Systemic Lupus Erythematosus Therapy Research Articles

Effect of combined use of prednisone and immunosuppressive therapy in patients with systemic lupus erythematosus, and its influence on incidence of adverse reactions

Purpose: To study the effect of combined use of prednisone and immunosuppressive therapy for systemic lupus erythematosus (SLE), and its impact on the incidence of adverse reactions.Methods: In total, 90 SLE patients treated in Longhui People's Hospital between January 2019 and January 2020 were included in this study, and assigned to receive either prednisone (control group) or immunosuppressive therapy and prednisone (study group) via the sealed envelope method. Outcome measures include immunoglobulin measured by enzyme-linked immunosorbent assay (ELISA), complement component 3 (C3) and C4 determined by immunoturbidimetric method, inflammatory factors such as INF-α, IL-10, and IL-6 levels, and the incidence of drug reactions.Results: After treatment, the treatment group had higher levels of immunoglobulin indices and C3 and C4 levels than the control group (p < 0.05). There were lower serum inflammatory factor levels in the treatment group than in the control group (p < 0.05). Prednisone and immunosuppressive therapy resulted in higher treatment effectiveness and lower SLEDAI scores, versus prednisone alone (p < 0.05).Conclusion: Prednisone and immunosuppressive therapy for SLE is safe, enhances treatment effectiveness, and improves clinical indicators in the patients. However, further trials are required prior to its application in clinical practice.

Impact of Belimumab on Organ Damage in Systemic Lupus Erythematosus.

Organ damage is a key determinant of poor long-term prognosis and early death in patients with systemic lupus erythematosus (SLE). Prevention of damage is a key treatment goal of the 2019 update of the European Alliance of Associations for Rheumatology (EULAR) recommendations for SLE management. Belimumab is a monoclonal antibody that inhibits B lymphocyte stimulator (BLyS) and is the only therapy approved for both SLE and lupus nephritis. Here, we review the clinical trial and real-world data on the effects of belimumab on organ damage in adult patients with SLE. Across 4 phase III studies, belimumab in combination with background SLE therapy demonstrated consistent reductions in key drivers of organ damage including disease activity, risk of new severe flares, and glucocorticoid exposure compared to background therapy alone. Long-term belimumab use in SLE also reduced organ damage progression measured by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index, as reported in open-label extension studies, and propensity score-matched comparative analyses to background therapy alone. Results from a clinical trial showed that in patients with active lupus nephritis, belimumab treatment improved renal response, reduced the risk of renal-related events, and impacted features related to kidney damage progression compared to background therapy alone. The decrease of organ damage accumulation observed with belimumab treatment in SLE, including lupus nephritis, suggest a disease-modifying effect.

Cell surface expression of human RP105 depends on N-glycosylation of MD-1.

For its cell surface expression, radioprotective 105 (RP105) - an orphan Toll-like receptor - must form a complex with a soluble glycoprotein called myeloid differentiation 1 (MD-1). The number of RP105-negative cells is significantly increased in patients with systemic lupus erythematosus (SLE); however, to elucidate the mechanism underlying this increase, how RP105 is expressed on the cell surface depending on MD-1 should be investigated. We demonstrated that RP105 exhibits two forms depending on MD-1 and its two N-glycosylation sites, N96 and N156. Cell surface expression of RP105 decreased in the presence of mutant MD-1 (N96Q/N156Q). Nonglycosylated MD-1 decreased the de novo cell surface expression of RP105 but not pre-expressed RP105. Thus, the N-glycans of MD-1 may represent targets for SLE therapy.

Mitochondrial impairment and repair in the pathogenesis of systemic lupus erythematosus.

Nucleic acid autoantibodies, increase type I interferon (IFN-α) levels, and immune cell hyperactivation are hallmarks of systemic lupus erythematosus (SLE). Notably, immune cell activation requires high level of cellular energy that is predominately generated by the mitochondria. Mitochondrial reactive oxygen species (mROS), the byproduct of mitochondrial energy generation, serves as an essential mediator to control the activation and differentiation of cells and regulate the antigenicity of oxidized nucleoids within the mitochondria. Recently, clinical trials on normalization of mitochondrial redox imbalance by mROS scavengers and those investigating the recovery of defective mitophagy have provided novel insights into SLE prophylaxis and therapy. However, the precise mechanism underlying the role of oxidative stress-related mitochondrial molecules in skewing the cell fate at the molecular level remains unclear. This review outlines distinctive mitochondrial functions and pathways that are involved in immune responses and systematically delineates how mitochondrial dysfunction contributes to SLE pathogenesis. In addition, we provide a comprehensive overview of damaged mitochondrial function and impaired metabolic pathways in adaptive and innate immune cells and lupus-induced organ tissues. Furthermore, we summarize the potential of current mitochondria-targeting drugs for SLE treatment. Developing novel therapeutic approaches to regulate mitochondrial oxidative stress is a promising endeavor in the search for effective treatments for systemic autoimmune diseases, particularly SLE.

Association of Clinical Manifestations of Systemic Lupus Erythematosus and Complementary Therapy Use in Taiwanese Female Patients: A Cross-Sectional Study.

Background and Objectives: Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease that affects predominantly women in the childbearing years. Patients may seek complementary therapies to manage their health and to reduce symptoms. However, to our knowledge, no studies have explored the association between clinical manifestations of SLE and complementary therapies. Therefore, this study aimed to investigate the association of complementary therapies with common clinical manifestations in Taiwanese female patients with SLE. Materials and Methods: A cross-sectional study was conducted at a regional teaching hospital in southern Taiwan. Outpatients from the rheumatology clinic who met the inclusion criteria were consecutively recruited. Demographic data, clinical manifestations of SLE, and types of complementary therapy use were determined using paper-based questionnaire. Multiple logistic regression analyses were conducted to investigate the use of complementary therapies associated with clinical manifestations of SLE. Results: Of the 317 female patients with SLE, 60.9% were 40 years or older. The five SLE clinical manifestations with the highest prevalence were Raynaud’s phenomenon (61.2%), photosensitivity (50.2%), Sjögren’s syndrome (28.4%), arthralgia and arthritis (22.1%), and renal involvement (14.5%). Multiple logistic regression analyses revealed that Raynaud’s phenomenon was significantly associated with fitness walking or strolling (adjusted odds ratio [aOR] 1.77; p = 0.027) and fish oil supplements (aOR 3.55, p < 0.001). Photosensitivity was significantly and inversely associated with the use of probiotics (aOR 0.49; p = 0.019). Renal involvement was significantly associated with the use of probiotics (aOR 2.43; p = 0.026) and visit to the Chinese medicine department in a hospital (aOR 3.14, p = 0.026). Conclusions: We found that different clinical manifestations of SLE were associated with the use of different complementary therapies. Health care providers should have up-to-date knowledge of common complementary therapies and be ready to provide evidence-based advice to patients with SLE.

A Tissue-Tended Mycophenolate-Modified Nanoparticle Alleviates Systemic Lupus Erythematosus in MRL/Lpr Mouse Model Mainly by Promoting Local M2-Like Macrophagocytes Polarization.

BackgroundMycophenolate mofetil (MMF), for which the bioactive metabolite is mycophenolic acid (MPA), is a frequently used immunosuppressant for systemic lupus erythematosus (SLE). However, its short half-life and poor biodistribution into cells and tissues hinder its clinical efficacy. Our dextran mycophenolate-based nanoparticles (MPA@Dex-MPA NPs) have greatly improved the pharmacokinetics of MMF/MPA. We here tested the therapeutic efficacy of MPA@Dex-MPA NPs against SLE and investigated the underlying mechanism.MethodsThe tissue and immune cell biodistributions of MPA@Dex-MPA NPs were traced using live fluorescence imaging system and flow cytometry, respectively. Serological proinflammatory mediators and kidney damage were detected to assess the efficacy of MPA@Dex-MPA NPs treatments of MRL/lpr lupus-prone mice. Immune cell changes in the kidney and spleen were further analyzed post-treatment via flow cytometry. Bone marrow-derived macrophages were used to investigate the potential mechanism.ResultsMPA@Dex-MPA NPs exhibited superior therapeutic efficacy and safety in the MRL/lpr mice using significantly lower administration dosage (one-fifth) and frequency (once/3 days) compared to MMF/MPA used in ordinary practice. The overall prognosis of the mice was improved as they showed lower levels of serological proinflammatory mediators. Moreover, kidney injury was alleviated with reduced pathological signs and decreased urine protein-creatinine ratio. Further investigations of the underlying mechanism revealed a preferential penetration and persistent retention of MPA@Dex-MPA NPs in the spleen and kidney, where they were mostly phagocytosed by macrophages. The macrophages were found to be polarized towards a CD206+ M2-like phenotype, with a downregulation of surface CD80 and CD40, and reduced TNF-α production in the spleen and kidney and in vitro. The expansion of T cells was also significantly inhibited in these two organs.ConclusionOur research improved the efficacy of MPA for MRL/lpr mice through synthesizing MPA@Dex-MPA NPs to enhance its tissue biodistribution and explored the possible mechanism, providing a promising strategy for SLE therapy.

The deacetylase SIRT2 contributes to autoimmune disease pathogenesis by modulating IL-17A and IL-2 transcription.

Aberrant IL-17A expression together with reduced IL-2 production by effector CD4+ T cells contributes to the pathogenesis of systemic lupus erythematosus (SLE). Here, we report that Sirtuin 2 (SIRT2), a member of the family of NAD+-dependent histone deacetylases, suppresses IL-2 production by CD4+ T cells while promoting their differentiation into Th17 cells. Mechanistically, we show that SIRT2 is responsible for the deacetylation of p70S6K, activation of the mTORC1/HIF-1α/RORγt pathway and induction of Th17-cell differentiation. Additionally, SIRT2 was shown to be responsible for the deacetylation of c-Jun and histones at the Il-2 gene, resulting in decreased IL-2 production. We found that the transcription factor inducible cAMP early repressor (ICER), which is overexpressed in T cells from people with SLE and lupus-prone mice, bound directly to the Sirt2 promoter and promoted its transcription. AK-7, a SIRT2 inhibitor, limited the ability of adoptively transferred antigen-specific CD4+ T cells to cause autoimmune encephalomyelitis in mice and limited disease in lupus-prone MRL/lpr mice. Finally, CD4+ T cells from SLE patients exhibited increased expression of SIRT2, and pharmacological inhibition of SIRT2 in primary CD4+ T cells from patients with SLE attenuated the ability of these cells to differentiate into Th17 cells and promoted the generation of IL-2-producing T cells. Collectively, these results suggest that SIRT2-mediated deacetylation is essential in the aberrant expression of IL-17A and IL-2 and that SIRT2 may be a promising molecular target for new SLE therapies.

Hydroxychloroquine Therapy and Serum Immunoglobulin Levels in Women with IgG Subclass Deficiency and Systemic Lupus Erythematosus, Sjögren Syndrome, and Rheumatoid Arthritis: A Retrospective Study.

Hydroxychloroquine (HCQ) therapy decreased immunoglobulin (Ig) levels in patients with Sjögren syndrome (SS) and rheumatoid arthritis (RA) in previous studies. We found no report of Ig levels of women with IgG subclass deficiency (IgGSD) and systemic lupus erythematosus (SLE), SS, or RA treated with HCQ. We retrospectively evaluated IgG, IgG subclass, IgA, and IgM levels and other characteristics of women at IgGSD diagnosis who did and did not take HCQ for SLE, SS, or RA. There were 132 women (48 subnormal IgG1 only, 49 combined subnormal IgG1/IgG3, and 35 subnormal IgG3 only). Mean age was 49 ± 13years. Twenty-two women with SLE, SS, RA, or combination thereof reported HCQ ≥ 200mg/day ≥ 6months. In each IgGSD subtype, median Ig levels of women who took HCQ were not significantly lower than those of women who did not take HCQ. Women with combined subnormal IgG1/IgG3 who took HCQ had greater median IgG2 than women who did not take HCQ (4.89g/L (range 4.43, 4.94) vs. 2.57g/L (1.21, 6.44), respectively; p = 0.0123). Regressions on IgG1, IgG2, and IgG3 revealed positive associations with HCQ therapy (p = 0.0043, 0.0037, and 0.0139, respectively). There were no significant Ig associations with age, SLE, SS, or RA as independent variables. HCQ therapy of SLE, SS, or RA in women with IgGSD was not associated with significantly lower IgG, IgG subclass, IgA, or IgM levels. IgG1, IgG2, and IgG3 were positively associated with HCQ therapy, after adjustment for other variables.

Genetic Polymorphisms and the Clinical Response to Systemic Lupus Erythematosus Treatment Towards Personalized Medicine.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by a broad spectrum of clinical manifestations, an aberrant autoimmune response to self-antigens, which affect organs and tissues. There are several immune-pathogenic pathways, but the exact one is still not well known unless it is related to genetics. SLE and other autoimmune diseases are known to be inseparable from genetic factors, not only pathogenesis but also regarding the response to therapy. Seventy-one human studies published in the last 10 years were collected. Research communications, thesis publication, reviews, expert opinions, and unrelated studies were excluded. Finally, 32 articles were included. A polymorphism that occurs on the genes related to drugs pharmacokinetic, such as CYP, OATP, ABC Transporter, UGT, GST or drug-target pharmacodynamics, such as FCGR, TLR, and BAFF, can change the level of gene expression or its activity, thereby causing a variation on the clinical response of the drugs. A study that summarizes gene polymorphisms influencing the response to SLE therapy is urgently needed for personalized medicine practices. Personalized medicine is an effort to provide individual therapy based on genetic profiles, and it gives better and more effective treatments for SLE and other autoimmune disease patients.

Preliminary study on anti-Müllerian hormone, antral follicle count, menstruation and lymphocyte subsets in systemic lupus erythematosus patients.

To investigate whether systemic lupus erythematosus (SLE) has a negative impact on the fertility of young women of reproductive age through SLE activity and therapy. This retrospective case-control study was conducted in 50 patients with SLE and 50 healthy controls who fulfilled the 1997 American College of Rheumatology criteria. Anti-Müllerian hormone (AMH) levels were measured, and ovarian volume (OV) and total antral follicle count (AFC) were assessed by transvaginal sonar in patients and in healthy controls. Analysis was carried out on the association of SLE disease activity with AMH, OV, and AFC. SLE patients had decreased levels of AMH, OV, and AFC, correlating with age, activity, and damage levels of SLE, displaying a negative consequence of SLE. In the SLE group, the CD4+ T cells and natural killer cells were significantly reduced (P<0.05). AMH levels and AFC were decreased in women with SLE with autoimmune activity and CD8+ T-cell activation; they can be used as useful markers and account for a high proportion of women with low ovarian reserve.

Tumor necrosis factor‑α in systemic lupus erythematosus: Structure, function and therapeutic implications (Review).

Tumor necrosis factor‑α (TNF‑α) is a pleiotropic pro‑inflammatory cytokine that contributes to the pathophysiology of several autoimmune diseases, such as multiple sclerosis, inflammatory bowel disease, rheumatoid arthritis, psoriatic arthritis and systemic lupus erythematosus (SLE). The specific role of TNF‑α in autoimmunity is not yet fully understood however, partially, in a complex disease such as SLE. Through the engagement of the TNF receptor1 (TNFR1) and TNF receptor2 (TNFR2), both the two variants, soluble and transmembrane TNF‑α, can exert multiple biological effects according to different settings. They can either function as immune regulators, impacting B‑, T‑ and dendritic cell activity, modulating the autoimmune response, or as pro‑inflammatory mediators, regulating the induction and maintenance of inflammatory processes in SLE. The present study reviews the dual role of TNF‑α, focusing on the different effects that TNF‑α may have on the pathogenesis of SLE. In addition, the efficacy and safety of anti‑TNF‑α therapies in preclinical and clinical trials SLE are discussed.

Biologic Agents and Other Emerging Therapies for Childhood SLE.

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease characterized by remissions and flares. Twenty percent of SLE presents in childhood where the course of SLE is often more severe with significant morbidity and mortality. Several biologic agents have been developed recently for the treatment of lupus, and although some have proven to be safe and efficacious, many have failed to demonstrate significant benefit in clinical trials. There continues to be a desperate need for safe, effective medications that target specific pathway abnormalities seen in SLE. This is an area of intense research that is changing clinical practice in the treatment of childhood SLE. In this article, we discuss the use of B-cell inhibitors, including belimumab and rituximab, as well as the anti-complement drug eculizumab. Promising treatments on the horizon include the jak-stat inhibitors as well as anifrolumab, which targets interferon. [Pediatr Ann. 2022;51(2):e63-e71.].

Treat-to-target in systemic lupus erythematosus: advancing towards its implementation.

The treat-to-target (T2T) concept has improved outcomes for patients with diabetes, hypertension and rheumatoid arthritis. This therapeutic strategy involves choosing a well-defined, relevant target, taking therapeutic steps, evaluating whether the target has been achieved, and taking action if it has not. The T2T principle has been embraced by systemic lupus erythematosus (SLE) experts, but measurable and achievable outcomes, and therapeutic options, are needed to make this approach possible in practice. Considerable evidence has been generated regarding meaningful 'state' outcomes for SLE. Low disease activity has been defined and studied, and the most aspirational goal, remission, has been defined by the Definition of Remission in SLE task force. By contrast, current therapeutic options in SLE are limited, and more effective and safer therapies are urgently needed. Fortunately, clinical trial activity in SLE has been unprecedented, and encouraging results have been seen for novel therapies, including biologic and small-molecule agents. Thus, with the expected advent of such treatments, it is likely that sufficiently diverse therapies for SLE will be available in the foreseeable future, allowing the routine implementation of T2T approaches in the care of patients with SLE.

Systemic Lupus Erythematosus: Targeted Literature Review of the Epidemiology, Current Treatment, and Disease Burden in the Asia Pacific Region

To understand the epidemiology, current treatment, and disease burden of systemic lupus erythematosus (SLE) in the Asia Pacific (APAC) region. A targeted literature review of published evidence on SLE in the APAC region was conducted, using the Medline database (2008-2018), conference proceedings, and other supplementary sources. The current review identified 70 studies conducted in China (n = 15), Japan (n = 13), Taiwan (n = 12), Korea (n = 9), Australia (n = 7), Hong Kong (n = 6), Singapore (n = 4), and multiple places within the APAC region (n = 4). Incidence rates (per 100,000 persons per year) ranged from 0.9-8.4, while prevalence rates ranged from 3.7-127 (per 100,000 persons); however, recent data were limited. Asian patients with SLE were reported to have higher disease severity, disease activity (higher SLE disease activity index scores), and organ damage accrual, along with increased morbidity, mortality, and susceptibility to renal involvement compared with other ethnicities in the APAC region. The risk of developing SLE is higher in the Asian population. Routinely used SLE therapies included belimumab, hydroxychloroquine, cyclophosphamide, tacrolimus, azathioprine, mycophenolate mofetil, and glucocorticoids; however, prescribing patterns varied across the region. Increased disease activity was associated with high economic burden and poor quality of life for SLE patients in the APAC region. SLE remains a disease with a significant unmet medical need for an innovative therapy that is well-tolerated and effective for patients in the APAC region. Further evidence is required to better characterize the disease and fully capture the burden and impact of SLE in the APAC region. This review has highlighted where there is a paucity of data from patients across the APAC region.

Promising Roles of Exosomal microRNAs in Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by the loss of immune tolerance. Lupus nephritis (LN) is still a major cause of the morbidity and mortality of SLE. In clinical practice, diagnosis, and therapy of SLE is complicated and challenging due to lack of ideal biomarkers. Exosomes could be detected from numerous kinds of biological fluids and their specific contents are considered as hallmarks of autoimmune diseases. The exosomal miRNA profiles of SLE/LN patients significantly differ from those of the healthy controls making them as attractive biomarkers for renal injury. Exosomes are considered as optimal delivery vehicles owing to their higher stable, minimal toxicity, lower immunogenicity features and specific target effects. Endogenous miRNAs can be functionally transferred by exosomes from donor cells to recipient cells, displaying their immunomodulatory effects. In addition, it has been confirmed that exosomal miRNAs could directly interact with Toll-like receptors (TLRs) signaling pathways to regulate NF-κB activation and the secretion of inflammatory cytokines. The present Review mainly focuses on the immunomodulatory effects of exosomal-miRNAs, the complex interplay between exosomes, miRNAs and TLR signaling pathways, and how the exosomal-miRNAs can become non-invasive diagnostic molecules and potential therapeutic strategies for the management of SLE.

Gut Microbiota Dysbiosis in Systemic Lupus Erythematosus: Novel Insights into Mechanisms and Promising Therapeutic Strategies.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that was traditionally thought to be closely related to genetic and environmental risk factors. Although treatment options for SLE with hormones, immunosuppressants, and biologic drugs are now available, the rates of clinical response and functional remission of these drugs are still not satisfactory. Currently, emerging evidence suggests that gut microbiota dysbiosis may play crucial roles in the occurrence and development of SLE, and manipulation of targeting the gut microbiota holds great promises for the successful treatment of SLE. The possible mechanisms of gut microbiota dysbiosis in SLE have not yet been well identified to date, although they may include molecular mimicry, impaired intestinal barrier function and leaky gut, bacterial biofilms, intestinal specific pathogen infection, gender bias, intestinal epithelial cells autophagy, and extracellular vesicles and microRNAs. Potential therapies for modulating gut microbiota in SLE include oral antibiotic therapy, fecal microbiota transplantation, glucocorticoid therapy, regulation of intestinal epithelial cells autophagy, extracellular vesicle-derived miRNA therapy, mesenchymal stem cell therapy, and vaccination. This review summarizes novel insights into the mechanisms of microbiota dysbiosis in SLE and promising therapeutic strategies, which may help improve our understanding of the pathogenesis of SLE and provide novel therapies for SLE.

Nucleic Acid-Sensing and Interferon-Inducible Pathways Show Differential Methylation in MZ Twins Discordant for Lupus and Overexpression in Independent Lupus Samples: Implications for Pathogenic Mechanism and Drug Targeting.

Systemic lupus erythematosus (SLE) is a chronic, multisystem, autoimmune inflammatory disease with genomic and non-genomic contributions to risk. We hypothesize that epigenetic factors are a significant contributor to SLE risk and may be informative for identifying pathogenic mechanisms and therapeutic targets. To test this hypothesis while controlling for genetic background, we performed an epigenome-wide analysis of DNA methylation in genomic DNA from whole blood in three pairs of female monozygotic (MZ) twins of European ancestry, discordant for SLE. Results were replicated on the same array in four cell types from a set of four Danish female MZ twin pairs discordant for SLE. Genes implicated by the epigenetic analyses were then evaluated in 10 independent SLE gene expression datasets from the Gene Expression Omnibus (GEO). There were 59 differentially methylated loci between unaffected and affected MZ twins in whole blood, including 11 novel loci. All but two of these loci were hypomethylated in the SLE twins relative to the unaffected twins. The genes harboring these hypomethylated loci exhibited increased expression in multiple independent datasets of SLE patients. This pattern was largely consistent regardless of disease activity, cell type, or renal tissue type. The genes proximal to CpGs exhibiting differential methylation (DM) in the SLE-discordant MZ twins and exhibiting differential expression (DE) in independent SLE GEO cohorts (DM-DE genes) clustered into two pathways: the nucleic acid-sensing pathway and the type I interferon pathway. The DM-DE genes were also informatically queried for potential gene–drug interactions, yielding a list of 41 drugs including a known SLE therapy. The DM-DE genes delineate two important biologic pathways that are not only reflective of the heterogeneity of SLE but may also correlate with distinct IFN responses that depend on the source, type, and location of nucleic acid molecules and the activated receptors in individual patients. Cell- and tissue-specific analyses will be critical to the understanding of genetic factors dysregulating the nucleic acid-sensing and IFN pathways and whether these factors could be appropriate targets for therapeutic intervention.

Metabolic Analysis of Potential Key Genes Associated with Systemic Lupus Erythematosus Using Liquid Chromatography-Mass Spectrometry.

The biological mechanism underlying the pathogenesis of systemic lupus erythematosus (SLE) remains unclear. In this study, we found 21 proteins upregulated and 38 proteins downregulated by SLE relative to normal protein metabolism in our samples using liquid chromatography-mass spectrometry. By PPI network analysis, we identified 9 key proteins of SLE, including AHSG, VWF, IGF1, ORM2, ORM1, SERPINA1, IGF2, IGFBP3, and LEP. In addition, we identified 4569 differentially expressed metabolites in SLE sera, including 1145 reduced metabolites and 3424 induced metabolites. Bioinformatics analysis showed that protein alterations in SLE were associated with modulation of multiple immune pathways, TP53 signaling, and AMPK signaling. In addition, we found altered metabolites associated with valine, leucine, and isoleucine biosynthesis; one carbon pool by folate; tyrosine metabolism; arginine and proline metabolism; glycine, serine, and threonine metabolism; limonene and pinene degradation; tryptophan metabolism; caffeine metabolism; vitamin B6 metabolism. We also constructed differently expressed protein-metabolite network to reveal the interaction among differently expressed proteins and metabolites in SLE. A total of 481 proteins and 327 metabolites were included in this network. Although the role of altered metabolites and proteins in the diagnosis and therapy of SLE needs to be further investigated, the present study may provide new insights into the role of metabolites in SLE.

Mesenchymal Stem Cell Therapy: Hope for Patients With Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. Although previous studies have demonstrated that SLE is related to the imbalance of cells in the immune system, including B cells, T cells, and dendritic cells, etc., the mechanisms underlying SLE pathogenesis remain unclear. Therefore, effective and low side-effect therapies for SLE are lacking. Recently, mesenchymal stem cell (MSC) therapy for autoimmune diseases, particularly SLE, has gained increasing attention. This therapy can improve the signs and symptoms of refractory SLE by promoting the proliferation of Th2 and Treg cells and inhibiting the activity of Th1, Th17, and B cells, etc. However, MSC therapy is also reported ineffective in some patients with SLE, which may be related to MSC- or patient-derived factors. Therefore, the therapeutic effects of MSCs should be further confirmed. This review summarizes the status of MSC therapy in refractory SLE treatment and potential reasons for the ineffectiveness of MSC therapy from three perspectives. We propose various MSC modification methods that may be beneficial in enhancing the immunosuppression of MSCs in SLE. However, their safety and protective effects in patients with SLE still need to be confirmed by further experimental and clinical evidence.

Clinical relevance of T follicular helper cells in systemic lupus erythematosus

ABSTRACT Introduction T helper cells regulate a variety of immune responses and are involved in the pathogenesis of infection, allergy and autoimmune diseases. T follicular helper (Tfh) cells, which induce B cell maturation, play an important role in the production of the extremely diverse autoantibodies found in systemic lupus erythematosus (SLE). Area covered We provide an overview of the plasticity and diversity of Tfh cells in humans and their involvement in the pathology and pathogenesis of SLE. Our review outlines the potential of Tfh cells as a therapeutic target for SLE. Expert opinion Tfh cells are involved in the pathogenesis of SLE based on their plasticity and diversity. Tfh cell differentiation and function are variably regulated by cytokines (IL-12, interferons, IL-2, etc), co-stimulatory molecules (ICOS, CD40L, OX40, etc), and intracellular signals (JAK-STAT, etc). Elucidation of the mechanisms underlying Tfh cell differentiation and function may lead to the development of new therapies for SLE.