRQoL) in patients with lupus. To test the hypothesis that Type 1 (classical inflammatory lupus) activity is associated with Type 2 SLE activity, we characterized the features of Type 2 SLE in patients with a range of lupus nephritis (LN) activity. This was a cross-sectional study of SLE patients [American College of Rheumatology (ACR) 1997 or Systemic Lupus International Collaborating Clinics (SLICC) 2012 classification criteria] from June 2018 to March 2020. Patients completed the Systemic Lupus Activity Questionnaire (SLAQ) and the Polysymptomatic Distress Scale. Patients were divided into groups based on their renal status. Active nephritis was defined using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) lupus nephritis parameter. Differences across groups were analyzed by Fisher's exact test and ANOVA. In this cohort of 244 patients (93% female, mean age 43years, 58% Black), 10% had active nephritis, 35% had historical nephritis, and 55% never had nephritis (non-nephritis). Active nephritis and non-nephritis patients had a similar burden of Type 2 SLE symptoms, despite a difference in Type 1 SLE activity. Patients with active nephritis had higher Type 2 PGA (Physician Global Assessment) scores and reported more Type 2 SLE symptoms than inactive nephritis patients. Patients with inactive nephritis had the lowest Type 2 SLE activity. While Type 2 SLE symptoms are common in SLE, our findings suggest that patients with active nephritis experience significant Type 2 SLE symptoms that may be ameliorated as nephritis improves. We also observed that non-nephritis patients had a similar burden of Type 2 SLE symptoms as patients with active nephritis, despite having on average lower Type 1 SLE activity. Therefore, the etiology of Type 2 SLE symptoms is likely multifactorial and may be driven by inflammatory and non-inflammatory biopsychosocial factors. Key Points • Patients with active nephritis experienced significant Type 2 symptoms that may be ameliorated as nephritis improves. • Non-nephritis patients had a similar burden of Type 2 SLE symptoms as patients with active nephritis, despite having on average lower Type 1 SLE activity. • Because etiology of Type 2 SLE symptoms is likely multifactorial and may be driven by inflammatory and non-inflammatory biopsychosocial factors.

Dysregulated CXCL12 expression in osteoblasts promotes B-lymphocytes preferentially homing to the bone marrow in MRL/lpr mice

Objective: Todetect the abnormal distribution of B-lymphocytes between peripheral and bone marrow (BM) compartments and explore the mechanism of abnormal chemotaxis of B-lymphocytes in lupus subjects. Methods: The proportions of CXC chemokine receptor (CXCR)4+ B cells and CFDA-labeled MRL/lpr-derived B cells were detected by flow cytometry. The levels of CXC chemokine ligand (CXCL)12in peripheral blood (PB)were measured by ELISA. The migrated B cells to osteoblasts (OBs) was measured by transwell migration assay. The relative spatial position of B cells, OBs and CXCL12 was presented by Immunofluorescence assay. Results: Firstly, we found that the percentage of CXCR4+ B cells was lower in PB and higher in the BM from both MRL/lpr mice and patientswith Systemic lupus erythematosus (SLE). Secondly, OBs from MRL/lpr mice produced more CXCL12 than that from C57BL/6 mice. Besides, MRL/lpr-derived OBs demonstrated more potent chemotactic ability toward B-lymphocytes than control OBs by vitro an vivo. Additionally, more B-lymphocytes were found to co-localize with OBs within the periosteal zone of bone in MRL/lpr mice. Lastly, the percentages of CXCR4+B cells were found to be negatively correlated with serum Immunoglobulin (Ig) G concentration, moreover, BM CXCL12 levels were found to be positively correlated with SLE disease activity index Score and negatively correlated with serum Complement3 (C3) concentration. Conclusions: our results indicated that there is a shifted distribution of B-lymphocytes between BM and peripheral compartments in both SLE patients and MRL/lpr mice. Besides, the up-regulated levels of CXCL12 in OBs was indicated to contribute to the enhanced chemotactic migration and anchorage of B-lymphocytes to OBs.

Therapeutic strategies and outcomes in neuropsychiatric systemic lupus erythematosus: an international multicentre retrospective study.

The management of neuropsychiatric systemic lupus erythematosus (NPSLE) poses considerable challenges due to limited clinical trials. Therapeutic decisions are customized based on suspected pathogenic mechanisms and symptoms severity. This study aimed to investigate therapeutic strategies and disease outcome for patients with NPSLE experiencing their first neuropsychiatric (NP) manifestation. This retrospective cohort study defined NP events according to the American College of Rheumatology case definition, categorizing them into three clusters: central/diffuse, central/focal and peripheral. Clinical judgment and a validated attribution algorithm were used for NP event attribution. Data included demographic variables, SLE disease activity index, cumulative organ damage, and NP manifestation treatments. The clinical outcome of all NP events was determined by a physician seven-point Likert scale. Predictors of clinical improvement/resolution were investigated in a multivariable logistic regression analysis. The analysis included 350 events. Immunosuppressants and corticosteroids were more frequently initiated/escalated for SLE-attributed central diffuse or focal NP manifestations. At 12 months of follow-up, 64% of patients showed a clinical improvement in NP manifestations. Focal central events and SLE-attributed manifestations correlated with higher rates of clinical improvement. Patients with NP manifestations attributed to SLE according to clinical judgment and treated with immunosuppressants had a significantly higher probability of achieving clinical response (OR 2.55, 95%CI 1.06-6.41, P = 0.04). Age at diagnosis and focal central events emerged as additional response predictors. NP manifestations attributed to SLE by clinical judgment and treated with immunosuppressants demonstrated improved 12-month outcomes. This underscores the importance of accurate attribution and timely diagnosis of NPSLE.

Histone-Specific CD4+ T Cell Plasticity in Active and Quiescent Systemic Lupus Erythematosus.

The aim of this study was to assess whether circulating histone-specific T cells represent tools for precision medicine in systemic lupus erythematosus (SLE). Seroprevalence of autoantibodies and HLA-DR beta (DRB) 1 profile were assessed among 185 patients with SLE and combined with bioinformatics and literature evidence to identify HLA-peptide autoepitope couples for ex vivo detection of antigen-specific T cells through flow cytometry. T cell differentiation and polarization was investigated in patients with SLE, patients with Takayasu arteritis, and healthy controls carrying HLA-DRB1*03:01 and/or HLA-DRB1*11:01. SLE Disease Activity Index 2000 and Lupus Low Disease Activity State were used to estimate disease activity and remission. Histone-specific CD4+ T cells were selectively detected in patients with SLE. Among patients with a history of anti-DNA antibodies, 77% had detectable histone-specific T cells, whereas 50% had lymphocytes releasing cytokines or upregulating activation markers after in vitro challenge with histone peptide antigens. Histone-specific regulatory and effector T helper (Th) 1-, Th2-, and atypical Th1/Th17 (Th1*)-polarized cells were significantly more abundant in patients with SLE with quiescent disease. In contrast, total Th1-, Th2-, and Th1*-polarized and regulatory T cells were similarly represented between patients and controls or patients with SLE with active versus quiescent disease. Histone-specific effector memory T cells accumulated in the blood of patients with quiescent SLE, whereas total effector memory T cell counts did not change. Immunosuppressants were associated with expanded CD4+ histone-specific naive T (TN) and terminally differentiated T cells. Histone-specific T cells are selectively detected in patients with SLE, and their concentration in the blood varies with disease activity, suggesting that they represent innovative tools for patient stratification and therapy.