Systemic Lupus Erythematosus Patients Research Articles

Glycolysis inhibition functionally reprograms T follicular helper cells and reverses lupus.

Systemic lupus erythematosus (SLE) is an autoimmune disease in which the production of pathogenic autoantibodies depends on T follicular helper (T FH ) cells. This study was designed to investigate the mechanisms by which inhibition of glycolysis with 2-deoxy-d-glucose (2DG) reduces the expansion of T FH cells and the associated autoantibody production in lupus-prone mice. Integrated cellular, transcriptomic, epigenetic and metabolic analyses showed that 2DG reversed the enhanced cell expansion and effector functions, as well as mitochondrial and lysosomal defects in lupus T FH cells, which include an increased chaperone-mediated autophagy induced by TLR7 activation. Importantly, adoptive transfer of 2DG-reprogrammed T FH cells protected lupus-prone mice from disease progression. Orthologs of genes responsive to 2DG in murine lupus T FH cells were overexpressed in the T FH cells of SLE patients, suggesting a therapeutic potential of targeting glycolysis to eliminate aberrant T FH cells and curb the production of autoantibodies inducing tissue damage.

Therapeutically targeting proinflammatory type I interferons in systemic lupus erythematosus: efficacy and insufficiency with a specific focus on lupus nephritis.

Type I interferons (IFN-Is) are important players in the immunopathogenesis of systemic lupus erythematosus (SLE). Pathogenic events in patients with SLE are potent triggers of IFN-I induction, yet IFN-I may induce or initiate the immunopathogenesis leading to these events. Because blocking IFN-I is effective in some clinical manifestations of SLE patients, concerns about the efficacy of anti-IFN-I therapy in patients with lupus nephritis remain. Tissues from kidney biopsies of patients with lupus nephritis revealed infiltration of various immune cells and activation of inflammatory signals; however, their correlation with renal damage is not clear, which raises serious concerns about how critical the role of IFN-I is among the potential contributors to the pathogenesis of lupus nephritis. This review addresses several issues related to the roles of IFN-I in SLE, especially in lupus nephritis, including (1) the contribution of IFN-I to the development and immunopathogenesis of SLE; (2) evidence supporting the association of IFN-I with lupus nephritis; (3) therapies targeting IFN-I and IFN-I downstream signaling molecules in SLE and lupus nephritis; (4) findings challenging the therapeutic benefits of anti-IFN-I in lupus nephritis; and (5) a perspective associated with anti-IFN-I biologics for lupus nephritis treatment. In addition to providing clear pictures of the roles of IFN-I in SLE, especially in lupus nephritis, this review addresses the lately published observations and clinical trials on this topic.

SLE patient satisfaction with care in Jordan: A single-center study.

Systemic Lupus Erythematosus (SLE) is a chronic multi-systemic autoimmune disease that mainly affects young females. SLE's chronicity and high level of complications yield frequent clinic visitations & hospital admissions, increasing the necessity to investigate the healthcare system and improve patient satisfaction and quality of life. This study aimed to understand SLE patients' points of view on the healthcare system in Jordan, especially given the chronic nature of the disease. With a clearer understanding, improvements can be made to benefit both the patients and the healthcare system. A cross-sectional study of 79 patients following up at the University of Jordan Hospital, rheumatology clinics were interviewed over the phone. The majority of patients were satisfied overall with the treatment services and medications as rated on a Likert scale of 1-5 (4.28 ± 1.01 and 4.19 ± 0.96, respectively) despite a quarter of patients complaining of adverse effects from the medications. The use of oral corticosteroids was significantly associated with a lower General Satisfaction Rate (p = 0.050), while high income (1000 Jordanian Dinars and above) and fatigue contributed to a lower Medication Satisfaction Rate (p = 0.016 and 0.000, respectively). A good physician-patient relationship was the most commonly cited reason for general satisfaction (73.4%) and was positively associated with the general (p = 0.000) and medication satisfaction (p = 0.004) rates. SLE patients perceived high satisfaction rates despite adverse effects and symptoms. These higher satisfaction rates were seen predominantly due to good physician-patient relationships.

ACHIEVING BETTER QUALITY OF LIFE THROUGH THE PROVISION OF SUPPLEMENTS, MEDICAL AIDS, AND COUNSELLING OF SLE PEDIATRIC PATIENTS AT RSSA MALANG

Introduction: Systemic lupus erythematosus (SLE) in children can interfere with their growth and social functioning and the treatment process is often hampered by low compliance and the unmet secondary needs of the patient. The aim of this community service activity is to improve the quality of life of patients by fulfilling their secondary needs and providing free consultation and education. Methods: This community service was carried out by educating and provide free consultation for 38 SLE pediatric patients accompanied by their parents directly at RSSA, monthly for 6 months, and we emphasise topics on management and healthy lifestyle for SLE patients. We also make this opportunity as a means of monitoring patient's condition which includes disease activity through SLEDAI Score, clinical symptoms, and psychosocial support, and we complete it by providing vitamin D supplements, sunblock, and wheelchairs. Results: All the subjects in this community service were 100% girls and 50% of them had active SLE status with various clinical manifestations. 79% of patients never took vitamin D supplements and all patients did not use sunblock. There were 3 patients with neurological disorders who needed a wheelchair. We provide their secondary needs to maximize the standard therapy we have been doing. After 6 months, there was a decrease in the number of patients who missed monthly controls, and a decrease in patients SLEDAI Score indicating that their lupus activity was appropriately controlled. Conclusion: Although rarely considered, the fulfillment of secondary needs in SLE patients such as vitamin D, sunblock, and wheelchairs for patients with mobility problems is very meaningful to them, which can optimize the main therapy given and make patients routinely attend monthly controls, because they find it helpful in terms of mobility. In addition, they do not need to buy vitamin D and sunblock themselves.

Simultaneous Multi-miRNA Detection in Urinary Small Extracellular Vesicles Using Target-Triggered Locked Hairpin DNA-Functionalized Au Nanoprobes for Systemic Lupus Erythematosus Diagnosis.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by multiorgan involvement and complex clinical manifestations, leading to cumbersome diagnostic processes. MicroRNAs (miRNAs) in small extracellular vesicles (sEVs) have emerged as promising biomarkers for liquid biopsy. Herein, we constructed a simple multi-miRNA detection platform based on target-triggered locked hairpin DNA-functionalized Au nanoprobes (AuNP@LH) as a simple and noninvasive tool for the diagnosis and classification of SLE. The nanoprobes were prepared by modifying locked hairpin DNA designed for target miRNAs on gold nanoparticles. In the presence of target miRNAs, target-triggered hairpin assembly amplification was induced, and then fluorophore-labeled bolt DNA was released, resulting in a fluorescence signal responsive to miRNA concentration. Benefiting from the enzyme-free amplification strategy, the limits of detection (LOD) of three miRNA biomarkers for SLE were 19 pM for microRNA-146a, 66 pM for microRNA-29c, and 19 pM for microRNA-150. The proposed probes have been successfully applied to simultaneously detect multiple miRNAs in urinary sEVs from patients diagnosed with SLE and healthy controls, which exhibited good practicability in SLE diagnosis with the area under curve (AUC) of the receiver characteristic curve reaching 1.00. Furthermore, SLE patients with different disease severity can be differentiated with 81.2% accuracy. Predictably, with the advantages of low cost, rapidity, high sensitivity, and noninvasiveness, our multi-miRNA detection platform is a potential tool for multiple miRNA analysis and related clinical applications.

Cutting Edge: Low-dose Recombinant IL-2 Treatment Prevents Autoantibody Responses in Systemic Lupus Erythematosus via Regulatory T Cell-independent Depletion of T Follicular Helper Cells.

The expansion of T follicular helper (Tfh) cells correlates with disease progression in human and murine systemic lupus erythematosus (SLE). Unfortunately, there are no therapies to deplete Tfh cells. Importantly, low-dose rIL-2-based immunotherapy shows potent immunosuppressive effects in SLE patients and lupus-prone mice, primarily attributed to the expansion of regulatory T cells (Tregs). However, IL-2 can also inhibit Tfh cell differentiation. In this study, we investigate the potential of low-dose rIL-2 to deplete Tfh cells and prevent autoantibody responses in SLE. Our data demonstrate that low-dose rIL-2 efficiently depletes autoreactive Tfh cells and prevents autoantibody responses in lupus-prone mice. Importantly, this immunosuppressive effect was independent of the presence of Tregs. The therapeutic potential of eliminating Tfh cells was confirmed by selectively deleting Tfh cells in lupus-prone mice. Our findings demonstrate the critical role of Tfh cells in promoting autoantibody responses and unveil, (to our knowledge), a novel Treg-independent immunosuppressive function of IL-2 in SLE.

Association between central corneal thickness and systemic lupus erythematosus: a cross-sectional study protocol.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease affecting multiple systems and classified under connective tissue disorders. Ocular involvement occurs in up to 30% of SLE cases, with the cornea being particularly susceptible to thinning due to immune-complex deposits and its predominantly type I collagen composition. This corneal thinning is clinically significant in glaucoma, where patients with reduced central corneal thickness (CCT) may have up to a threefold increased risk of developing glaucoma, as well as in refractive surgery. However, existing studies on CCT in SLE are limited and marked by substantial heterogeneity in methodology, technology, criteria, and participant numbers, resulting in conflicting findings. Based in our hypothesis that SLE-related corneal lysis may result in decreased CCT, this study aims to determine and compare the mean CCT values between SLE patients and healthy controls to obtain a more precise understanding of the potential relationship. A cross-sectional observational study will be conducted, enrolling SLE patients and age-and sex-matched healthy controls recruited from ophthalmology consultations. Exclusion criteria will be applied to rule out other corneal thinning risk factors. A pilot study estimated a minimum sample size of 34 participants per group. CCT measurements will be obtained using Zeiss HD Cirrus 5,000 optical coherence tomography (OCT) on a randomly selected eye, following concordance analysis using the Kappa index. Statistical analysis will include descriptive, bivariate, and multivariate methods. The study protocol was approved by the ethics committee. The cornea's vulnerability to thinning and lysis in SLE, which impacts CCT, is crucial for the accurate assessment of glaucoma, the leading cause of irreversible blindness worldwide and the second leading cause in Europe. Given that patients with reduced CCT are at a significantly higher risk of developing glaucoma, further research is necessary to understand the association between SLE and CCT. Our study aims to enhance methodological rigor compared to prior research by determining an appropriate sample size and exclusively enrolling SLE patients to increase participant homogeneity. If a significant difference in CCT between groups and an association between CCT and SLE are found, a prospective study will be considered.

Cyclosporine may reduce the risk of symptomatic COVID-19 in patients with systemic lupus erythematosus: a retrospective cohort study.

Our study indicated that cyclosporine may reduce the risk of symptomatic COVID-19 in systemic lupus erythematosus patients in spite of its immunosuppressive effects. This study provides a reference for clinical treatment strategies for AIIRD patients in the context of the long-term risk of SARS-CoV-2 infection.

Blood Growth Factor Levels in Patients with Systemic Lupus Erythematosus: High Neuregulin-1 Is Associated with Comorbid Cardiovascular Pathology.

Patients with systemic lupus erythematosus (SLE) are known to frequently suffer from comorbid cardiovascular diseases (CVDs). There are abundant data on cytokine levels and their role in the pathogenesis of SLE, while growth factors have received much less attention. The aim of this study was to analyze growth factor levels in SLE patients and their association with the presence of comorbid CVDs. The serum concentrations for the granulocyte-macrophage colony-stimulating factor (GM-CSF), nerve growth factor β (NGFβ), glial cell line-derived neurotrophic factor (GDNF), and neuregulin-1 β (NRG-1β) were determined in the SLE patients (n = 35) and healthy individuals (n = 38) by a Luminex multiplex assay. The NGFβ and NRG-1β concentrations were shown to be significantly higher in the total group of SLE patients (median [Q1-Q3]: 3.6 [1.3-4.5] and 52.5 [8.5-148], respectively) compared with the healthy individuals (2.9 [1.3-3.4] and 13.7 [4.4-42] ng/mL, respectively). The GM-CSF and GDNF levels did not differ. Interestingly, elevated NRG-1β levels were associated with the presence of CVDs, as SLE patients with CVDs had significantly higher NRG-1β levels (99 [22-242]) compared with the controls (13.7 [4.4-42]) and patients without CVDs (19 [9-80] ng/mL). The model for the binary classification of SLE patients with and without CVDs based on the NRG-1β level had an average predictive ability (AUC = 0.67). Thus, altered levels of growth factors may be associated with comorbid CVDs in SLE patients.

Evaluating the impact of type 2 diabetes mellitus on interstitial lung disease prevalence in patients with systemic lupus erythematosus: A national inpatient sample analysis.

Systemic lupus erythematosus (SLE) increases the risk of interstitial lung disease (ILD). SLE is also linked to an elevated risk of type 2 diabetes mellitus (T2DM). However, the impact of T2DM on ILD risk in patients with SLE is still unclear. This study aimed to compare the prevalence of ILD in patients with SLE based on the presence of T2DM (SLE + T2DM+) or its absence (SLE + T2DM-). This was a retrospective cohort study using the 2019-2020 National Inpatient Sample database. Adult SLE patients were identified and stratified by T2DM status. Comparable cohorts were created using propensity score matching, resulting in 10,532 patients in each cohort. Multivariate logistic regression assessed the association between T2DM and ILD. T2DM was associated with a lower prevalence of ILD in patients with SLE (OR 0.798, 95% CI: 0.695-0.918, p = .002), occurring in 371 (3.5%) patients with T2DM compared to 463 (4.4%) patients without T2DM. Specifically, this difference was mainly driven by pulmonary fibrosis, which was significantly less frequent in the T2DM group (1.3% vs 1.8%, OR 0.7, 95% CI: 0.560-0.875, p = .002). No differences were found in secondary outcomes, including death rates, length of hospital stay, ARDS, pneumothorax, pleural effusion, or pulmonary arterial hypertension. Our study suggests that T2DM significantly reduced ILD risk in patients with SLE, specifically diminishing pulmonary fibrosis prevalence. Further research should explore mechanisms for this protective association between T2DM and ILD development in SLE. These findings may guide management strategies for this vulnerable population.

The Interaction between Systemic Lupus Erythematosus and Cardiovascular Disease: Systematic Review

Patients diagnosed with systemic lupus erythematosus (SLE) face a much greater risk of morbidity and mortality from cardiovascular disease (CVD) when compared to the overall population. Despite numerous case reports and literature reviews delving into this connection, there are only a handful of systematic reviews that have specifically concentrated on this link. As a result, the objective of this systematic review is to assess the depth of the relationship between SLE and cardiovascular diseases. An extensive search was conducted primarily using PubMed and following PRISMA criteria. The search targeted English-language studies investigating the link between SLE and cardiovascular diseases. Clear inclusion and exclusion criteria were set to guarantee the quality and relevance of the evaluated research. The research encompassed a broad spectrum of studies from various global regions, with no particular emphasis on any specific gender or age. An evident trend revealed a significant proportion of SLE patients experiencing cardiovascular conditions. According to the findings of our investigation, in general, it was discovered that patients with SLE have a greater chance of developing CVD. It is essential to conduct additional research on the connection between identifiable SLE-specific risk factors that can be modified and the likelihood of developing CVD in order to bolster the creation of preventative and treatment measures.

Urine Extracellular Vesicles Size Subsets as Lupus Nephritis Biomarkers.

Systemic lupus erythematosus (SLE) is an autoimmune disorder that often leads to kidney injury, known as lupus nephritis (LN). Although renal biopsy is the primary way to diagnose LN, it is invasive and not practical for regular monitoring. As an alternative, several groups have proposed urinary extracellular vesicles (uEVs) as potential biomarkers for LN, as recent studies have shown their significance in reflecting kidney-related diseases. As a result, we developed a flow cytometry approach that allowed us to determine that LN patients exhibited a significantly higher total uEV concentration compared to SLE patients without kidney involvement. Additionally, an analysis of different-sized uEV subsets revealed that microvesicles ranging from 0.3 to 0.5 μm showed the most promise for distinguishing LN. These findings indicate that evaluating uEV concentration and size distribution could be a valuable diagnostic and monitoring tool for LN, pending further validation in more comprehensive studies.

Development and external validation of a prediction model for interstitial lung disease in systemic lupus erythematosus patients: A cross-sectional study

ObjectiveThe aim of this study is to develop and validate a nomogram that can assist clinicians in identifying female systemic lupus erythematosus (SLE) patients of reproductive age complicated with interstitial lung disease (ILD). MethodsClinical, laboratory data of SLE patients were first collected. Meteorological data were then gathered according to the geographical locations of the SLE patients. Diagnostic results, univariate logistic regression, elastic net regression, and multivariate logistic regression were used to screen for risk factors for female SLE patients of reproductive age complicated with ILD. A nomogram was constructed using these risk factors and was internally and externally validated through methods such as calculating the concordance index, plotting calibration curves, drawing receiver operating characteristic curves, and clinical decision curves. ResultsA total of 4798 SLE patients were included in this study, with 2488 patients in the development set and 2310 patients in the external validation set. The patients in the development set were randomly divided into a training set (N = 1742) and an internal testing set (N = 746) at a ratio of 7:3. Eight independent risk factors for ILD were identified, including APOB, APOA1, ALP, PLT, HCT, EOS-R, LYM-R, and age. The nomogram model was developed, and the areas under the receiver operating characteristic curve was 0.811 (0.748, 0.875), 0.820 (0.727,0.913), and 0.889 (0.869, 0.909) for the three sets, respectively. ConclusionWe established a nomogram model using easily accessible clinical and laboratory data to predict the probability of female SLE patients of reproductive age developing ILD.

Circulatory microRNAs and proinflammatory cytokines as predictors of lupus nephritis.

Lupus nephritis (LN) is one of the most prevalent severe organ manifestations of systemic lupus erythematosus (SLE), impacting 70% of SLE patients. MicroRNAs (miRNAs), are small non-coding RNA molecules which influence the expression of approximately one-third of human genes after the process of transcription. Dysregulation of miRNAs was documented in numerous disorders, including SLE and LN. Cytokines are the orchestrators of the immune response in autoimmune diseases. Our study aims to explore the variation in the levels of circulating miRNAs and proinflammatory cytokines as potential diagnostic biomarkers among LN and SLE patients without LN in comparison to controls. The study involved 20 LN patients, 20 SLE patients without LN, and 10 healthy controls. Serum levels of IL-12 and IL-21 in addition to miR-124, miR-146a, miR-199a, and miR-21 were assessed using the enzyme-linked immunosorbent assay (ELISA) for cytokines and quantitative real-time PCR for miRNAs. A significant downregulation in miR-124 (p<0.001) and a significant overexpression of miR-146a (p=0.005) were found in SLE patients without LN in comparison to controls. In comparison to SLE patients without LN and the control group, miR-199a, miR-21, and miR-146a were significantly upregulated in LN patients (p=<0.001) with high diagnostic values of these miRNAs in discriminating LN from SLE patients without LN according to Receiver operating curve (ROC) analysis. Logistic regression analysis revealed that only miR-199a is an independent predictor of LN (OR 1.69; 95% CI: 1.1-2.6). The expression of miR-124 was reduced in LN patients in comparison to the control but increased in LN patients in comparison to SLE patients without LN. However, there was no statistically significant difference in either scenario. In comparison to both SLE patients without LN and controls, LN patients exhibited the highest serum levels of IL-12 and IL-21, with no statistically significant difference. Regression analysis revealed that only miR-146a was associated with creatinine levels and SLEDAI score (p= 0.009 and 0.03, respectively), while miR-124 was associated with hemoglobin level (p=0.03). MiR-199a is an independent predictor for LN and might be used as a diagnostic biomarker for this disease. MiR-146a might play an important role in LN pathophysiology.

A retrospective evaluation of glucagon-like peptide-1 receptor agonists in systemic lupus erythematosus patients.

Glucagon-like peptide-1 receptor agonists (GLP1-RA) are an emerging class of medications with demonstrated promise in improving cardiometabolic outcomes. Whether these drugs may be useful in mitigating the cardiac risk associated with SLE remains unknown, and a recent case of drug induced lupus secondary to GLP1-RA use calls the safety of GLP1-RAs in SLE patients into question. Accordingly, this retrospective analysis was initiated to evaluate outcomes of GLP1-RAs in SLE. All patients in the NYU Lupus Cohort who had used a GLP1-RA were eligible for inclusion. Patient characteristics were assessed at baseline (most recent rheumatology visit prior to starting GLP1-RA), 1-4 months, and 6-10 months after GLP1-RA initiation. Of the 1211 patients in the cohort, only 24 had received a GLP1-RA. Six were excluded due to insufficient documentation regarding duration of medication use. Of the remaining 18 (median age 50), 17 (94%) were female and 9 (50%) were white. There was one mild-to-moderate flare at 6-10 months, but no patients accumulated new SLE criteria during the follow up period. Compared with baseline, median BMI was reduced by 3% at 1-4 months (p= 0.002) and 13% at 6-10 months (p= 0.001). Nine (50%) patients were initially denied insurance coverage for a GLP1-RA. While limited by a small sample size, this descriptive study showed that GLP1-RAs did not trigger flares above expected background rates and were associated with significantly decreased BMI. Future studies exploring the potential benefits of GLP1-RAs in patients with SLE are warranted.

Characterization of systemic lupus erythematosus subtypes using cluster analysis: insights from lymphocyte subpopulations.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease, in which lymphocyte subsets were dysregulated. Incorporating lymphocyte subpopulations in cluster analysis offers a pathway for personalized and precise treatment, targeting specific abnormalities for more effective management. We conducted Gaussian clustering analysis on clinical data, serological data, urine test results, and lymphocyte subpopulations for SLE patients hospitalized from September 2008 to December 2019. A total of 1863 SLE patients from Xi'Jing Hospital were included. After excluding those without complete assessments, 1281 patients underwent flow cytometry for lymphocyte subsets. Five SLE clusters emerged: Cluster 1 with severe kidney involvement, high SLEDAI scores, and infection rates, often accompanied by rashes and edema; cluster 2 with high urinary protein but better renal function; cluster 3 with normal lymphocyte count and low positive antibodies; cluster 4 with frequent psychiatric symptoms and pulmonary arterial hypertension (PAH); and cluster 5 with fever, arthritis, hematologic involvement, and high IgG levels despite decreased B cells. All enrolled SLE patients were ultimately categorized into five distinct clinical phenotype groups, with lymphocyte testing being meaningful for patient stratification. This finding shed light on the intricate heterogeneity of SLE, emphasizing the need for a personalized medicine approach. Targeting specific abnormalities in lymphocyte subsets holds promise for more effective and precise management of SLE. Key Points • A comprehensive analysis of SLE patients, including lymphocyte subpopulations, revealed five distinct clusters with varying clinical characteristics, emphasizing the heterogeneity of the disease. • This heterogeneity underscores the need for a personalized medicine approach in SLE management, targeting specific lymphocyte subset abnormalities for more effective and precise treatment.

An abnormal increase in CD26(-)CD28(-) cytotoxic effector CD4 and CD8 T cell populations in patients with systemic lupus erythematosus.

CD26 is a human T cell costimulatory molecule as well as a T cell subset marker, and increase of CD26+ T cells in inflamed tissues and peripheral blood has been reported in diverse autoimmune diseases. In contrast, our group has previously shown that levels of circulating CD26+ T cells are decreased in patients with systemic lupus erythematosus (SLE), although the role of reduced CD26 T cell surface expression in SLE pathology remains to be elucidated. In the present study, we conducted CD26-based T cell subset analyses utilizing peripheral blood mononuclear cells from 57 SLE patients and 31 healthy adult volunteers. We show that the increase in CD26(-) T cell population reflects the abnormal expansion of CD26(-)CD28(-) cytotoxic subsets of both CD8 T cells and CD4 T cells in SLE patients. Single cell RNA sequencing analysis of the CD26(-)CD28(-) CD4 and CD8 T cell populations reveals unique characteristics with similarities to natural killer T cells. In addition, the level of CD26(-)CD28(-) T cells is increased in some active stage SLE patients with renal manifestation. Meanwhile, effect of prednisolone treatment on these populations varies from patient to patient, with levels of these cytotoxic effector populations still being elevated in some inactive stage SLE patients. Taken together, our data suggest that analysis of these populations in SLE may be a useful tool to classify this markedly heterogeneous condition.

B-Cell Maturation Antigen (BCMA) as a Biomarker and Potential Treatment Target in Systemic Lupus Erythematosus.

The BAFF-APRIL system is crucial for the pathogenesis of systemic lupus erythematosus (SLE) by promoting B cell survival, differentiation and the maintenance of humoral autoimmunity. Here, we investigated the relationship of BCMA expression on B cell subsets with its ligands BAFF and APRIL, together with soluble BCMA, and with clinical and serologic variables in a cohort of 100 SLE patients (86 under conventional and 14 under belimumab therapy) and 30 healthy controls (HCs) using multicolor flow cytometry and ELISA. We found that BCMA expression in SLE patients was significantly increased on all B cell subsets compared to HCs, with all examined components of the BAFF-APRIL system being upregulated. BCMA expression was significantly increased on switched and unswitched memory B cells compared to naïve B cells, both in HCs and SLE. BCMA expression on B cells correlated with plasmablast frequencies, serum anti-dsDNA antibodies and complement consumption, while soluble BCMA correlated with plasmablast frequency, highlighting its potential as a clinical biomarker. Belimumab treatment significantly reduced BCMA expression on most B cell subsets and soluble TACI and contributed to the inhibition of almost the entire BAFF-APRIL system and restoration of B cell homeostasis. These results provide insights into the complex dysregulation of the BAFF-APRIL system in SLE and highlight the therapeutic potential of targeting its components, particularly BCMA, in addition to its use as a biomarker for disease activity.

Cytokine profiles and their correlation with clinical and blood parameters in rheumatoid arthritis and systemic lupus erythematosus.

The abnormal biological activity of cytokines and their imbalance are implicated in developing rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Cytokine levels were measured in RA and SLE patients and compared to healthy controls using the Wilcoxon rank sum test and Kruskal-Wallis test. The relationship between cytokine levels and blood and clinical parameters was assessed using Spearman's correlation test. Compared to healthy controls, both RA and SLE patients exhibited elevated levels of GM-CSF, CX3CL1, IFN-α2, IL-12p70, IL-17A, TNF-α, IL-1β, and IFN-γ, which is evidence of their shared inflammatory signature. IL-2 levels were elevated exclusively in RA patients, while MCP-1 and IL-10 were uniquely increased in SLE patients. Notably, TNF-α showed the most significant increase in SLE patients. IL-4 was elevated in SLE patients with nephritis, correlating with IL-6, IL-10, sCD40L, and IL-8, suggesting B cell involvement in lupus nephritis. The negative correlation between CX3CL1 and TNF-α with HDL in RA and SLE respectively, highlights the potential association of these inflammatory markers with cardiovascular risk. These findings underscore the complex cytokine interplay in RA and SLE. CX3CL1 emerges as a potential therapeutic target for RA, while TNF-α and IL-4 show promise as therapeutic targets for SLE.

Managing macrophage activation syndrome SLE: Clinical and therapeutic insights

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with frequent hematologic complications, including leukopenia, thrombocytopenia, autoimmune hemolytic anemia, and, in rare cases, macrophage activation syndrome (MAS). MAS, a severe hyperinflammatory condition, presents diagnostic challenges due to its overlap with SLE flares, infections, and drug-related adverse effects. This case report presents a 22-year-old female with SLE who experienced clinical deterioration following methotrexate initiation, manifesting as fever, pancytopenia, and transaminitis. Differential diagnoses were considered, including MAS, infection, and methotrexate toxicity. Prompt recognition and management with corticosteroids and immunoglobulins led to clinical improvement, underscoring the complexity of diagnosing and treating MAS in SLE patients.