Systemic Lupus Erythematosus Disease Activity Index Research Articles

#1532 Correlation between TNF-alpha, IL-4 and IL-6 levels and vitamin D in patients with SLE lupus nephritis

Abstract Background and Aims Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease characterized by multisystem organ damage and high titers of autoantibodies to a number of nuclear and cytoplasmic antigens. Numerous abnormalities of the cytokine network have been observed in patients suffering from SLE. However, the relationship between cytokines and vitamin D in damage to the kidneys and various organs has not been studied enough. Aim To determine whether interleukin-6.4 (IL-6.4) and tumor necrosis factor (TNF-alpha) levels correlate with vitamin D deficiency in patients with SLE/FN. Method We determined the levels of TNF-alpha, IL-6, IL-4 and vitamin D in the blood of patients with SLE/FN in 108 people. Results Levels of TNF-alpha, IL-4 and IL-6 were higher in SLE/FN patients with vitamin D deficiency. Further analysis showed that this association was dependent on an inverse correlation (P = 0.017, r = ‒0, 49) for IL-6, (P = 0.023, r = ‒0.42) for IL-4, and (P = 0.76, r = ‒0.243) for TNF-alpha. The average level of TNF-alpha was (3.2+/-6.92 pg/ml), IL-4 and IL-6 showed results (2.13+/-8.72 pg/ml) and 5.02+ /-7.22 pg/ml) respectively for patients with vitamin D deficiency, while it was for IL-6, for IL-4 (3.5+/-6.43 pg/ml) and TNF- alpha (4.33+/-8.61 pg/ml) for patients with normal concentrations of vitamin D in the blood and IL-6, (1.02+/-5.1 pg/ml), IL-4 (2.13+/- 6.4 pg/ml), TNF-alpha (1.45+/-5.28 pg/ml), for the healthy control group, respectively. The difference was statistically significant (P = 0.002). We found a significant positive correlation between TNF-alpha, IL-4 and IL-6 and low vitamin D levels, respectively, and with the SLE Disease Activity Index (SLEDAI). (r = +0.743 and +0.772, respectively). Conclusion Increased levels of IL-4, IL-6 and TNF-alpha may influence the development and progression of nephritis in patients with SLE, in addition, the production of large amounts of IL-4, IL-6 and TNF-alpha correlates with low levels of vitamin D in the blood.

BCMA-CD19 compound CAR T cells for systemic lupus erythematosus: a phase 1 open-label clinical trial

ObjectivesThis study aims to evaluate the safety and efficacy of BCMA-CD19 compound chimeric antigen receptor T cells (cCAR) to dual reset the humoral and B cell immune system in patients...

Efficacy and safety of telitacicept therapy in systemic lupus erythematosus with hematological involvement.

To evaluate the efficacy and safety of telitacicept in SLE patients specifically with hematological involvement. A total of 22 patients with SLE and hematological involvement were included in this study. These patients received telitacicept in addition to standard therapy. We compared their demographic characteristics, clinical manifestations, and laboratory indicators before and after the administration of telitacicept. A total of 22 patients received telitacicept treatment for a median duration of 10.4months (ranging from 6 to 19months). Following telitacicept therapy, significant improvements were observed in various parameters compared to baseline. Specifically, white blood cell count increased from (3.98 ± 1.80) 109/L to (6.70 ± 2.47) 109/L, (P = 0.002), hemoglobin levels increased from (100 ± 19) g/L to (125 ± 22) g/L, (P < 0.001), and platelet count increased from (83 ± 60) 109/L to (161 ± 81) 109/L, (P = 0.004). SLE Disease Activity Index (SLEDAI) scores decreased from 12(5,15) to 0(0,4), (P < 0.001). Additionally, C3 and C4 levels showed improvement. Telitacicept treatment also resulted in a significant reduction in serum IgG levels and daily prednisone dosage. Only one adverse event (4.5%) was reported during the treatment, which was a urinary tract infection. The combination of telitacicept and standard treatment demonstrated significant improvements in anemia, as well as increased leukocyte and platelet levels in patients with SLE and hematological involvement. Importantly, the observed adverse events were manageable and controllable. Key Points • Telitacicept effectively improves anemia, clinical outcomes, and increases leukocyte and platelet counts. • Treatment with telitacicept leads to decreased levels of lgG, IgA, anti-dsDNA, and SLEDAI scores, while serum complement C3 and C4 returned to normal. • During the follow-up period there were observed changes in individual parameters, clinical symptoms, and organ involvement, all without significant adverse events.

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 &gt; 0.200, P &lt; .05) with ESR, CRP and SLEDAI-2K while Neut-Y (measures nucleic acid content by sideward fluorescence) showed a significant negative correlation ( r &gt; 0.200, P &lt; .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.

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.

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.

Cell 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). Evaluation 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. Elevated 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. Alterations 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

BackgroundThe 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. MethodsSerum 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. ResultsIn 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. ConclusionThis 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.

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...

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.

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.

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.