Treatment Of SLE Research Articles

Dexamethasone and IFN-γ primed mesenchymal stem cells conditioned media immunomodulates aberrant NETosis in SLE via PGE2 and IDO

BackgroundSystemic Lupus Erythematosus (SLE) is characterized by dysregulated immune responses, with neutrophil extracellular traps (NETs) playing a significant role. NETs are recognized by autoantibodies in SLE patients, exacerbating pathology. Both excessive NET formation and impaired degradation contribute to SLE pathophysiology.ObjectiveTo investigate the immunomodulatory effects of Dexamethasone-primed Wharton’s jelly (WJ) derived MSCs CM (DW) and IFN-γ-primed WJ-MSCs-CM (IW) on NETosis and associated protein markers in SLE patients’ LPS or ribonucleoprotein immune complexes (RNP ICs) induced neutrophils and in pristane induced lupus (PIL) model. And to elucidate the mechanism involved therein.MethodsWe investigated the immunomodulatory effects of DW and IW on NETosis in SLE. Utilizing ex vivo and in vivo models, we assessed the impact of preconditioned media on NET formation and associated protein markers neutrophil elastase (NE), citrullinated histone (citH3), myeloperoxidase (MPO), cytoplasmic and mitochondrial ROS production. We also examined the involvement of key immunomodulatory factors present in DW and IW, including prostaglandin E2 (PGE2), indoleamine 2,3-dioxygenase (IDO), and transforming growth factor-beta (TGF-β).ResultsPreconditioned media effectively suppressed NETosis and reduced ROS generation in SLE neutrophils, indicating their immunomodulatory potential. Inhibition studies implicated IDO and PGE2 in mediating this effect. Combined treatment with DW or IW together with hydroxychloroquine (HCQ) demonstrated superior efficacy over HCQ alone, a standard SLE medication. In PIL mouse model, DW and IW treatments reduced NETosis, ROS generation, as evidenced by decreased NET-associated protein expression in vital organs.ConclusionOur study highlights the multifaceted impact of IW and DW on NETosis, ROS dynamics, and lupus severity in SLE. These findings underscore the potential of preconditioned media for the development of targeted, personalized approaches for SLE treatment.

Inhibitory effect of hydroxychloroquine on glucocorticoid‐induced osteoporosis in lupus therapy

AbstractObjectivesSystemic lupus erythematosus (SLE) is a chronic and severe autoimmune disease characterised by persistent inflammation. Hydroxychloroquine (HCQ) and glucocorticoids (GCs) are the primary agents commonly used in combination as the first‐line treatment for SLE. Nevertheless, the specific mechanisms responsible for the effectiveness of this combined therapy with HCQ and GCs have not been fully elucidated. This study aimed to reveal the mechanism behind combined HCQ and GC treatment in lupus.MethodsAn SLE IgG‐induced inflammation model was used to investigate the anti‐inflammatory effects of HCQ and dexamethasone (DXM). A glucocorticoid‐induced osteoporosis (GIOP) model was used to investigate the inhibitory effect of HCQ on osteoclastogenesis. Inflammation was assessed by haematoxylin and eosin staining. Bone metabolism was determined structurally via microcomputer tomography and in bone marrow‐derived osteoclast cultures.ResultsAn SLE IgG‐induced inflammation model demonstrated that HCQ could not ameliorate inflammation alone but could enhance the anti‐inflammatory effect of GCs by decreasing the expression of FcγRI on macrophages. HCQ inhibited osteoclastogenesis induced by GCs and RANKL by upregulating nuclear factor erythroid 2‐related factor 2 and limiting reactive oxygen species formation, which mitigated GC‐induced bone loss.ConclusionThe results indicate that HCQ improved the anti‐inflammatory effects of GCs and inhibits the osteoclastogenesis in experimental lupus. This study offers valuable insights into the mechanisms underlying the combined treatment of lupus with HCQ and GCs.

Oral magnesium reduces levels of pathogenic autoantibodies and skin disease in murine lupus

BackgroundSystemic Lupus Erythematosus (SLE) has a strong genetic susceptibility, but little is known about the impact of diet on disease severity. The Western diet is typically deficient in magnesium (Mg), and given the immunomodulatory effects of Mg, we hypothesized that the low Mg intake increases disease risk and that increasing Mg intake would reduce severity of murine lupus. Here, we placed 12-week old MRL/lpr female lupus mice on a normal (Mg500) or a high (Mg2800) Mg diet for 9 weeks. Urine and blood were collected during the study for quantification of urinary albumin, BUN, anti-dsDNA antibodies, and immune phenotyping.ResultsMRL/lpr lupus mice on high Mg2800 diet had significantly fewer skin lesions and less severe skin histology score, and reduced levels of pathogenic anti-dsDNA antibodies, compared with the Mg500 group (143.8±75.0 vs. 47.4±36.2 × 106U/ml; P < 0.05). The high Mg2800 group had a nearly two-fold increase in the percentage of CD4+FOXP3+ Treg cells compared to controls (19.9±5.4 vs. 11.4±5.5%; P < 0.05). Treg percentages inversely correlated with the concentration of anti-dsDNA. None of the mice developed arthritis during the observation period and there were no significant differences in weight, proteinuria, BUN or kidney histology.ConclusionIn conclusion, oral supplementation of Mg has a protective effect in a murine lupus model and may represent an inexpensive and safe adjuvant in the treatment of SLE.

Prioritizing drug targets in systemic lupus erythematosus from a genetic perspective: a druggable genome-wide Mendelian randomization study

ObjectivesSystemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with an unsatisfactory state of treatment. We aim to explore novel targets for SLE from a genetic standpoint. MethodsCis-expression quantitative trait loci (eQTLs) for whole blood from 31,684 samples provided by the eQTLGen Consortium as well as two large SLE cohorts were utilized for screening and validating genes causally associated with SLE. Colocalization analysis was employed to further investigate whether changes in the expression of risk genes, as indicated by GWAS signals, influence the occurrence and development of SLE. Targets identified for drug development were evaluated for potential side effects using a phenome-wide association study (PheWAS). Based on the multiple databases, we explored the interactions between drugs and genes for drug prediction and the assessment of current medications.ResultsThe analysis comprised 5427 druggable genes in total. The two-sample Mendelian randomization (MR) in the discovery phase identified 20 genes causally associated with SLE and validated 8 genes in the replication phase. Colocalization analysis ultimately identified five genes (BLK, HIST1H3H, HSPA1A, IL12A, NEU1) with PPH4 > 0.8. PheWAS further indicated that drugs acting on BLK and IL12A are less likely to have potential side effects, while HSPA1A and NEU1 were associated with other traits. Four genes (BLK, HSPA1A, IL12A, NEU1) have been targeted for drug development in autoimmune diseases and other conditions.Conclusions.This study identified five genes as therapeutic targets for SLE. Repurposing and developing drugs targeting these genes is anticipated to improve the existing treatment state for SLE.Key Points• We identified five gene targets of priority for the treatment of SLE, with BLK and IL12A indicating fewer side effects.• Among the existing drugs that target these candidate genes, Ustekinumab, Ebdarokimab, and Briakinumab (targeting the IL12 gene) and CD24FC (targeting HSPA1A) may potentially be repurposed for the treatment of SLE.

Gut microbiota regulation of T lymphocyte subsets during systemic lupus erythematosus

BackgroundSystemic lupus erythematosus (SLE) is an autoimmune disease characterized by disturbance of pro-inflammatory and anti-inflammatory lymphocytes. Growing evidence shown that gut microbiota participated in the occurrence and development of SLE by affecting the differentiation and function of intestinal immune cells. The purpose of this study was to investigate the changes of gut microbiota in SLE and judge its associations with peripheral T lymphocytes.MethodsA total of 19 SLE patients and 16 HCs were enrolled in this study. Flow cytometry was used to detect the number of peripheral T lymphocyte subsets, and 16 s rRNA was used to detect the relative abundance of gut microbiota. Analyzed the correlation between gut microbiota with SLEDAI, ESR, ds-DNA and complement. SPSS26.0 software was used to analyze the experimental data. Mann–Whitney U test was applied to compare T lymphocyte subsets. Spearman analysis was used for calculating correlation.ResultsCompared with HCs, the proportions of Tregs (P = 0.001), Tfh cells (P = 0.018) and Naïve CD4 + T cells (P = 0.004) significantly decreased in SLE patients, and proportions of Th17 cells (P = 0.020) and γδT cells (P = 0.018) increased in SLE. The diversity of SLE patients were significantly decreased. Addition, there were 11 species of flora were discovered to be distinctly different in SLE group (P < 0.05). In the correlation analysis of SLE, Tregs were positively correlated with Ruminococcus2 (P = 0.042), Th17 cells were positively correlated with Megamonas (P = 0.009), γδT cells were positively correlated with Megamonas (P = 0.003) and Streptococcus (P = 0.004), Tfh cells were positively correlated with Bacteroides (P = 0.040), and Th1 cells were negatively correlated with Bifidobacterium (P = 0.005). As for clinical indicators, the level of Tregs was negatively correlated with ESR (P = 0.031), but not with C3 and C4, and the remaining cells were not significantly correlated with ESR, C3 and C4.ConclusionGut microbiota and T lymphocyte subsets of SLE changed and related to each other, which may break the immune balance and affect the occurrence and development of SLE. Therefore, it is necessary to pay attention to the changes of gut microbiota and provide new ideas for the treatment of SLE.

Inhibition of receptor interacting protein kinase-1 (RIPK1) in the treatment of murine lupus

ObjectiveSystemic lupus erythematosus (SLE) is a type of autoimmune disease that involves multiple organs involved as well as cytokine dysregulation. The treatment of SLE is still challenging due to the...

Investigating the therapeutic mechanism of Jiedu-Quyu-Ziyin Fang on systemic lupus erythematosus through the ERα-miRNA-TLR7 immune axis

Jiedu-Quyu-Ziyin Fang (JQZF) is a formula that has been empirically used for the treatment of SLE in clinical practice. JQZF has become an approved hospital prescription in China. Fifteen MRL/lpr mice were randomly divided into three groups: Model, JQZF, and JQZF + GC, with five mice in each group. Five MRL/MPJ mice were used as the Blank group. After 8 weeks of administration, peripheral blood serum was collected to detect anti-dsDNA antibodies and complement C3 levels. Spleen B cells were collected to detect the expression of TLR7 and NF-κBp65 mRNA, and correlation analysis was performed. Transcriptome sequencing analysis was also performed on spleen B cells. Further, key miRNA and key gene mRNA expression were detected by RT-qPCR, and key protein expression levels were detected by Western blot method. Bioinformatics methods predicted that ESR1 is a key target of JQZF action on SLE, hsa-miR-146a-5p is one of the key miRNAs, and KEGG pathway analysis showed that NF-κB signaling pathway is its key signaling pathway. Transcriptome sequencing of MRL/lpr mouse spleen B cells revealed that the differential genes between the JQZF and Model groups were enriched in Toll-like receptor signaling pathway, NF-κB signaling pathway, Estrogen signaling pathway, etc. Animal studies show that JQZF treatment significantly boosts serum C3 and lowers anti-dsDNA antibodies (P < 0.01). On the molecular level, JQZF suppresses TLR7 and NF-κBp65 mRNA in spleen B cells, with TLR7 mRNA positively linked to anti-dsDNA titers and negatively to serum C3. Further cellular work demonstrates that JQZF reverses the increased IRAK1 and TRAF6 expression seen after miR146a inhibition. Additionally, post-ERα inhibition, JQZF continues to upregulate miR146a and more significantly reduces TLR7 mRNA expression (P < 0.01), pointing to ERα′s pivotal role in the miR146a-TLR7 axis. These results indicate JQZF alleviates SLE by adjusting the ERα-miR146a-TLR7 loop, showcasing its mechanism and therapeutic potential for SLE.

Exploring risk factors for autoimmune diseases complicated by non-hodgkin lymphoma through regulatory T cell immune-related traits: a Mendelian randomization study.

The effect of immune cells on autoimmune diseases (ADs) complicated by non-Hodgkin lymphoma (NHL) has been widely recognized, but a causal relationship between regulatory T cell (Treg) immune traits and ADs complicated by NHL remains debated. Aggregate data for 84 Treg-related immune traits were downloaded from the Genome-Wide Association Study (GWAS) catalog, and GWAS data for diffuse large B-cell lymphoma (DLBCL; n=315243), follicular lymphoma (FL; n=325831), sjögren's syndrome (SS; n=402090), rheumatoid arthritis (RA; n=276465), dermatopolymyositis (DM; n=311640), psoriasis (n=407876), atopic dermatitis (AD; n=382254), ulcerative colitis (UC; n=411317), crohn's disease(CD; n=411973) and systemic lupus erythematosus (SLE; n=307587) were downloaded from the FinnGen database. The inverse variance weighting (IVW) method was mainly used to infer any causal association between Treg-related immune traits and DLBCL, FL, SS, DM, RA, Psoriasis, AD, UC, CD and SLE, supplemented by MR-Egger, weighted median, simple mode, and weighted mode. Moreover, we performed sensitivity analyses to assess the validity of the causal relationships. There was a potential genetic predisposition association identified between CD39+ CD8br AC, CD39+ CD8br % T cell, and the risk of DLBCL (OR=1.51, p<0.001; OR=1.25, p=0.001) (adjusted FDR<0.1). Genetic prediction revealed potential associations between CD25++ CD8br AC, CD28- CD25++ CD8br % T cell, CD39+ CD8br % CD8br, and the risk of FL (OR=1.13, p=0.022; OR=1.28, p=0.042; OR=0.90, p=0.016) (adjusted FDR>0.1). Furthermore, SLE and CD exhibited a genetically predicted potential association with the CD39+ CD8+ Tregs subset. SS and DM were possibly associated with an increase in the quantity of the CD4+ Tregs subset; RA may have reduced the quantity of the CD39+ CD8+ Tregs subset, although no causal relationship was identified. Sensitivity analyses supported the robustness of our findings. There existed a genetically predicted potential association between the CD39+ CD8+ Tregs subset and the risk of DLBCL, while SLE and CD were genetically predicted to be potentially associated with the CD39+ CD8+ Tregs subset. The CD39+ CD8+ Tregs subset potentially aided in the clinical diagnosis and treatment of SLE or CD complicated by DLBCL.

Disruption of memory B-celltrafficking by belimumab in patients with systemic lupus erythematosus.

Autoreactive memory B cells (MBCs) contribute to chronic and progressive courses in autoimmune diseases like SLE. The efficacy of belimumab (BEL), the first approved biologic treatment for SLE and LN, is generally attributed to depletion of activated naïve B cells and inhibition of B-cellactivation. BEL's effect on MBCs is currently unexplained. We performed an in-depth cellular and transcriptomic analysis of BEL's impact on the blood MBC compartment in patients with SLE. A retrospective meta-analysis was conducted, pooling flow cytometry data from four randomized trials involving 1245 patients with SLE treated with intravenous BEL or placebo. Then, extensive MBC phenotyping was performed using high-sensitivity flow cytometry in patients with mild/moderate SLE and severe SLE/LN treated with subcutaneous BEL. Finally, transcriptomic characterization of surging MBCs was performed by single-cell RNA sequencing. In BEL-treated patients, a significant increase in circulating MBCs, in a broad range of MBC subsets, was established at week 2, gradually returning to baseline by week 52. The increase was most prominent in patients with higher SLE disease activity, serologically active patients and patients aged ≤18 years. MBCs had a non-proliferating phenotype with a prominent decrease in activation status and downregulation of numerous migration genes. Upon BEL initiation, an increase of MBCs was firmly established. In the small cohort investigated, circulating MBCs were de-activated, non-proliferative and demonstrated characteristics of disrupted lymphocyte trafficking, expanding on our understanding of the therapeutic mechanism of B-cell-activating factor inhibition by BEL. ClinicalTrials.gov, http://clinicaltrials.gov, NCT00071487, NCT00410384, NCT01632241, NCT01649765, NCT03312907, NCT03747159.

Unveiling the nexus: Decoding interactions between regulated cell death and systemic lupus erythematosus pathogenesis for innovative therapeutic avenues

AbstractSystemic lupus erythematosus (SLE) is characterized by disruptions in cell death pathways and impaired clearance of apoptotic cells, resulting in immune dysregulation and tissue damage. This review explores the complex interplay of regulated cell death (RCD) mechanisms, including apoptosis, necroptosis, pyroptosis, NETosis, autophagy, and ferroptosis, in the pathogenesis of SLE. These pathways release autoantigens and danger signals, triggering autoimmune reactions and inflammation. Six various RCDs have mutual associates to support immune dysregulation and are associated with SLE. Apoptosis intrinsically induces immune tolerance by packaging dying cells into immunologically inert fragments. Deficiencies in apoptotic clearance will result in impaired tolerance. Necroptosis, pyroptosis, NETosis, and ferroptosis lead to cell membrane destruction, production of intracellular immunostimulatory components, and triggering a strong inflammatory immune reaction. Abnormal autophagic activity affects the development, differentiation, function, and metabolism of many immune cell subpopulations. Investigating the interconnections between cell death pathways and SLE sheds light on the disease's underlying mechanisms and provides opportunities for novel therapeutic interventions. The convergence of precision medicine and innovative strategies targeting these intricate pathways holds promise for expanding the landscape of SLE treatment.

The mechanism of Langchuangding in treatment of systemic lupus erythematosus via modulating TLR7-IRF7-IFNα pathway

ObjectSystemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by aberrant activity of the immune system. Plasmacytoid dendritic cells (pDCs) which the main producer of activated type I interferon, are related to SLE disease activity. To investigate the mechanism of Langchuangding (LCD) improving SLE based on TLR7-IRF7-IFNα pathway. MethodsSLE patients were randomly divided into Chinese medicine combined with western medicine (CWM) group and western medicine (WM) group, to observe the effect of LCD. The percent of pDCs in peripheral blood of SLE patients were detected by flow cytometry, and the influence of LCD on gene expression in SLE patients were detected by gene microarray. Mouse bone marrow cells were differentiated into dendritic like cells (DLC), then divided into Blank, immune complex (IC), LCD and dexamethasone (DXM) group. Employed RT-qPCR to detect MyD88, and IRF7 mRNA, and western blotting to determinate TLR7, MyD88, and p-IRF7 proteins. The IFNα in SLE patients were detected by enzyme-linked immunosorbent assay (ELISA). Employ dual luciferase to observe the interferon stimulated response element (ISRE) gene. ResultspDCs in WM group was higher than that of CWM group. The plasma IFNα in CWM group was significantly lower than that in WM group. The gene microarray showed that the gene expression of IFNα related signaling pathway in peripheral blood mononuclear cell (PBMC) and genes related to activation and proliferation of immune cells were down-regulated after LCD treatment. The DLCs MyD88, and IRF7 mRNA were down-regulated, TLR7, MyD88, and p-IRF7 proteins were significantly reduced, and the supernatant IFNα was significantly decreased in LCD group. LCD were mildly inhibited activation of ISRE in 293T cells. ConclusionsIn certain degree, LCD is beneficial to SLE patients. LCD therapy SLE may be through TLR7 signaling pathway, and IRF7 may be a promising therapeutic target for the treatment of SLE.

Potential role of RhoA GTPase regulation in type interferon signaling in systemic lupus erythematosus

ObjectiveSystemic lupus erythematosus (SLE) is an autoimmune disorder characterized by abnormal activation of the type I interferon (IFN) pathway, which results in tissue inflammation and organ damage. We explored the role of the RhoA GTPase in the type I IFN activation pathway to provide a potential basis for targeting GTPase signaling for the treatment of SLE.MethodsTotal RNA was extracted from peripheral blood mononuclear cells (PBMCs) of SLE patients and healthy controls, and the mRNA expression levels of RhoA and IFN-stimulated genes were measured by SYBR Green quantitative reverse transcriptase-polymerase chain reaction. IFN-a-stimulated response element (ISRE)-luciferase reporter gene assays and Western blotting were conducted to assess the biologic function of RhoA. An enzyme-linked immunoassay (ELISA) measured C-X-C motif chemokine ligand 10 (CXCL10) protein expression.ResultsOur studies demonstrate that the expression of RhoA in the PBMCs of SLE subjects was significantly higher than in healthy controls and positively correlated with type I IFN scores and type I IFN-stimulated gene (ISGs) expression levels. SiRNA-mediated knockdown of RhoA and the RhoA/ROCK inhibitor Y27632 reduced the activity of the type I IFN-induced ISRE, the signal transducer and activator of transcription 1 (STAT-1) phosphorylation, and the expression of CXCL10 and 2′-5′-oligoadenylate synthetase 1 (OAS1). Finally, we verified that Y27632 could significantly down-regulate the OAS1 and CXCL10 expression levels in the PBMCs of SLE patients.ConclusionOur study shows that RhoA positively regulates the activation of the type I IFN response pathway. Reducing the expression level of RhoA inhibits the abnormal activation of the type I IFN system, and the RhoA/ROCK inhibitor Y27632 decreases aberrant type I IFN signaling in SLE PBMCs, suggesting the possibility of targeting the RhoA GTPase for the treatment of SLE.

Quality of Life in Systemic Lupus Erythematosus and Other Chronic Diseases: Highlighting the Amplified Impact of Depressive Episodes.

Extensive research has explored SLE's impact on health-related quality of life (H-QoL), especially its connection with mental wellbeing. Recent evidence indicates that depressive syndromes significantly affect H-QoL in SLE. This study aims to quantify SLE's impact on H-QoL, accounting for comorbid depressive episodes through case-control studies. A case-control study was conducted with SLE patients (meeting the ACR/EULAR 2019 criteria of age ≥ 18). The control group was chosen from a community database. H-QoL was measured with the SF-12 questionnaire, and PHQ-9 was used to assess depressive episodes. SLE significantly worsened H-QoL with an attributable burden of 5.37 ± 4.46. When compared to other chronic diseases, only multiple sclerosis had a worse impact on H-QoL. Major depressive episodes had a significant impact on SLE patients' H-QoL, with an attributable burden of 9.43 ± 5.10, similar to its impact on solid cancers but greater than its impact on other diseases. SLE has a comparable impact on QoL to serious chronic disorders. Concomitant depressive episodes notably worsened SLE patients' QoL, exceeding other conditions, similar to solid tumors. This underscores the significance of addressing mood disorders in SLE patients. Given the influence of mood disorders on SLE outcomes, early identification and treatment are crucial.

Rituximab as an effective add-on maintenance therapy for disease activities in childhood-onset systemic lupus erythematosus

ObjectivesSystemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease that can result in high morbidity if not treated. This retrospective study aimed to evaluate the outcomes of rituximab treatment...

EULAR 2023 recommendations for SLE treatment: synopsis for the management of lupus nephritis— the European Renal Association (ERA) — Immunonephrology Working Group (ERA-IWG) perspective

No abstract

Lupus mice derived mesenchymal stromal cells: Beneficial or detrimental on SLE disease outcome

BackgroundSystemic Lupus Erythematosus (SLE) is a chronic autoimmune disease characterized by the presence of autoantibodies against nuclear genes, deposition of immune complexes, and autoimmune T cells, through which, tissue damage would ultimately occur. Furthermore, loss of immune tolerance and imbalance of Th1/Th2 cells in addition to Th17/Treg are contributed to the pathogenesis of SLE. Mesenchymal stromal cells (MSCs) infusion is a potential therapy for SLE disease. Despite a majority of SLE patients achieving clinical remission after allogeneic MSC infusion from healthy individuals, SLE patients have less benefited from autologous MSC infusion, justifying the probable compromised function of SLE patients-derived MSCs. In this study, we aim to further investigate the potential immunoregulatory mechanisms in which mesenchymal stromal cells derived from pristane-induced lupus mice, following injection into healthy and lupus mice, exert their possible effects on the lupus process. Method40 female Balb/c mice aged 3 weeks were purchased and randomly divided into six groups. First, lupus disease was induced into the lupus groups by intraperitoneal injection of pristane and then the mice were surveyed for 6 months. The body weight, anti-dsDNA autoantibody levels, serum creatinine, and Blood Urea Nitrogen (BUN) levels were measured in two-month intervals. After 6 months, the group of lupus mice was sacrificed, and lupus MSCs were isolated. Two months later, cultured lupus MSCs were intravenously injected into two groups of healthy and lupus mice. After two months, the mice were euthanized and the kidneys of each group were examined histologically by hematoxylin & eosin (H&E) staining and the immunofluorescence method was also performed to evaluate IgG and C3 deposition. The frequency of splenic Th1, Th2, Th17, and Treg cells was measured by flow cytometry. Moreover, the cytokine levels of IFN-γ, IL-4, IL-17, and TGF-β in sera were measured by ELISA method. ResultsOur results showed that the induction of lupus disease by pristane in Balb/c mice caused the formation of lipogranuloma, increased levels of anti-dsDNA autoantibodies, and impaired renal function in all pristane-induced lupus groups. In addition, the injection of lupus mesenchymal stromal cells (L-MSC) into healthy and lupus mice led to a further rise in anti-dsDNA serum levels, IgG and C3 deposition, and further dysfunction of mice renal tissue. Also, the flow cytometry results implicated that compared to the control groups, splenic Th1, Th2, and Th17 inflammatory cell subtypes and their secreted cytokines (IFN-γ, IL-4, and IL-17) in the sera of healthy and lupus mice were increased after the intake of L-MSC. Additionally, the splenic Treg cells were also significantly increased in the lupus mice receiving L-MSC. However, a decrease in serum levels of TGF-β cytokine was observed in healthy and lupus mice following L-MSC injection. In contrast, the lupus mice receiving healthy mesenchymal stem cells (H-MSC) manifested opposite results. ConclusionIn a nutshell, our results suggest that although allogeneic MSCs are encouraging candidates for SLE treatment, syngeneic MSCs may not be eligible for treating SLE patients due to their defects in regulating the immune system in addition to their capability in promoting inflammation which would consequently worsen the SLE disease status.

Efficacy of baricitinib for the treatment of systemic lupus erythematosus patients: A meta-analysis of randomized controlled trials.

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by abnormal autoantibody production, inflammation, and organ damage. Most SLE treatment strategies aim to induce remission or reduce disease activity while avoiding flares. Baricitinib has been used effectively to manage various inflammatory diseases, and some randomized controlled trials (RCT) have shown that it is beneficial in treating SLE. The current study aims to assess the efficacy of baricitinib in treating SLE patients. Various databases such as PubMed, Scopus, and Science Direct were searched to obtain eligible studies for the present meta-analysis. Data such as baseline characteristics of patients, doses of the baricitinib, follow-up duration, and treatment outcome in the form of SLE responder index-4 (SRI-4) and lupus low disease activity state (LLDAS) were extracted. Combined odds ratio, 95% confidence interval, and probability values were calculated to study the efficacy of baricitinib in treating SLE patients. A p-value less than .05 was taken as significant. Comprehensive meta-analysis v3 was used for all analyses. Three articles were found eligible for the present meta-analysis comprising 614 patients with placebo, 614 SLE patients receiving 4 mg, and 621 patients with 2 mg of baricitinib. Meta-analysis revealed a beneficial effect of 4 mg baricitinib in SLE patients compared to placebo, as measured by an increase in the SRI-4 (p = .006, OR = 1.370) and LLDAS (p = .083, OR = 1.252) rates. In contrast to the placebo group, however, patients receiving 2 mg of baricitinib exhibited no significant improvement. The trial sequential analysis revealed the need for additional RCTs to determine the role of baricitinib in treating SLE patients. In treating SLE patients, administrating a higher dose of baricitinib (4 mg) may be effective. However, additional RCTs in different populations with larger sample sizes are required to validate our findings.

Efficacy and safety of baricitinib in treatment of systemic lupus erythematosus: a systematic review and meta-analysis

BackgroundSLE is an autoimmune disease marked by broad immunological dysregulation and multi-system inflammation. Baricitinib is one of the novel treatments for SLE. We conducted this meta-analysis to evaluate its safety and effectiveness in treating SLE.MethodWe looked for all published randomized controlled trials in PubMed, Scopus, Web of Science, and Cochrane and included all RCTs comparing baricitinib and placebo in the treatment of SLE. Review Manager 5.4 program was used for data analysis.ResultsThree trials with a total of 1849 individuals were included. Participants in the baricitinib group were significantly more likely to attain SRI-4 response than those in the placebo group [RR = 1.11, 95% CI (1.02, 1.21), P = 0.01]. Additionally, baricitinib performed better than the placebo in terms of reduction of ≥ 4 points from baseline in SLEDAI-2 K score [RR = 1.13, 95% CI (1.04, 1.22), P = 0.004]. In terms of SLEDAI-2 K remission of arthritis or rash, baricitinib was also superior to placebo [RR = 1.08, 95% CI (1.00, 1.17), P = 0.04]. Treatment-emergent adverse events did not differ significantly [RR = 1.01, 95% CI (0.97, 1.05), P = 0.61].ConclusionBaricitinib is potentially safe and effective in the treatment of SLE. It has successfully met the study’s primary endpoint and some secondary endpoints highlighting its potential to improve the outcomes of SLE. Despite achieving an SRI-4 response, glucocorticoids sparing and some other secondary outcomes weren’t reached by baricitinib.

EULAR 2023 recommendations for SLE treatment: synopsis for the management of lupus nephritis: the European Renal Association-Immunonephrology Working Group (ERA-IWG) perspective.

EULAR 2023 recommendations for SLE treatment: synopsis for the management of lupus nephritis: the European Renal Association-Immunonephrology Working Group (ERA-IWG) perspective.

Immunotherapeutic approaches for systemic lupus erythematosus: early overview and future potential.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease. Current SLE therapies include immunosuppressants, antimalarial drugs, non-steroidal anti-inflammatory drugs (NSAIDs), and corticosteroids, but these treatments can cause substantial toxicities to organs and may not be effective for all patients. In recent years, significant progress has been made in the treatment of SLE using immunotherapy, including Benlysta and Saphnelo. These advances in immunotherapy hold promise for SLE patients, providing new therapeutic options that may offer better clinical benefit and effectiveness. Simultaneously, several new biological therapies focusing on cytokines, peptides, targeted antibodies, and cell-based approaches are under clinical evaluation and have shown immense potential for the treatment of SLE. However, the complexity of SLE immunopathogenesis and disease heterogeneity present significant challenges in the development of effective immunological therapies. This review aims to discuss past experiences and understanding of diverse immunological targeting therapies for SLE and highlight future perspectives for the development of novel immunological therapies.