Target In Systemic Lupus Erythematosus Research Articles

Exploring the Mechanism of Curcumin-mediated Photodynamic Therapy for Systemic Lupus Erythematosus Based on Network Pharmacology

ObjectiveTo explore the potential therapeutic targets, this study explored possible molecular mechanism of curcumin photodynamic therapy for systemic lupus erythematosus using network pharmacology. MethodsThe potential targets for systemic lupus erythematosus upon curcumin and photodynamic treatment were predicted using Venny2.1 online analysis platform, followed by GO functional annotation and KEGG enrichment analyses being performed to screen the possible underlying mechanisms. The core targets were then obtained through construction of protein-protein interaction (PPI) network maps using Cytoscape software. ResultsThe network pharmacology analyses showed that 73 common targets for curcumin, photodynamics, and systemic lupus erythematosus. The GO enrichment analysis and KEGG pathway enrichment analysis further highlighted the association between identified targets with 200 biological processes, 25 cellular components, 37 molecular functions and 125 pathways. The core targets including AKT1, ALB, TNF, EGFR, CASP3, HSP90AA1, STAT3, HRAS, SRC, and MMP9 were further predicted through PPI network analysis. ConclusionThis study provided a basis for the in-depth exploration of the mechanism of curcumin photodynamic therapy for systemic lupus erythematosus.

Identification of potential therapeutic targets for systemic lupus erythematosus based on GEO database analysis and Mendelian randomization analysis.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease. Current treatments mainly rely on immunosuppressants, which lack specificity and pose challenges during treatment. This study aims to deeply explore the molecular pathogenic mechanism of SLE through gene expression databases (GEO) and bioinformatics analysis methods, combined with Mendelian randomization analysis, to provide key clues for new therapeutic targets. In this study, the SLE-related gene chip dataset GSE65391 was selected from the GEO database, and the data were preprocessed and statistically analyzed using R language and bioinformatics tools. Differential expression analysis, weighted gene co-expression network analysis (WGCNA), GO, and KEGG enrichment analysis were used to screen differentially expressed genes (DEGs) for functional annotation and pathway localization. Furthermore, Mendelian randomization analysis was conducted to identify core genes closely related to SLE risk, and immune cell infiltration analysis and compound molecular docking studies were performed on the core gene ISG15. The study successfully screened 3,456 DEGs and identified core gene modules highly related to SLE through WGCNA analysis, including key genes closely related to the pathogenesis of SLE, such as STAT1, DDX58, ISG15, IRF7, and IFIH1. In particular, this study found a significant positive correlation between the ISG15 gene and SLE, suggesting that it may be a potential risk factor for SLE. Additionally, through molecular docking technology, it was discovered that the ISG15 gene can effectively bind to two compounds, genistein, and flavopiridol, which have anti-inflammatory and immunosuppressive effects, respectively. This provides new potential drug targets for SLE treatment. As an immunomodulatory cytokine, ISG15 plays a crucial role in the pathogenesis of SLE. This study found that variations in the ISG15 gene may increase the risk of SLE and exacerbate inflammatory responses and tissue damage through multiple mechanisms. Furthermore, molecular docking revealed that genistein and flavopiridol can effectively bind to ISG15, offering a new approach for SLE treatment. These two compounds, with their anti-inflammatory and immunosuppressive properties, have the potential to slow the progression of SLE by influencing the expression and function of ISG15. Through comprehensive bioinformatics analysis and Mendelian randomization analysis, this study deeply explored the molecular pathogenic mechanism of SLE and successfully identified ISG15 as a potential therapeutic target for SLE. Simultaneously, molecular docking technology revealed that two compounds, genistein and flavopiridol, have potential therapeutic effects with ISG15, providing new potential drugs for SLE treatment. These discoveries not only enhance our understanding of the pathogenesis of SLE but also provide important clues for developing new treatment strategies.

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.

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.

Effect of remission, clinical remission with active serology, and glucocorticoid dosage on the pregnancy outcome of pregnant patients with systemic lupus erythematosus

BackgroundRemission is a key treatment target in systemic lupus erythematosus (SLE) management. Given the direct correlation between lupus flares and elevated risks of adverse pregnancy outcomes (APOs), securing remission before conception becomes crucial. However, the association between clinical remission with active serology, and the risk of APOs is not thoroughly understood. Additionally, determining the optimal glucocorticoid dosage during pregnancy to mitigate APO risks remains under-researched. This study investigated the risk of APOs in relation to remission/serological activity status in patients in clinical remission/glucocorticoid dosage.MethodsPregnant patients with SLE, who were followed up at two Japanese tertiary referral centers, and had their remission status assessed at conception, were included in this study. We categorized the patients into two groups based on whether they achieved Zen/Doria remission at conception and analyzed the APO ratio. We also examined the influence of serological activity in pregnant patients with clinical remission and analyzed the optimal glucocorticoid dosage to minimize the APO ratio.ResultsOf the 96 pregnancies included, 59 achieved remission at conception. Pregnant patients who achieved remission showed a significant decrease in the APO ratio compared with those who did not. (overall APO: odds ratio (OR) 0.27, 95% confidence interval (CI) 0.11–0.65, p < 0.01, maternal APO: OR 0.34, 95%CI 0.13–0.85, p = 0.021, neonatal APO: OR 0.39, 95%CI 0.17–0.90, p = 0.028). Conversely, no statistical difference was observed in the APO ratio based on serological activity in pregnant patients with clinical remission. (overall APO: OR 0.62, 95%CI 0.21–1.79, p = 0.37, maternal APO: OR 1.25, 95%CI 0.32–4.85, p = 0.75, neonatal APO: OR 0.83, 95%CI 0.29–2.39, p = 0.73). A glucocorticoid dose of prednisolone equivalent ≥ 7.5 mg/day at conception correlated with increased APO. (overall APO: OR 3.01, 95%CI 1.23–7.39, p = 0.016, neonatal APO: OR 2.98, 95% CI:1.23–7.22, p = 0.016).ConclusionsEven with active serology, achieving clinical remission can be a clinical target for reducing APOs in patients who wish to conceive. In addition, if clinically feasible, reducing the glucocorticoid dosage to < 7.5 mg/day before conception could be another predictive factor.

CADHERIN-11 regulation of myeloid phagocytes and autoimmune inflammation in murine lupus

Background and objectiveUnderstanding the regulation of efferocytosis by myeloid phagocytes is important in identifying novel targets in systemic lupus erythematosus (SLE). Cadherin-11 (CDH11), a cell adhesion molecule, is implicated in inflammatory arthritis and fibrosis and recently been shown to regulate macrophage phagocytosis. The extent and mechanism of this regulation is unknown. Our objective was to examine the extent to which CDH11 regulates myeloid phagocytes and contributes to autoimmunity and tissue inflammation. MethodsWe analyzed efferocytosis in macrophages and dendritic cells (DCs) from WT and Cdh11−/− mice and investigated the mechanisms in vitro. We investigated the role of CDH11 in disease development in vivo using the pristane induced lupus model. To translate the clinical relevance of CDH11 in human disease, we measured serum CDH11 levels in two independent pediatric SLE (pSLE) cohorts and healthy controls. ResultsUsing bone marrow derived macrophages (BMDMs) and DCs (BMDCs), we found impaired efferocytosis in phagocytes from Cdh11−/− mice, mediated by downregulated efferocytosis receptor expression and RhoGTPase activation. Specifically, loss of CDH11 downregulated Mertk expression and Rac1 activation in BMDMs, and integrin αVβ3 expression and Cdc42 activation in BMDCs, highlighting distinct pathways. In vivo, Cdh11−/− mice displayed defective efferocytosis and increased accumulation of apoptotic debris in pristane-induced lupus. Further, Cdh11−/− mice had enhanced systemic inflammation and autoimmune inflammation with increased anti-dsDNA autoantibodies, splenomegaly, type I interferons, and inflammatory cytokines. Paradoxically, at the tissue level, Cdh11−/− mice were protected against glomerulonephritis, indicating a dual role in murine lupus. Finally, SLE patients had increased serum CDH11 compared to controls. ConclusionThis study highlights a novel role of CDH11 in regulating myeloid cells and efferocytosis and its potential as a contributor to development in autoimmunity murine lupus. Despite the increase in autoimmunity, Cdh11−/− mice developed decreased tissue inflammation and damage.

JAK Inhibition as a Potential Treatment Target in Systemic Lupus Erythematosus.

Janus kinase (JAK)/signal transducers and activators of transcription (STATs) are a group of molecules responsible for signal transduction of multiple cytokines and growth factors in different cell types, involved in the maintenance of immune tolerance. Thus, the dysregulation of this pathway plays a crucial role in the pathogenesis of multiple autoimmune, inflammatory, and allergic diseases and is an attractive treatment target. JAK inhibitors (JAKinibs) have been approved in the treatment of multiple autoimmune diseases including rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (SPA). In SLE, there is a plethora of ongoing trials evaluating their efficacy, with tofacitinib, baricitinib and deucravacitinib showing promising results, without major safety concerns. In this review, we will discuss the rationale of targeting JAKinibs in SLE and summarize the clinical data of efficacy and safety of JAKinibs in SLE patients.

Pragmatic targets for moderate/severe SLE and their implications for clinical care and trial design: sustained DORIS or LLDAS for at least 6 months is sufficient while their attainment for at least 24 months ensures high specificity for damage-free progression

ObjectivesTreatment targets in systemic lupus erythematosus (SLE) have been validated in unselected—in terms of severity—cohorts, which limits their generalisability. We assessed remission (Definition of Remission in SLE (DORIS)) and Lupus...

Novel therapeutic targets in systemic lupus erythematosus

Novel therapeutic targets in systemic lupus erythematosus

GDF-15: A Potential Biomarker and Therapeutic Target in Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a rheumatic disease. Growth differentiation factor 15 (GDF-15) is a member of transforming growth factor-β superfamily. To date, association of GDF-15 with SLE pathogenesis is not clarified. This study discussed GDF-15 serum levels and gene polymorphisms in SLE patients and lupus mouse model further demonstrated the role of GDF-15 in lupus development. We conducted two independent case-control studies for SLE patients. One is to evaluate serum levels of GDF-15 in 54 SLE patients and 90 healthy controls, and the other one is to analyze gene polymorphisms of GDF-15 in 289 SLE patients and 525 healthy controls. Serum levels of GDF-15 were detected by ELISA. GDF-15 gene polymorphisms (rs1055150, rs1058587, rs1059519, rs1059369, rs1227731, rs4808793, and rs16982345) were genotyped by the Kompetitive Allele-Specific PCR (KASP) method. Addition of recombinant GDF-15 into pristane-induced lupus mice evaluated histological and serological changes. Results showed that serum levels of GDF-15 were overexpressed in SLE patients and associated with disease activity. Polymorphisms rs1055150, rs1059369, rs1059519, and rs4808793 of GDF-15 gene were related to SLE risk. Lupus mice showed splenomegaly, severe histological scores, and high levels of autoantibodies [antinuclear antibodies (ANA) and total immunoglobulin G (IgG)], whereas administration of GDF-15 into lupus mice reduced the histological changes. Percentages of CD8+, CD11b+, CD19+, CD11C+ cells, TH2 cells, and pro-inflammatory cytokines (IL-1β, IL-2, IL-4, IL-21, and IL-22) were reduced after GDF-15 treatment in lupus mice. In conclusion, GDF-15 was related to lupus pathogenesis and inhibited lupus development.

Identification of Mitofusin 1 and Complement Component 1q Subcomponent Binding Protein as Mitochondrial Targets in Systemic Lupus Erythematosus.

Mitochondria are organelles that exhibit several bacterial features, such as a double-stranded genome with hypomethylated CpG islands, formylated proteins, and cardiolipin-containing membranes. In systemic lupus erythematosus (SLE), mitochondria and their inner components are released into the extracellular space, potentially eliciting a proinflammatory response from the immune system. While cardiolipin and mitochondrial DNA and RNA are confirmed targets of autoantibodies, other antigenic mitochondrial proteins in SLE remain to be identified. The present study was undertaken to characterize the protein repertoire recognized by antimitochondrial antibodies (AMAs) in patients with SLE. Using shotgun proteomic profiling, we identified 1,345 proteins, 431 of which were associated with the mitochondrial proteome. Immunoreactivities to several of these candidate proteins were assessed in serum samples from a local cohort (n = 30 healthy donors and 87 patients with SLE) using enzyme-linked immunosorbent assay, and further analyzed for associations with demographic and disease characteristics. We determined that IgG antibodies to the complement component C1q binding protein were significantly elevated in the patients with SLE (P= 0.049) and were also associated with lupus anticoagulant positivity (P= 0.049). Elevated levels of IgG antibodies against mitochondrial protein mitofusin 1 (MFN-1) were promising predictors of SLE diagnosis in our cohort (adjusted odds ratio 2.99 [95% confidence interval 1.39-6.43], P= 0.0044). Moreover, increased levels of anti-MFN-1 were associated with the presence of antiphospholipids (P= 0.011) and anti-double-stranded DNA (P= 0.0005). In this study, we characterized the mitochondrial repertoire targeted by AMAs in the setting of SLE. Our results indicate that autoantibodies can recognize secreted and/or surface proteins of mitochondrial origin. Profiling of the AMA repertoire in large prospective cohorts may improve our knowledge of mitochondrial biomarkers and their usefulness for patient stratification.

The Potential of Nrf2 Activation as a Therapeutic Target in Systemic Lupus Erythematosus.

Inflammation and oxidative stress are well established in systemic lupus erythematosus (SLE) and are critical to the pathogenesis of autoimmune diseases. The transcription factor NF-E2 related factor 2 (Nrf2) is a central regulator of cellular anti-oxidative responses, inflammation, and restoration of redox balance. Accumulating reports support an emerging role for the regulation of Nrf2 in SLE. These include findings on the development of lupus-like autoimmune nephritis and altered immune cell populations in mice lacking Nrf2, as well as decreased Nrf2 abundance in the dendritic cells of patients with SLE. Nrf2-inducing agents have been shown to alleviate oxidative and inflammatory stress and reduce tissue injury in SLE mouse models. Since Nrf2 expression can be increased in activated T cells, the precise role of Nrf2 activation in different immune cell types and their function remains to be defined. However, targeting Nrf2 for the treatment of diseases associated with oxidative stress and inflammation, such as SLE, is promising. As investigation of Nrf2-inducing agents in clinical trials grows, defining the signaling and molecular mechanisms of action and downstream effects in response to different Nrf2-inducing agents in specific cells, tissues, and diseases, will be critical for effective clinical use.

Meant to B: B cells as a therapeutic target in systemic lupus erythematosus.

B cells have a prominent role in the pathogenesis of systemic lupus erythematosus (SLE). They are mediators of inflammation through the production of pathogenic antibodies that augment inflammation and cause direct tissue and cell damage. Multiple therapeutic agents targeting B cells have been successfully used in mouse models of SLE; however, these preclinical studies have led to approval of only one new agent to treat patients with SLE: belimumab, a monoclonal antibody targeting B cell-activating factor (BAFF). Integrating the experience acquired from previous clinical trials with the knowledge generated by new studies about mechanisms of B cell contributions to SLE in specific groups of patients is critical to the development of new treatment strategies that will help to improve outcomes in patients with SLE. In particular, a sharper focus on B cell differentiation to plasma cells is warranted.

Basophils and IgE contribute to mixed connective tissue disease development

Mixed connective tissue disease (MCTD) is a rare and complex autoimmune disease that presents mixed features with other connective tissue diseases, such as systemic lupus erythematosus, systemic sclerosis, and myositis. It is characterized by high levels of anti-U1 small nuclear ribonucleoprotein 70k autoantibodies and a high incidence of life-threatening pulmonary involvement. The pathophysiology of MCTD is not well understood, and no specific treatment is yet available for the patients. Basophils and IgE play a role in the development of systemic lupus erythematosus and thus represent new therapeutic targets for systemic lupus erythematosus and other diseases involving basophils and IgE in their pathogenesis. We sought to investigate the role of basophils and IgE in the pathophysiology of MCTD. Basophil activation status and the presence of autoreactive IgE were assessed in peripheral blood of a cohort of patients with MCTD and in an MCTD-like mouse model. Basophil depletion and IgE-deficient animals were used to investigate the contribution of basophils and IgE in the lung pathology development of this mouse model. Patients with MCTD have a peripheral basopenia and activated blood basophils overexpressing C-C chemokine receptor 3. Autoreactive IgE raised against the main MCTD autoantigen U1 small nuclear ribonucleoprotein 70k were found in nearly 80% of the patients from the cohort. Basophil activation and IgE anti-U1 small nuclear ribonucleoprotein 70k were also observed in the MCTD-like mouse model along with basophil accumulation in lymph nodes and lungs. Basophil depletion dampened lung pathology, and IgE deficiency prevented its development. Basophils and IgE contribute to MCTD pathophysiology and represent new candidate therapeutic targets for patients with MCTD.

The patient's perspective: are quality of life and disease burden a possible treatment target in systemic lupus erythematosus?

A few decades ago, the therapy goal of patients with systemic lupus erythematosus (SLE) was survival and the prevention of organ failure. Today, clinical remission and low disease activity are believed to be the optimal therapeutic targets. These aims are difficult to reach for many patients, but they still do not address the health-related quality of life (QoL) that is significantly impaired in SLE patients. Even in the state of remission, QoL and fatigue are insufficient controlled. Thus, patient-oriented research is essential to design new strategies for the management of lupus patients. The INTEGRATE project analyses the patients’ and physicians’ perspectives to pave the way to design an innovative therapeutic strategy for lupus and focuses on the multifaceted dimensions of the disease burden. Shared decision making (SDM) could include the patient’s perspective of SLE to treatment strategy and consider QoL and the burden of lupus into the process of therapy decision.

A Critical Role for Mucosal-Associated Invariant T Cells as Regulators and Therapeutic Targets in Systemic Lupus Erythematosus.

Mucosal-associated invariant T (MAIT) cells are a subset of innate-like lymphocytes that are restricted by major histocompatibility complex-related molecule 1 (MR1). In this study, we investigated the role of MAIT cells in the pathogenesis of lupus in FcγRIIb−/−Yaa mice, a spontaneous animal model of lupus. Using two approaches of MAIT cell deficiency, MR1 knockout animals and a newly synthesized inhibitory MR1 ligand, we demonstrate that MAIT cells augment the disease course of lupus by enhancing autoantibody production and tissue inflammation. MR1 deficiency reduced germinal center responses and T cell responses in these mice. Suppression of MAIT cell activation by the inhibitory MR1 ligand reduced autoantibody production and lupus nephritis in FcγRIIb−/−Yaa mice. MAIT cells directly enhanced autoantibody production by B cells in vitro. Our results indicate the contribution of MAIT cells to lupus pathology and the potential of these cells as novel therapeutic targets for autoimmune diseases such as lupus.

Design and validation of an immuno-PCR assay for IFN-α2b quantification in human plasma.

Aim: Nowadays, IFN-α is considered a promising therapeutic target for systemic lupus erythematosus. An immuno-PCR (iPCR) was developed to quantify low amounts of IFN-α in human plasma followed by a deep analysis of the methodologic robustness throughout quality by design approach. Results: An accurate, sensitive, selective and versatile iPCR was validated. The critical iPCR procedural steps were identified, applying a Plackett-Burman design. Also, this assay demonstrated an outstanding LOD of 0.3pg/ml. A significant aspect relies on its high versatility to detect and quantify other cytokines in human plasma as the appropriate biotinylated antibody is employed. Conclusion: This reliable iPCR assay can be clinically used as an alternative method for quantitating and detecting low IFN-α2b concentrations in human plasma samples.

The Progress of Investigating the CD137-CD137L Axis as a Potential Target for Systemic Lupus Erythematosus.

Costimulatory molecules facilitate cross-talks among leukocytes via mutual stimulatory and inhibitory signalling, contributing to diverse immunological outcomes in normal physiological responses and pathological conditions. Systemic lupus erythematosus (SLE) is a complex multi-systemic autoimmune condition in which cellular communication through the involvement of costimulatory molecules is crucial in driving proinflammatory responses from the stage of autoantigen presentation to the subsequent process of pathogenic autoantibody production. While the physiology of the costimulatory systems including OX40-OX40L, CD28/CTLA-4-CD80/86, ICOS-B7RP1 and CD70-CD27 has been relatively well studied in SLE, recent data on the immunopathology of the CD137-CD137 ligand (CD137L) system in murine lupus models and patients with SLE highlight the critical role of this costimulatory system in initiating and perpetuating the diverse clinical and serological phenotypes of SLE. CD137, a membrane-bound receptor which belongs to the tumour necrosis factor receptor superfamily, is mainly expressed on activated T cells. Activation of the CD137 receptor via its interaction with CD137L which is expressed on antigen present cells (APC) including B cells, triggers bi-directional signalling; that is, signalling through CD137 as well as signalling through CD137L (reverse signalling), which further activates T cells and polarizes them to the Th1/Tc1 pathway. Further, via reverse CD137L signalling it enhances differentiation and maturation of the APC, particularly of dendritic cells, which subsequently drive proinflammatory cytokine production. In this review, recent data including our experience in the manipulation of CD137L signalling pertaining to the pathophysiology of SLE will be critically reviewed. More in-depth understanding of the biology of the CD137-CD137L co-stimulation system opens an opportunity to identify new prognostic biomarkers and the design of novel therapeutic approaches for advancing the management of SLE.

Determinants of health-related quality of life in systemic lupus erythematosus: amonocentric, retrospective long-term observational study in Germany

Improvement of health-related quality of life (HRQoL) is aprioritized treatment target in systemic lupus erythematosus (SLE). Aretrospective chart review of patients with repeated HRQoL measurements from the outpatient department was conducted in order to better understand which factors drive HRQoL in established SLE. Of particular interest was the association between HRQoL and disease activity. The medical outcomes study short form36 (SF-36), systemic lupus activity measure (SLAM) and routine clinical data of 169 patients (83% female, mean age 40.3 ± 13years, disease duration 9.4 ± 7years) over an average of 7.1 ± 4.2years were available for analysis by linear mixed modelling. Factors associated with the physical component summary (PCS) and mental component summary (MCS) of the SF-36 were assessed. The proportion of HRQoL which could be explained by the variables was estimated by marginal R2 (mR2) and conditional R2 (cR2). At baseline, SLE patients showed a reduced HRQoL in all subscales of the SF-36 including PCS and MCS with the exception of vitality. A higher PCS over time was significantly associated with concurrent parameters, such as intake of antimalarial drugs, no glucocorticoid use, less fatigue, lower disease activity as well as to the baseline parameters of younger age and higher PCS (mR2 54.7%, cR2 59.9%). A higher MCS was associated with concurrent use of glucocorticoids and a higher baseline MCS (mR2 21.7%, cR2 25.1%). The use of antimalarial drugs and no glucocorticoid intake as well as low current disease activity are modifiable factors associated with a better physical HRQoL. The mental component of HRQoL was poorly represented by conventional parameters and not associated with parameters of disease activity in the present study cohort.

Treat to Target in Systemic Lupus Erythematosus.

The treat-to-target principle of controlling inflammatory disease activity by means of disease-modifying antirheumatic drugs or immunosuppressive drugs also pertains to systemic lupus erythematosus (SLE). However, in SLE, intensifying immunosuppression with higher-dose glucocorticoids may worsen outcomes. Therefore, all current recommendations favor better disease control while limiting daily glucocorticoid doses to a maximum of 5 or 7.5 mg of prednisolone daily. Hydroxychloroquine and other prophylactic measures are added, and antiphospholipid syndrome is treated with anticoagulation and not with immunosuppression, which makes the approach of treat to target slightly more complex, mirroring the complexity of the disease.