Systemic Lupus Erythematosus Disease Activity Research Articles

Detection of genetic mutations underlying early-onset systemic lupus erythematosus.

We aimed to investigate the presence of monogenic causes of systemic lupus erythematosus (SLE) in our early-onset SLE patients. Fifteen pediatric SLE cases who had early disease onset (≤6 years) were enrolled in this study. All patients fulfilled the Systemic Lupus International Collaborating Clinics (SLICC) criteria. Genomic DNA was used for whole exome sequencing (WES). Pathogenic variants were confirmed by Sanger sequencing. The median age at diagnosis of 15 early-onset SLE patients included in the study was 4 (2-6) years (F/M = 12/3). Significant gene mutations were detected in five of these patients (33.3%). Patients 1 and 2 with homozygous DNASE1L3 mutations [c.320+4_320+7del and G188A (c.563G>C) variants] had skin involvement and oral ulcers. One of them (patient 1) had arthritis and nephritis, and another (patient 2) had nonscarring alopecia and thrombocytopenia. They are currently clinically inactive but have positive serological findings. Patient 3 with homozygous pathogenic ACP5 mutation [G109R (c.325G>A) variant] had arthritis, nephritis, short stature, and skeletal dysplasia. Patient 4 with a heterozygote novel IFIH1 mutation [L809F (c.2425C>T) variant] had skin findings and leukopenia. Patient 5 with novel C1S variant [homozygous C147W (c.441C>G) variant] had marked skin findings, oral ulcers, nonscarring alopecia, pancytopenia, and low total hemolytic complement CH50 level. All patients have responded to the treatments and have low Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores, on therapy. Genetic causes should be investigated in early-onset SLE, for better management and genetic counseling. On the other hand, multicenter studies may help to further define genotype-phenotype associations.

Neutrophils-derived Parameters as Cost-effective Inflammatory, Disease Activity Marker in Systemic Lupus Erythematosus (SLE) and Role in Prediction of Lupus Nephritis

Introduction: Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease with various clinical manifestations and approximately 50% of the SLE patients develop lupus nephritis (LN), which increases the risk of renal failure, cardiovascular diseases and overall survival. Objectives: Evaluation of neutrophil-derived parameters (Neut-X, Neut-Y and Neut-Z) as an inflammatory, disease activity marker and as a predictor of nephritis in SLE patients. Material and Methods: In this cross-sectional study, 3 ml K3EDTA blood was taken from 110 SLE patients presented in Department of Clinical Immunology to evaluate neutrophil-derived parameters in Sysmex XT2000i haematology analyser and their correlation with other inflammatory biomarkers like, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) as well as SLE disease activity index-2000 (SLEDAI-2K). 24-hours urine protein levels were also estimated as a marker of renal involvement. Records of renal biopsy were available in 73 SLE patients, who belonged to different morphologic classification of LN. Results: After performing bivariate Spearman correlation analysis (SPSS software, version 26.0), Neut-X (measures cytoplasmic granularity by side scattering) and Neut-Z (vector sum of Neut-X and Neut-Y) showed a significant positive correlation ( r > 0.200, P < .05) with ESR, CRP and SLEDAI-2K while Neut-Y (measures nucleic acid content by sideward fluorescence) showed a significant negative correlation ( r > 0.200, P < .05) with ESR and CRP. Receiver-operating characteristic curve analysis was used to evaluate diagnostic value of 24-hour urine protein and predictive values of neutrophil-derived parameters for renal involvement in SLE patients. Among neutrophil-derived parameters, Neut-X was found to be the best predictor of renal dysfunction with highest AUC of 0.710 (95% CI: 0.604-0.816; cut-off: 1344.50; sensitivity: 84.7%; specificity: 50%) followed by Neut-Z with AUC of 0.707 (95% CI: 0.600-0.813; cut-off: 1403.67; sensitivity: 87.5%; specificity: 50%). Conclusion: Our study shows that neutrophil-derived parameters may be used as novel cost-effective, non-invasive biomarker of disease activity as well as for predicting renal involvement in SLE patients.

Resolvin D1 inhibits T follicular helper cell expansion in systemic lupus erythematosus

Objective Resolvin D1 (RvD1) is one of the specialized pro-resolving lipid mediators, which control inflammation resolution and regulate immune responses. Previous research showed that RvD1 could block the progression of systemic lupus erythematosus (SLE). However, the detailed mechanism remains to be fully understood. Method Plasma RvD1 levels, and proportions of T follicular helper cells (Tfh cells) were measured in SLE patients and healthy controls. Plasma RvD1 levels and proportions of Tfh cells were quantitated in an MRL/lpr mouse model of lupus treated with RvD1. Naïve CD4+ T cells were purified from MRL/lpr mice to study the effect of RvD1 on Tfh cell differentiation in vitro. Results In patients, there were significant negative correlations between plasma RvD1 levels and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, as well as between plasma RvD1 and anti-double-stranded DNA antibody levels, and numbers of peripheral Tfh cells and plasma cells. In MRL/lpr mice, the expected amelioration of disease phenotype and inflammatory response with RvD1 treatment correlated with decreased percentages of Tfh cells and plasma cells. In addition, the differentiation and proliferation of Tfh cells were markedly suppressed by RvD1 in vitro. Conclusion RvD1 may control SLE progression through the suppression of Tfh cell differentiation and subsequent inhibition of B-cell responses.

Identification of immune subsets with distinct lectin binding signatures using multi-parameter flow cytometry: correlations with disease activity in systemic lupus erythematosus

ObjectivesCell surface glycosylation can influence protein-protein interactions with particular relevance to changes in core fucosylation and terminal sialylation. Glycans are ligands for immune regulatory lectin families like galectins (Gals) or sialic acid immunoglobulin-like lectins (Siglecs). This study delves into the glycan alterations within immune subsets of systemic lupus erythematosus (SLE).MethodsEvaluation of binding affinities of Galectin-1, Galectin-3, Siglec-1, Aleuria aurantia lectin (AAL, recognizing core fucosylation), and Sambucus nigra agglutinin (SNA, specific for α-2,6-sialylation) was conducted on various immune subsets in peripheral blood mononuclear cells (PBMCs) from control and SLE subjects. Lectin binding was measured by multi-parameter flow cytometry in 18 manually gated subsets of T-cells, NK-cells, NKT-cells, B-cells, and monocytes in unstimulated resting state and also after 3-day activation. Stimulated pre-gated populations were subsequently clustered by FlowSOM algorithm based on lectin binding and activation markers, CD25 or HLA-DR.ResultsElevated AAL, SNA and CD25+/CD25- SNA binding ratio in certain stimulated SLE T-cell subsets correlated with SLE Disease Activity Index 2000 (SLEDAI-2K) scores. The significantly increased frequencies of activated AALlow Siglec-1low NK metaclusters in SLE also correlated with SLEDAI-2K indices. In SLE, activated double negative NKTs displayed significantly lower core fucosylation and CD25+/CD25- Siglec-1 binding ratio, negatively correlating with disease activity. The significantly enhanced AAL binding in resting SLE plasmablasts positively correlated with SLEDAI-2K scores.ConclusionAlterations in the glycosylation of immune cells in SLE correlate with disease severity, which might represent potential implications in the pathogenesis of SLE.

Targeted metabolomics combined with machine learning to identify and validate new biomarkers for early SLE diagnosis and disease activity.

The early diagnosis of systemic lupus erythematosus (SLE) and the assessment of disease activity progression remain a great challenge. Targeted metabolomics has great potential to identify new biomarkers of SLE. Serum from 44 healthy participants and 89 SLE patients were analyzed using HM400 high-throughput targeted metabolomics. Machine learning (ML) with seven learning models and trained the model several times iteratively selected the two best prediction model in a competitive way, which were independent validated by enzyme-linked immunosorbent (ELISA) with 90 SLE patients. In this study, 146 differential metabolites, most of them organic acids, amino acids, and bile acids, were detected between patients with initial SLE and healthy participants, and 8 potential biomarkers were found by intersection of ML and statistics (area under the curve [AUC] > 0.95) showing a significant positive correlation with clinical indicators. In addition, we identified and validated 2 potential biomarkers for SLE classification (P < 0.05, AUC > 0.775; N-Methyl-L-glutamic acid, L-2-aminobutyric acid) showing a significant correlation with the SLE Disease Activity Index. These differential metabolites were mainly involved in metabolic pathways, amino acid biosynthesis, 2-oxocarboxylic acid metabolism and other pathways. This study indicated that the tricarboxylic acid cycle might be associated with SLE drug therapy. We identified 8 diagnostic models biomarkers and 2 biomarkers that could be used to identify initial SLE and distinguish different activity degree, which will promote the development of new tools for the diagnosis and evaluation of SLE.

Prognostic Value of the 2019 EULAR/American College of Rheumatology Systemic Lupus Erythematosus Classification Criteria to Renal Response One Year After Treatment in a Cohort With Childhood-Onset Lupus Nephritis.

In 2019, the EULAR/American College of Rheumatology developed classification criteria for systemic lupus erythematosus (SLE). A positive correlation between summary score at diagnosis and SLE disease activity at five years has been noted in adult patients with lupus, but little is known among the pediatric population. We evaluated the prognostic value of higher summary scores and number of extrarenal domains at diagnosis (low/moderate number [1-5] vs high number [6-9]) to renal outcomes after one year of treatment in pediatric patients with lupus nephritis (LN). This retrospective, single-center cohort study included 74 pediatric patients with LN. Published pediatric renal response definitions were used for our outcome measure (no, partial, and complete response). Descriptive statistics were reported, and an ordinal logistic regression estimated adjusted odds ratios (ORs) for renal response including 95% confidence intervals (CIs). Patients with high extrarenal domains had OR 1.47 (95% CI 0.55-2.91) of having a complete renal response compared to patients with low/moderate domains. Patients with a summary score <30 had OR 1.31 (95% CI 0.50-3.44) of having a complete renal response relative to a summary score ≥30, though a larger proportion of patients with a summary score of ≥30 had no renal response after one year of treatment. More extrarenal domains at diagnosis did not have a statistically significant impact on renal response at one year, nor did a higher summary score. However, a larger portion of patients with a summary score <30 achieved complete renal response compared to patients with a score ≥30.

Methylprednisolone Pulses and Prolonged Remission in Systemic Lupus Erythematosus: A Propensity Score Analysis of the Longitudinal Lupus-Cruces-Bordeaux Inception Cohort.

The objective of this study was to analyze the effect of methylprednisolone pulses (MP), given during the first year after the diagnosis of systemic lupus erythematosus (SLE), in achieving prolonged remission according to the degree of lupus activity at presentation. We conducted an observational study of routine clinical care data from the Lupus-Cruces-Bordeaux cohort. The end point was prolonged remission (ie, during five consecutive yearly visits). The effect of MP on remission during the first year was analyzed in the whole cohort and according to the baseline Systemic Lupus Erythematosus Disease Activity Index 2000 score: <6, 6 to 12, and >12, reflecting mild, moderate, and severe activity, respectively. For adjustment, logistic regression with propensity score (PS) and other therapeutic covariates was performed. Two hundred thirty-three patients were included. Prolonged remission was achieved by 132 patients (57%). MP were associated with prolonged remission (PS-adjusted odds ratio [OR] 2.50, 95% confidence interval [CI] 1.04-623, P = 0.042). A strong clinical effect was seen among patients with moderate (adjusted OR 5.28, 95% CI 1.27-21.97, P = 0.022) and moderate-severe SLE activity (adjusted OR 4.07, 95% CI 1.11-14.82, P = 0.033). The administration of MP resulted in reduced average dosages of prednisone during the first year among patient with moderate (mean 6.6 vs 10.2 mg/day, P = 0.017) and severe activity (mean 14 vs 28 mg/day, P = 0.015). The odds of prolonged remission were increased by longer-term use of hydroxychloroquine (HCQ) and decreased by higher initial doses of prednisone. This study supports the use of MP to induce prolonged remission in patients with SLE, particularly in those with moderate and severe activity. The extended use of HCQ also contributes to achieve prolonged remission.

Immunogenicity, reactogenicity, and safety of two-dose adjuvanted herpes zoster subunit vaccine in patients with systemic lupus erythematosus in South Korea: a single-centre, randomised, double-blind, placebo-controlled trial

The adjuvanted herpes zoster subunit vaccine has shown good efficacy and safety in the general population. However, its effectiveness has not been comprehensively assessed in patients with systemic lupus erythematosus (SLE). This study aimed to evaluate the immunogenicity and safety of the adjuvanted herpes zoster subunit vaccine in patients with SLE. This single-centre, randomised, double-blind, placebo-controlled, trial was done at the rheumatology outpatient clinic at Seoul National University Hospital, South Korea. Patients (aged ≥19 years) with clinically stable SLE and previous exposure (≥4 weeks) to immunosuppressive drugs were randomly assigned (4:1) via a central interactive web response system to receive herpes zoster subunit vaccine or placebo (0·5 mL intramuscular injection) at weeks 0 and 8. Investigators and participants were masked to intervention and group assignment. Anti-glycoprotein E antibody titres and glycoprotein E-specific cell-mediated vaccine responses were evaluated at baseline and at week 8 after the first dose, and at week 4, week 26, and week 52 after the second dose using enzyme-linked immunosorbent assay and flow cytometry, respectively. Reactogenicity, SLE disease activity, including Systemic Lupus Erythematosus Disease Activity Index 2000 and British Isles Lupus Assessment Group-flare rate, were examined. The primary outcome was the proportion of patients with a positive humoral vaccine response 4 weeks after the second dose. The primary and safety analyses were done in a modified intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT06001606. Between June 14, and July 19, 2023, 65 patients with SLE were enrolled, of whom 52 were randomly assigned to the herpes zoster subunit vaccine and 13 to placebo. 49 patients in the vaccine group and 11 patients in the placebo group were included in the modified intention-to-treat population. 56 (93%) of 60 patients were women and four (7%) were men. Mean age was 48·7 years (SD 11·4). The proportion of participants with a humoral vaccine response at 4 weeks after the second dose was significantly higher in the vaccine group (48 [98%] of 49 participants) than the placebo group (none [0%] of 11 patients; p<0·0001). More patients in the vaccine group than placebo group reported injection site reactions (42 patients vs two patients), fever (ten vs none), and fatigue (26 vs two). There were no differences in Systemic Lupus Erythematosus Disease Activity Index 2000 and British Isles Lupus Assessment Group-flare rates between the groups. There were no treatment-related deaths. The herpes zoster subunit vaccine induces humoral and cellular immunity against herpes zoster with a good safety profile in patients with SLE. A larger study is warranted to assess the efficacy of vaccines to prevent herpes zoster in patients with SLE. Ministry of Science and ICT, The Government of the Republic of Korea.

Frequency of sarcopenia in Turkish women with systemic lupus erythematosus

ObjectiveThis study aimed to evaluate the prevalence of sarcopenia and its clinical significance in Turkish women with SLE, exploring the association between muscle mass, muscle strength and SLE disease activity.MethodsA...

Factors associated with adherence of cervical cancer screening in women with Systemic Lupus Erythematosus.

To determine cervical cancer screening rates and factors associated with decreased cervical cancer screening in women with systemic lupus erythematosus (SLE). We conducted a cross-sectional study that enrolled consecutive women (aged 21-64) with SLE. We collected demographics, clinical characteristics, constructs of the Health Beliefs Model (HBM) (i.e., susceptibility, severity, barriers, benefits, cues to action, and self-efficacy), and self-reported cervical cancer screening (confirmed with the electronic medical record). The primary outcome was adherence to cervical cancer screening according to current guidelines. Multivariable logistic regression models were used to examine the association between SLE disease activity and cervical cancer screening, and explore mediation effects from HBM constructs. We enrolled 130 women with SLE. The median age was 42 (IQR 32-52). The cervical cancer screening adherence rate was 61.5%. Women with high SLE disease activity were less likely to have cervical cancer screening versus those with low disease activity (OR 0.59, 0.39-0.89, p=0.01), which remained statistically significant after adjusting for baseline demographics and drug therapy in a multivariable model (OR 0.25, 95% CI 0.08-0.79, p=0.02). Regarding the HBM constructs, increased perceived barriers to cervical cancer screening (r=-0.30, p < 0.01) and decreased self-efficacy (r=-0.21, p=0.02) correlated with decreased cervical cancer screening. SLE patients with high disease activity undergo cervical cancer screening less frequently than those with low disease activated. Perceived barriers to cervical cancer screening are moderately correlated with decreased screening. These data highlight to need to develop strategies to increase cervical cancer screening in this high-risk patient population.

Indexes of skin activity and damage in patients with systemic lupus erythematosus – CLASI and R-CLASI

Introduction. Cutaneous Lupus Disease Area and Severity Index (CLASI) and its modified version, the Revised Cutaneous Lupus Erythematosus Disease Areas and Severity Index (R-CLASI) are tools for quantifying skin and mucosal lesions in patients with both cutaneous lupus erythematosus and its systemic variant. Evaluation of the scales of activity and skin damage in systemic lupus erythematosus (SLE) is associated with the need to stratify their quantitative characteristics. The Cutaneous Lupus Disease Area and Severity Index (CLASI) and its modified version the Revised Cutaneous Lupus Erythematosus Disease Area and Severity Index (R-CLASI) are a tool for quantifying skin and mucosal lesions in patients with both cutaneous lupus erythematosus (CLE) and its system version.Objective. To validate the indexes of objective assessment of skin activity and damage CLASI and R-CLASI in the Russian cohort of patients with systemic lupus erythematosus and compare it with dermatological assessments of the quality of life.Material and methods. The study included 55 patients with SLE with various types of skin and mucosal lesions, the median age was 30.0 [26.0; 40.0] years, the duration of the disease was 7.0 [3.0; 14.0] years. To assess the active (reversible) lesion and irreversible skin damage, the CLASI and R-CLASI indexes were used, for the general assessment of activity and damage in SLE, the SLEDAI-2K and SLICC/ACR DI were used.Results. The most common variant of skin lesions in patients with SLE is acute cutaneous lupus erythematosus (ACLE) – 45%, as well as alopecia, which occurs in 62% of cases. The median activity index for CLASI was 5.0 [2.0; 11.0], and R-CLASI was 7.0 [3.0; 18.0]; the median damage index for CLASI was 5.0 [2.0; 11.0], and R-CLASI was 2.0 [0.0; 7.0]. A significant relationship was revealed between the medians of CLASI and R-CLASI scores depending on the degree of activity according to SLEDAI-2K (Systemic Lupus Erythematosus Disease Activity Index) and the damage Index (DI) in SLE (SLICC/ACR DI, Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index) when recalculating these indexes only for skin and mucous lesions. According to the ROC analysis, the CLASI and R-CLASI skin activity and damage indices showed high sensitivity (CLASI activity index – 98%, R-CLASI – 93%, CLASI and R-CLASI damage index – 91%) and specificity (CLASI activity index – 64%, R-CLASI – 71%, CLASI and R-CLASI damage index – 86%).Conclusion. To assess the severity of skin and mucosal lesions in patients with SLE in the Russian Federation, it is reasonable to use the CLASI and R-CLASI indices. The CLASI and R-CLASI indices reflect the level of activity and severity of skin lesions, with higher values of these indices indicating more severe skin lesions and a significant impact on the overall well-being of SLE patients. Patients with high values of these indices often experience feelings of embarrassment, discomfort, difficulty in performing daily tasks, and limitations in social life. To assess the severity of skin and mucous lesions in patients with SLE in the Russian Federation, it is advisable to use the CLASI and R-CLASI indexes.

Risk factors for hospitalization in Mexican patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease that often requires hospitalization. Most hospitalizations are due to infections and/or disease activity, for which several risk factors have been described in non-Mestizo patients. To identify risk factors for hospitalization in patients with systemic lupus erythematosus (SLE). This was an observational case-control study of patients with SLE in San Luis Potosí, Mexico, evaluated from January 2019 to October 2020. We compared hospitalized lupus patients with non-hospitalized lupus patients. We used descriptive statistics and logistic regression to describe potential risk factors. Of a total of 202 patients, 89 (45.1%) were hospitalized; these patients were younger, had shorter disease duration, higher disease activity scores (systemic lupus erythematosus disease activity index-SLEDAI), and more accumulated damage than non-hospitalized patients. The primary reasons for hospitalization were disease activity (60.7%), kidney disease, infection, and drug toxicity (5.6%). Multivariate analysis revealed several risk factors associated with hospitalization, including elevated creatinine, C-reactive protein, neutrophil levels, and constitutional symptoms, while prolonged international normalized ratio (INR), longer stay in the intensive care unit (ICU), and vasopressor use were associated with mortality. The use of antimalarials was a protective factor against hospitalization. Survival analysis revealed that patients with hospital-acquired infections had a lower probability of survival. Disease activity was the most common reason for hospitalization; kidney, constitutional, and hematological factors were associated with hospitalization; and the use of antimalarial was a protective factor for hospitalization.

Addition of constitutional symptoms to the SLEDAI-2K improves overall disease activity assessment: A pilot study.

Constitutional symptoms (fatigue, lymphadenopathy, and weight loss) are not included in the SLE disease activity index-2000 (SLEDAI-2K). In this pilot study, we assessed the concurrent and construct validity of a revised SLEDAI-2K (SLED-R) that included these symptoms with the original SLEDAI-2K (SLED-O), using the physician global assessment of disease activity (PGA) as the reference. Our revised SLED-R substituted the SLED-O's fever descriptor with a constitutional descriptor that included fever, fatigue, lymphadenopathy, and/or weight loss. SLED-O, SLED-R, PGA and patient global assessment (PtGA) scores were collected prospectively. Bland-Altman correlations for repeated measures were calculated and Meng's z-test was used to compare correlations between dependent and overlapping correlation coefficients. Associations between constitutional symptoms and disease activity measures were analyzed using Mann-Whitney U, Kruskal-Wallis, Chi-square tests and repeated measures correlations. 1123 SLED-O, SLED-R, PGA, and 1066 PtGA were collected in 239 subjects. The new descriptor was scored in 45 subjects (18.8%) and 92 instances (8.1%), while the original descriptor, fever, was scored in only 4 subjects (1.7%) and 5 instances (0.4%). Mean SLED-O, PGA and PtGA scores were higher when the constitutional descriptor was scored versus not (p < .001). The correlation between SLED-R and PGA was marginally higher than between SLED-O and PGA (p < .001). Fatigue contributed most to this increase (p = .001) and associated with both higher PGA and PtGA scores (p < .001). Mean SLED-O and PGA scores were higher when ≥1 constitutional symptom(s) were scored versus not (p < .002). Correlations between PGA and PtGA when the new descriptor was scored versus not were similar (p = .860). The frequency of concordance between PGA and PtGA was lower when the new descriptor was scored (55%) versus not (72.5%), with PGA > PtGA when the new descriptor was scored (p < .001). The addition of constitutional symptoms to SLEDAI-2K, particularly fatigue, resulted in a marginal increase in its correlation with PGA, and new constitutional symptoms associated with higher SLED-O and PGA scores. As fatigue is subjective and difficult to attribute to SLE, its validity and inter-rater reliability in scoring remains uncertain. The clinical utility of SLED-R remains unclear, and further studies of its validity and reliability are needed.

Two-dimensional speckle-tracking echocardiography in left ventricular systolic function in patients with systemic lupus erythematosus.

To investigate whether two-dimensional speckle-tracking echocardiography (2DSTE) can be considered a criterion for early left ventricular (LV) systolic impairment in patients with systemic lupus erythematosus (SLE) and to further explore the association with each other. We included 38 patients with SLE and assessed the degree of disease activity according to the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) 2000 scoring criteria, together with 38 healthy controls who were matched by sex and age. Routine LV systolic function evaluation parameters were obtained by echocardiography as well as 2DSTE measurement of LV strain parameters to obtain global longitudinal strain (GLS) values, respectively. (I) On routine LV function parameters such as ejection fractions (EF) and left ventricular end-diastolic internal diameter (LVIDd), the SLE group and the control group did not reflect differences. In contrast, on the LV strain parameter obtained from 2DSTE measurements, the GLS values in all cardiac planes were lower in the SLE group than in the control group and showed statistically significant differences. (II) Correlation analysis showed that there was a correlation between SLEDAI and GLS, especially a meaningful correlation with GLS Avg and GLS A4C, with correlation coefficients of 0.35 and 0.47, respectively. The use of 2DSTE can detect early impaired LV systolic function in SLE patients, and GLS is progressively gaining attention as an indicator of subclinical myocardial injury and LV function in SLE patients. The correlation that exists between GLS and SLEDAI might contribute to a better assessment of cardiac involvement in SLE patients. Key Points • Cardiac involvement has become one of the major factors in the poor prognosis of SLE patients, which directly affects the mortality of SLE patients. Traditional echocardiography is difficult to detect early left ventricular function impairment, thus affecting clinicians' judgment and diagnosis. • 2DSTE can recognize subclinical myocardial injury in SLE patients at an early stage, and its derived strain parameters may be used as an indicator to evaluate myocardial involvement and reflect disease activity in SLE patients.

T cell expressions of aberrant gene signatures and Co-inhibitory receptors (Co-IRs) as predictors of renal damage and lupus disease activity

BackgroundSystemic lupus erythematosus (SLE) is distinguished by an extensive range of clinical heterogeneity with unpredictable disease flares and organ damage. This research investigates the potential of aberrant signatures on T cell genes, soluble Co-IRs/ligands, and Co-IRs expression on T cells as biomarkers for lupus disease parameters.MethodsComparative transcriptome profiling analysis of non-renal and end-stage renal disease (ESRD) phenotypes of SLE was performed using CD4 + and CD8 + cDNA microarrays of sorted T cells. Comparing the expression of Co-IRs on T cells and serum soluble mediators among healthy and SLE phenotypes.ResultsSLE patients with ESRD were downregulated CD38, PLEK, interferon-γ, CX3CR1, FGFBP2, and SLCO4C1 transcripts on CD4 + and CD8 + T cells simultaneously and NKG7, FCRL6, GZMB/H, FcγRIII, ITGAM, Fas ligand, TBX21, LYN, granulysin, CCL4L1, CMKLR1, HLA-DRβ, KIR2DL3, and KLRD1 in CD8 T cells. Pathway enrichment and PPI network analyses revealed that the overwhelming majority of Differentially Expressed Genes (DEGs) have been affiliated with novel cytotoxic, antigen presentation, and chemokine-cell migration signature pathways. CD8 + GZMK + T cells that are varied in nature, including CD161 + Mucosal-associated invariant T (MAIT) cells and CD161- aged-associated T (Taa) cells and CD161-GZMK + GZMB + T cells might account for a higher level of GZMK in CD8 + T cells associated with ESRD. SLE patients have higher TIGIT + , PD1 + , and lower CD127 + cell percentages on CD4 + T cells, higher TIM3 + , TIGIT + , HLA-DR + cell frequency, and lower MFI expression of CD127, CD160 in CD8 T cells. Co-IRs expression in T cells was correlated with soluble PD-1, PDL-2, and TIM3 levels, as well as SLE disease activity, clinical phenotypes, and immune-therapy responses.ConclusionThe signature of dysfunctional pathways defines a distinct immunity pattern in LN ESRD patients. Expression levels of Co-IRs in peripheral blood T cells and serum levels of soluble PD1/PDL-2/TIM3 can serve as biomarkers for evaluating clinical parameters and therapeutic responses.

Assessment of hematologic indices for diagnosis in juvenile systemic lupus erythematosus

IntroductionThe aim was to present effective approaches utilizing novel hematological parameters for early diagnosis of juvenile-onset systemic lupus erythematosus (jSLE).Material and methodsOur study at Ümraniye Training and Research Hospital involved a jSLE patient cohort from 2016 to 2022 and matched healthy controls aligning with sex and age. We use the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) for disease activity. Our approach was to analyze leukocyte, neutrophil, lymphocyte, monocyte, and platelet counts, along with ratios such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and monocyte-to-platelet ratio (MPR). We also explored novel indices: the systemic inflammatory index (SII), systemic inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI) to identify relationships between systemic indices and jSLE activity.ResultsUpon comparative analysis with the healthy control group, systemic lupus erythematosus (SLE) patients exhibited significantly elevated levels of the hematological parameters NLR, SII, and SIRI (&lt;i&gt;p&lt;/i&gt;-values: 0.010, 0.048, 0.025, respectively). Among SLE patients, neutrophil, lymphocyte, and platelet distribution width (PDW) values were notably higher, while hemoglobin, red blood cell distribution width (RDW), and procalcitonin (PCT) values were significantly lower. In comparison, C-reactive protein (CRP) and sedimentation values were markedly elevated in the SLE group in contrast to the healthy control cohort. Patients with significantly elevated disease activity had notably higher values of NLR (&lt;i&gt;p&lt;/i&gt; = 0.010) and SII (&lt;i&gt;p&lt;/i&gt; = 0.048). Among patients with positive anti-nuclear antibodies (ANA), elevated levels of NLR, SII, and SIRI were noted (&lt;i&gt;p&lt;/i&gt;-values: 0.018, 0.021, 0.035).ConclusionsIn this study, the novel hematological markers SII, SIRI, and AISI were found to effectively reflect inflammation in SLE patients, exhibit associations with high disease activity, and demonstrate heightened sensitivity in detecting cases with high disease activity.

Structural Brain MR Imaging Alterations in Patients with Systemic Lupus Erythematous with and without Neuropsychiatric Events.

Systemic lupus erythematosus is a complex autoimmune disease known for its diverse clinical manifestations, including neuropsychiatric systemic lupus erythematosus, which impacts a patient's quality of life. Our aim was to explore the relationships among brain MR imaging morphometric findings, neuropsychiatric events, and laboratory values in patients with systemic lupus erythematosus, shedding light on potential volumetric biomarkers and diagnostic indicators for neuropsychiatric systemic lupus erythematosus. Twenty-seven patients with systemic lupus erythematosus (14 with neuropsychiatric systemic lupus erythematosus, 13 with systemic lupus erythematosus), 24 women and 3 men (average age, 43 years, ranging from 21 to 62 years) were included in this cross-sectional study, along with 10 neuropsychiatric patients as controls. An MR imaging morphometric analysis, with the VolBrain online platform, to quantitatively assess brain structural features and their differences between patients with neuropsychiatric systemic lupus erythematosus and systemic lupus erythematosus, was performed. Correlations and differences between MR imaging morphometric findings and laboratory values, including disease activity scores, such as the Systemic Lupus Erythematosus Disease Activity Index and the Systemic Lupus International Collaborating Clinics Damage Index, were explored. An ordinary least squares regression analysis further explored the Systemic Lupus Erythematosus Disease Activity Index and Systemic Lupus International Collaborating Clinics Damage Index relationship with MR imaging features. For neuropsychiatric systemic lupus erythematosus and non-neuropsychiatric systemic lupus erythematosus, the brain regions with the largest difference in volumetric measurements were the insular central operculum volume (P value = .003) and the occipital cortex thickness (P = .003), which were lower in neuropsychiatric systemic lupus erythematosus. The partial correlation analysis showed that the most correlated morphometric features with neuropsychiatric systemic lupus erythematosus were subcallosal area thickness asymmetry (P < .001) and temporal pole thickness asymmetry (P = .011). The ordinary least squares regression analysis yielded an R 2 of 0.725 for the Systemic Lupus Erythematosus Disease Activity Index score, with calcarine cortex volume as a significant predictor, and an R 2 of 0.715 for the Systemic Lupus International Collaborating Clinics Damage Index score, with medial postcentral gyrus volume as a significant predictor. The MR imaging volumetric analysis, along with the correlation study and the ordinary least squares regression analysis, revealed significant differences in brain regions and their characteristics between patients with neuropsychiatric systemic lupus erythematosus and those with systemic lupus erythematosus, as well as between patients with different Systemic Lupus Erythematosus Disease Activity Index and Systemic Lupus International Collaborating Clinics Damage Index scores.

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.