Lupus nephritis (LN), one of the common manifestations of systemic lupus erythematosus, continues to be a principal cause of morbidity and mortality. According to the 2024 Kidney Disease: Improving Global Outcomes guidelines, belimumab has been recommended as adjunct therapy for active LN. However, the differences in its efficacy and safety between refractory and newly diagnosed active LN are unknown. This study aimed to evaluate them in a real-world clinical setting in China.

We enrolled active LN patients who initiated belimumab as adjunct therapy in our centre between June 2021 and January 2024 and divided them into a refractory group and a newly diagnosed group according to previous immunosuppressive therapy. They were followed up for ≥3 months. Renal manifestations, serologic features, Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score and steroids dosage were recorded. We used generalized estimating equations to compare time series data for each group and analyse the change tendency of variables over time. Efficacy endpoints were complete renal response (CRR) and primary efficacy renal response (PERR). Logistic regression models were used to analyse factors associated with renal response.

Of 116 LN patients receiving belimumab in our centre, a total of 89 active LN patients were included in the analysis, with a median treatment duration of 13 months (range 7-22). Among them 47 were in the newly diagnosed group and 42 were in refractory group. At the initiation of belimumab there is no statistical difference in age, gender, SLEDAI-2K score, renal-related markers (proteinuria, serum albumin, estimated glomerular filtration rate and renal histological classification) and serologic features (positive anti-double-stranded DNA, C3, C4) between the two groups. Compared with refractory patients, newly diagnosed patients had significantly shorter LN duration (P < .001) and a larger dosage of steroids (P < .01). During the follow-up period, proteinuria, SLEDAI-2K score and dosage of steroids decreased overall and in each group. The decrease was significantly more pronounced in the newly diagnosed group (P < 0.01, P < 0.001, P < 0.001). For the refractory active LN patients, the estimated probability of CRR and PERR at 12 months was 58.3% and 65.4%, respectively, which was comparable to newly diagnosed patients by logrank test (P = .10, P = .51). No difference was found in adverse event rates (P = .08), time to first renal flare (P = .79) or renal-related events (P = .77). Proteinuria levels at belimumab initiation [odds ratio (OR) 1.306, P = .02] and belimumab treatment duration (OR 0.896, P = .01) were independently associated with renal response.

Compared with refractory LN patients, the add-on treatment with belimumab provides remarkable improvement in newly diagnosed active LN patients, with faster steroids decrease. Our data support the efficacy of early introduction of belimumab in Chinese active LN patients in a real-life setting.

This study evaluated the prevalence and incidence of systemic lupus erythematosus (SLE) in Germany and explored real-world data on sequence of therapy (SOT; sequence of drugs as prescribed in clinical practice).

This retrospective, observational, longitudinal cohort study using German claims data from the WIG2 GmbH Scientific Institute for Health Economics and Health System Research database (January 2011-December 2019), extrapolated to the statutory health insurance (SHI)-insured population, evaluated prevalence and incidence in an epidemiological analysis group and SLE treatment patterns in an incident cohort (subgroup ≥ 18 years of age with incident disease and ≥ 24-month follow-up post index date). Analyses were descriptive.

Based on the epidemiological analysis (N = 3017), annual SLE prevalence per 100,000 gradually increased from 40.47 in 2012 to 59.87 in 2019 in the SHI population. In contrast, annual SLE incidence was relatively stable, ranging from 8.83 in 2012 to 8.86 in 2019. In the incident cohort (n = 941), based on SOT analysis (n = 681), treatment gaps of > 60 days were common: 67.1%, 51.2% and 54.9% in SOT1, SOT2 and SOT3, respectively. Corticosteroids were the most frequent monotherapy in SOT1 (31.0% vs 0% in SOT2/SOT3); 30.0-70.0% of patients received a corticosteroid combination therapy across SOTs. Over 50% of patients in each SOT received an antimalarial therapy (combination or monotherapies). The use of biologic disease-modifying drugs was low, ranging from 0.4% in SOT1 to 9.7% in SOT3.

Our data demonstrate an increased prevalence of SLE with stable incidence in Germany, suggesting improved survival of affected patients. Nevertheless, suboptimal treatment patterns, including limited use of biologics, reflect a high unmet need for optimised and personalised therapies in patients with SLE.

Systemic lupus erythematosus (SLE) is an autoimmune disease that is frequently diagnosed in female patients, caused by multiple interacting factors. It has a complex pathogenesis which can affect almost any organ, from the kidneys to the cardiovascular, pulmonary, neurological, osteoarticular, and hematological systems. The present narrative review seeks to elucidate the role of reactive oxygen species (ROS) in the pathogenesis of SLE. The central question guiding this study is to what extent these serum protein modifications correlate with disease activity and organ damage in SLE. It is characterized by the decreased apoptosis and increased necrosis of T cells and the NETosis of granulocytes. Given the impact of an SLE diagnosis on one's life, this narrative review aims to evaluate the intricacies of oxidative stress and its relevance to the pathogenesis and treatment of the disease. Topics such as understanding processes of oxidative stress, their damaging pathways, oxidative stress biomarkers, and their role in the future assistance of clinical decisions will be discussed in the article. The accurate determination of biomarkers is taught to improve both the diagnosis and the management of the disease, while antioxidant therapy may open a new door for the treatment.

Increasing evidence suggests the beneficial immunomodulatory effects of probiotics can reduce inflammation in systemic lupus erythematosus (SLE). However, there is no summary of the existing evidence available. This study aims to investigate the therapeutic effects of probiotics on SLE in a lupus mouse model by examining various markers, including inflammatory cytokines, Treg cells, disease activity, and gut microbiota. A systematic search was conducted using three databases (Web of Science, PubMed, and Scopus) to identify animal studies that reported the therapeutic benefits of probiotics against SLE. Data extracted from the selected articles were qualitatively synthesized. The SYRCLE risk of bias tool was used to evaluate the risk of bias. Out of a total of 3205 articles, 12 met the inclusion criteria. Probiotic strains, quantities, and routes of administration varied among the studies. The treatment ranged from 8 to 47 weeks. Probiotic strains such as L. fermentum CECT5716, L. casei B255, L. reuteri DSM 17509, L. plantarum LP299v, and L. acidophilus can significantly reduce pro-inflammatory cytokines (TNF-α, IL-12, IL-6, IL-1β, IL-17, and IFN-γ) levels while increasing anti-inflammatory IL-10 and Treg cells. Probiotics also delay the production of autoantibodies, thus prolonging the remission period, decreasing flare frequency, and delaying disease progression. Furthermore, probiotic administration prevents gut dysbiosis, increases intestinal stability, and prevents pathogen colonization. In conclusion, probiotics can be considered a new alternative therapeutic approach for the management of SLE. Further clinical studies are required to investigate and validate the safety and effectiveness of probiotics in humans.

To investigate the dose effect of methylprednisolone (MP) on peripheral lymphocyte profiles in patients with systemic lupus erythematosus (SLE). This study investigated the impact of varied MP doses on peripheral lymphocyte subtypes in SLE patients.

We conducted a prospective study involving 51 SLE patients, categorized into four groups (40 mg/day, 80 mg/day, 500 mg/day, and 1000 mg/day) based on the administered MP dosage during hospitalization. We analyzed the lymphocyte count and proportion in peripheral blood, along with their subpopulations, before and after MP treatment using the paired Mann-Whitney U test.

Treatment with a clinically rational dose of MP (40 mg/day or 80 mg/day) resulted in increased lymphocyte counts, encompassing total lymphocytes, T cells, CD4 + T cells, regulatory T cells (Treg), and effector T cells (Teff) in the short term. Conversely, the counts of these cells decreased with pulse MP (500 mg/day or 1000 mg/day). The percentage of Treg cells and the Treg/Teff ratio increased following 40 mg or 80 mg MP/day treatment, whereas they decreased after pulse therapy. A gradual augmentation in the count and percentage of Treg cells was observed during continuous administration of 40 mg or 80 mg MP/day for 1 week, while in patients receiving pulse therapy, Treg cells tended to decrease during the therapy but rapidly recovered upon MP reduction.

Lower doses of MP in the short term increased Treg cells, inhibiting systemic inflammation in SLE. High-dose pulse therapy exhibited a suppressive effect on Tregs. Key Points • Different dosages of methylprednisolone have variable effects on peripheral lymphocyte subsets. • Methylprednisolone pulse therapy leads to a rapid decrease in Treg cells. • Clinically rational methylprednisolone treatment leads to an increase in Treg cells.

Chronic inflammatory diseases, like Systemic Lupus Erythematosus (SLE), carry an increased risk for atherosclerosis and cardiovascular events, accompanied by impairment of atheroprotective properties of high-density lipoprotein (HDL). In SLE, serum B cell-activating factor (BAFF), a cytokine implicated in disease progression, has been correlated with subclinical atherosclerosis. We investigated the impact of treatment with belimumab -an anti-BAFF monoclonal antibody- on HDL atheroprotective properties and composition in SLE patients.

Serum samples were collected from 35 SLE patients with active disease despite conventional therapy, before and after 6-month add-on treatment with belimumab, and 26 matched healthy individuals. We measured cholesterol efflux and antioxidant capacities, paraoxonase-1 (PON1) activity, serum amyloid A1 (SAA1), myeloperoxidase (MPO) and lipid peroxidation product levels of HDL. LC-MS/MS was performed to analyse the HDL lipidome.

Following treatment with belimumab, cholesterol efflux and antioxidant capacities of HDL were significantly increased in SLE patients and restored to levels of control subjects. HDL-associated PON1 activity was also increased, whereas lipid peroxidation products were decreased following treatment. HDL cholesterol efflux and antioxidant capacities correlated negatively with the disease activity. Changes were noted in the HDL lipidome of SLE patients following belimumab treatment, as well as between SLE patients and healthy individuals, and specific changes in lipid species correlated with functional parameters of HDL.

HDL of SLE patients with active disease displays impaired atheroprotective properties accompanied by distinct lipidomic signatures compared with controls. Belimumab treatment may improve the HDL atheroprotective properties and modify the HDL lipidomic signature in SLE patients, thus potentially mitigating atherosclerosis development.

Traditional initial treatment regimens for lupus nephritis (LN) used oral glucocorticoids (GC) in starting doses up to 1.0 mg/kg/day prednisone equivalent with or without a preceding intravenous methylprednisolone pulse. More recent management guidelines recommend lower starting oral GC doses following intravenous pulse therapy. As there have been no large studies directly comparing patients receiving low versus high initial oral GC doses, this pooled analysis of high-quality randomised controlled trials (RCTs) aims to evaluate differences in efficacy and safety.

Published data were analysed from RCTs that assessed variable GC doses in the standard of care (SOC) treatment arms. Patients receiving starting prednisone doses up to 0.5 mg/kg/day (low dose) were compared with 1.0 mg/kg/day (high dose). Complete renal response requiring urine protein-creatinine ratio <0.5 mg/mg (CRR 0.5), CRR or partial renal response (PRR), serious adverse events (SAE) and SAE due to infections at 12 months of treatment were compared between groups.

417 patients from SOC arms of five studies were exposed to low-dose initial GC after intravenous pulse, while 521 patients from four studies were treated with high-dose oral GC. In patients with low-dose oral GC, 25.2% achieved CRR 0.5 at 12 months compared with 27.2% in high-dose groups, p=0.54. CRR or PRR was attained in 48.7% low-dose vs 43.6% high-dose patients, p=0.14. SAEs and infection SAEs were less common in the low-dose GC group (19.4% vs 31.6%, p<0.001 and 9.8% vs 16.5%, p=0.012, respectively).

Based on pooled RCT data, there was no significant difference in 12-month renal responses between patients receiving low-dose prednisone following intravenous GC compared with those receiving initial high doses. SAEs were less frequent in patients receiving low-dose initial GC. These findings support the use of lower oral GC doses in LN treatment.

Currently, no glucocorticoid dose prediction model is available for clinical practice. This study aimed to utilise machine learning techniques to develop and validate personalised dosage models. Participants were patients with SLE who were registered at Nanfang Hospital and received prednisone. Univariate analysis was used to confirm the feature variables. Subsequently, the random forest (RF) algorithm was utilised to interpolate the absent values of the feature variables. Finally, we assessed the prediction capabilities of 11 machine learning and deep-learning algorithms (Logistic, SVM, RF, Adaboost, Bagging, XGBoost, LightGBM, CatBoost, MLP, and TabNet). Finally, a confusion matrix was used to validate the three regimens. In total, 129 patients met the inclusion criteria. The XGBoost algorithm was selected as the preferred method because of its superior performance, achieving an accuracy of 0.81. The factors exhibiting the highest correlation with the prednisone dose were CYP3A4 (rs4646437), albumin (ALB), haemoglobin (HGB), anti-double-stranded DNA antibodies (Anti-dsDNA), erythrocyte sedimentation rate (ESR), age, and HLA-DQA1 (rs2187668). Based on validation, the precision and recall rates for low-dose prednisone (⩾5 mg but <7.5 mg/d) were 100% and 40% respectively. Similarly, for medium-dose prednisone (⩾7.5 mg but <30 mg/d), the accuracy and recall rates were 88% and 88%, and for high-dose prednisone (⩾30 mg but ⩽100 mg/d), the accuracy and recall rates were 62% and 100% respectively. A robust machine learning model was developed to accurately predict prednisone dosage by integrating the identified genetic and clinical factors.

Systemic Lupus Erythematosus (SLE) is an autoimmune disorder that causes a breakdown of immune tolerance. Current treatments mainly involve general immunosuppression, increasing the risk of infections. On the other hand, Bacillus Calmette-Guérin (BCG) has been investigated as a potential therapy for autoimmune diseases in recent years, prompting an ongoing investigation. This study aimed to evaluate the effect of BCG vaccination on early and late clinical presentation of SLE in a murine disease model. MRL/MPJ-Faslpr mice were immunized with BCG or treated with PBS as a control. The progress of the disease was evaluated at 27 days post-immunization (dpi) (early) and 56 dpi (late). Clinical parameters and proteinuria were monitored. Blood samples were collected for measurement of antinuclear antibodies (ANAs), anti-double-stranded DNA (anti-dsDNA), and cytokine determination was performed using ELISA. Samples collected from mice were analyzed by flow cytometry and histopathology. We observed a clinical improvement in BCG-treated mice, reduced proteinuria in the latter stages of the disease, and decreased TNF-α. However, BCG did not elicit significant changes in ANAs, anti-dsDNA, histopathological scores, or immune cell infiltration. BCG was only partially beneficial in an SLE mouse model, and further research is needed to determine whether the immunity induced by this vaccine can counteract lupus's autoimmune response.

To evaluate the effectiveness and safety of different B cell-targeting biological agents combining with standard of care in patients with lupus nephritis (LN).

Comprehensive literature searches were conducted using PubMed, Embase, Web of Science, and Central in the Cochran Library, spanning from inception to May 20th, 2024. Randomized control trials (RCTs) comparing rituximab (RTX), belimumab, ocrelizumab, obinutuzumab, and anifrolumab in LN were selected. The primary outcomes of interest were related to complete renal remission (CRR), and partial renal remission (PRR). Additionally, we delved into safety outcomes, examining the occurrence of serious adverse events (SAEs), infections, and the discontinuation rates due to adverse events.

A total of 6 RCTs with 1150 patients applying various B cell-targeting biological agents were included. Notably, ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that obinutuzumab (SUCRA 85.2%) has the highest potential superiority in improving CRR, followed by belimumab, ocrelizumab. Regarding the improvement in PRR, obinutuzumab (SUCRA 83.0%) has the highest potential superiority. In terms of safety, with a focus on SAEs, infections, and the discontinuation rates due to adverse events, the results were: SUCRA-based ranking indicated that RTX (SUCRA 74.1%) had the highest probability of postponing SAEs, followed by belimumab and obinutuzumab. Concerning infection reduction, anifrolumab (SUCRA 78.7%) had the highest potential superiority. Safety events monitoring infection occurred better with RTX than with standard therapy (OR = 3.57, 95% CI 1.02, 12.66) and were statistically different. For the discontinuation rates due to adverse events, RTX (SUCRA 88.6%) demonstrated the highest potential superiority.

Concerning the effectiveness and safety outcomes, obinutuzumab, belimumab, and RTX plus standard of care may be superior to the current standard therapy as treatments for LN. This study protocol has been registered with PROSPERO, with a registration number of CRD42024548522.

Systemic 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.

An 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.

An 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.

The 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.

Systemic lupus erythematosus is a chronic autoimmune inflammatory disease characterized by multiple symptoms. The phenolic acids and other flavonoids in Nelumbo nucifera have anti-oxidants, anti-inflammatory, and immunomodulatory activities that are essential for managing SLE through natural sources. This study employs network pharmacology to unveil the multi-target and multi-pathway mechanisms of Nelumbo nucifera as a complementary therapy. The findings are validated through molecular modeling, which includes molecular docking followed by a molecular dynamics study.

Active compounds and targets of SLE were obtained from IMPPAT, KNApAcKFamily and SwissTargetPrediction databases. SLE-related targets were retrieved from GeneCards and OMIM databases. A protein-protein interaction (PPI) network was built to screen out the core targets using Cytoscape software. ShinyGO was used for GO and KEGG pathway enrichment analyses. Interactions between potential targets and active compounds were assessed by molecular docking and molecular dynamics simulation study.

In total, 12 active compounds and 1190 targets of N. nucifera's were identified. A network analysis of the PPI network revealed 10 core targets. GO and KEGG pathway enrichment analyses indicated that the effects of N. nucifera are mediated mainly by AGE-RAGE and other associated signalling pathways. Molecular docking indicated favourable binding affinities, particularly leucocianidol exhibiting less than -4.5 kcal/mol for all 10 targets. Subsequent molecular dynamics simulations of the leucocianidol-ESR1 complex aimed to elucidate the optimal binding complex's stability and flexibility.

Our study unveiled the potential therapeutic mechanism of N. nucifera in managing SLE. These findings provide insights for subsequent experimental validation and open up new avenues for further research in this field.

Patients with systemic lupus erythematosus (SLE) experience greater cardiovascular morbidity and mortality compared to the general population. It is known that endothelial dysfunction, an early indicator of atherosclerosis development, can arise even without the presence of conventional cardiovascular risk factors. In fact, the risk factors contributing to cardiovascular disease can be classified into traditional risk factors and those uniquely associated with SLE such as disease activity, autoantibodies, etc.Furthermore, the pathogenesis of cardiovascular disease in SLE is linked to the activation of both the innate and adaptive immune systems. Given these findings, it is essential for clinicians to acknowledge the heightened CVD risk in SLE patients, perform comprehensive screenings for cardiovascular risk factors, and implement aggressive treatment strategies for those who exhibit signs of clinical CVD. The aim of this review is to summarize the findings on cardiovascular disease in SLE and to examine potential screening and therapeutic strategies for clinical practice.

Systemic lupus erythematosus (SLE) is a multifaceted autoimmune disorder characterized by significant autoantibodies, particularly targeting nuclear antigens. SLE pathogenesis involves genetic, environmental, and hormonal factors. The disease course includes flares and remission and involves various organs. Recent therapeutic progresses, including biologics, have improved management and prognosis, though the long-term impact of novel therapies remains to be determined. Biologics in SLE: Rituximab, the earliest B-cell-oriented biologic, binds CD20 and depletes CD20+ B cells, leading to remission in some SLE patients. Belimumab is a B-cell-activating factor (BAFF) inhibitor with a recent additional indication for lupus nephritis. The CALIBRATE and BLISS-BELIEVE studies investigated combinations of these drugs with conventional therapies, showing varied efficacy. Ocrelizumab and obinutuzumab, newer CD20-oriented SLE therapies, together with ofatumumab and veltuzumab, are also promising. The latest trials highlight their efficacy and safety. Anifrolumab, targeting type-I interferon receptors, was evaluated in the TULIP 1/2 trials. The ongoing TULIP LTE trial supports the long-term safety and efficacy of anifrolumab. Additionally, the IRIS Phase III trial is exploring anifrolumab for lupus nephritis, showing favorable renal responses. Tocilizumab and secukinumab are being assessed for SLE, with mixed outcomes. Several biologics targeting the C5 complement protein, together with immunomodulators and immunotherapeutics, are also under investigation for potential benefits in SLE.

Biologics in SLE target specific immune components, aiming to improve disease control and reduce the side effects of conventional therapy. However, trial outcomes vary due to factors like inclusion criteria and trial design.

Biotechnology progress enables targeted biologic therapies for SLE, reducing disease activity and improving patients' quality of life.

BLyS and APRIL have the capability to bind to B cells within the body, allowing these cells to evade elimination when they should naturally be removed. While BLyS primarily plays a role in B cell development and maturation, APRIL is linked to B cell activation and the secretion of antibodies. Thus, in theory, inhibiting BLyS or APRIL could diminish the population of aberrant B cells that contribute to SLE and reduce disease activity in patients. Telitacicept functions by binding to and neutralizing the activities of both BLyS and APRIL, thus hindering the maturation and survival of plasma cells and fully developed B cells. The design of telitacicept is distinctive; it is not a monoclonal antibody but a TACI-Fc fusion protein generated through recombinant DNA technology. This fusion involves merging gene segments of the TACI protein, which can target BLyS/APRIL simultaneously, with the Fc gene segment of the human IgG protein. The TACI-Fc fusion protein exhibits the combined characteristics of both proteins. Currently utilized for autoimmune disease treatment, telitacicept is undergoing clinical investigations globally to assess its efficacy in managing various autoimmune conditions. This review consolidates information on the mechanistic actions, dosing regimens, pharmacokinetics, efficacy, and safety profile of telitacicept-a dual-targeted biological agent. It integrates findings from prior experiments and pharmacokinetic analyses in the treatment of RA and SLE, striving to offer a comprehensive overview of telitacicept's research advancements.

The objective of this study was to analyze the effect of methylprednisolone pulses (MP), given during the first year after the diagnosis of systemic lupus erythematosus (SLE), in achieving prolonged remission according to the degree of lupus activity at presentation.

We conducted an observational study of routine clinical care data from the Lupus-Cruces-Bordeaux cohort. The end point was prolonged remission (ie, during five consecutive yearly visits). The effect of MP on remission during the first year was analyzed in the whole cohort and according to the baseline Systemic Lupus Erythematosus Disease Activity Index 2000 score: <6, 6 to 12, and >12, reflecting mild, moderate, and severe activity, respectively. For adjustment, logistic regression with propensity score (PS) and other therapeutic covariates was performed.

Two hundred thirty-three patients were included. Prolonged remission was achieved by 132 patients (57%). MP were associated with prolonged remission (PS-adjusted odds ratio [OR] 2.50, 95% confidence interval [CI] 1.04-623, P = 0.042). A strong clinical effect was seen among patients with moderate (adjusted OR 5.28, 95% CI 1.27-21.97, P = 0.022) and moderate-severe SLE activity (adjusted OR 4.07, 95% CI 1.11-14.82, P = 0.033). The administration of MP resulted in reduced average dosages of prednisone during the first year among patient with moderate (mean 6.6 vs 10.2 mg/day, P = 0.017) and severe activity (mean 14 vs 28 mg/day, P = 0.015). The odds of prolonged remission were increased by longer-term use of hydroxychloroquine (HCQ) and decreased by higher initial doses of prednisone.

This study supports the use of MP to induce prolonged remission in patients with SLE, particularly in those with moderate and severe activity. The extended use of HCQ also contributes to achieve prolonged remission.

This study aimed to evaluate the clinical efficacy of belimumab in patients with early systemic lupus erythematosus (SLE), defined as having a disease duration of less than 6 months.

We retrospectively identified patients with SLE in the early stage who received belimumab and standard of care (belimumab group) or standard of care alone (control group) since September 2020. Propensity score matching (PSM) was used to reduce potential bias. The primary endpoint was lupus low disease activity status (LLDAS) at weeks 12 and 24. The secondary endpoints were remission and the proportion of glucocorticoid dose tapering to 7.5 mg/day. The efficacy of belimumab in patients with lupus nephritis was also assessed.

Out of 111 eligible patients, 16 patients in the belimumab group and 31 patients in the control group were identified by 1:2 PSM. At week 24, a significantly higher proportion of individuals achieved low disease activity state (LLDAS) in the belimumab group compared to the control group (56.3% vs. 19.4%, OR = 5.357, 95% CI = 1.417 to 20.260, p = 0.013). Furthermore, more patients in the belimumab group were reduced to low-dose glucocorticoid ( ≤ 7.5 mg/day) at week 24 (75.0% vs. 35.5%, OR = 5.182, 95%CI = 1.339 to 20.058, p = 0.017). Significant improvements in Patient Global Assessment scores were observed at Week 12 and 24 for those treated with belimumab compared to controls. In a subgroup analysis evaluating the efficacy of belimumab in patients with lupus nephritis, 42.9% of the seven individuals treated with belimumab achieved a complete renal response (CRR) by Week 24, and no instances of disease relapse were observed.

In SLE patients with a disease duration of less than 6 months, belimumab treatment can promote LLDAS achievement and reduce glucocorticoid dose, leading to a better prognosis. Introducing belimumab in the early stage of SLE may be a beneficial decision.

Glucocorticoids (GCs) are potent anti-inflammatory and immunosuppressant medications and remain the cornerstone of systemic lupus erythematosus (SLE) therapy. However, ongoing exposure to GCs has the potential to elicit multiple adverse effects. Considering the irreplaceability of GCs in SLE therapy, it is important to explore the optimal regimen of GCs. Here, we compared the long-term efficacy and safety of pulsed and oral GC therapy in a lupus-prone mouse model. Mice were grouped using a randomized block design. We monitored survival rates, proteinuria, serum autoantibodies, and complement 3 (C3) levels up to 28 weeks of age, and assessed renal damage, bone quality, lipid deposition in the liver and marrow, glucose metabolic parameters, and levels of hormones of the hypothalamic-pituitary-adrenal (HPA) axis. Finally, we explored the mechanisms underlying the superior efficacy of the pulse regimen over oral prednisone regimen. We found that both GC regimens alleviated the poor survival rate, proteinuria, and glomerulonephritis, while also reducing serum autoantibodies and increasing the level of C3. The pulsed GC regimen showed less resistance to insulin, less suppression of the HPA axis, less bone loss, and less bone marrow fat deposition than the oral GC regimen. Additionally, GC-induced leucine zipper (GILZ) was significantly overexpressed in the GC pulse group. These results suggest that the GC pulse regimen ameliorated symptoms in lupus-prone mice, with fewer side effects, which may be related to GILZ overexpression. Our findings offer a potentially promising GC treatment option for SLE.

Glucocorticoids (GCs) have revolutionized the management of SLE, providing patients with rapid symptomatic relief and preventing flares when maintained at low dosages. However, there are increasing concerns over GC-associated adverse effects and organ damage, which decrease patients' quality of life (QOL) and increase healthcare costs. This highlights the need to balance effective GC use and minimize toxicity in patients with SLE. Herein, we provide an overview of the theoretical considerations and clinical evidence, in addition to the variations and similarities across nine national and eight international recommendations regarding the use of GCs across SLE manifestations and how these compare with real-world usage. In line with this, we propose possible actions toward the goal of GC Stewardship to improve the QOL for patients with lupus while managing the disease burden.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects multiple organs and systems. It is characterized by the production of abnormal antibodies that attack healthy cells and tissues. The disease presents a wide range of symptoms and severity, from mild to severe. Diagnosis can be complex, but the classification criteria of the American College of Rheumatology (ACR) help to facilitate it. Incidence and prevalence vary considerably worldwide, mainly affecting adult women between the third and fourth decades of life, although it can also occur in childhood. The prognosis of SLE has improved over time, but there is still a risk of irreversible organ damage. Treatment is individualized for each patient and is based on immunosuppression and the use of corticosteroids. Biological therapies, such as monoclonal antibodies, have emerged as a more specific alternative. Methotrexate, antimalarials, glucocorticoids, immunosuppressants, and monoclonal antibodies are some of the medications used to treat SLE. New therapeutic strategies are currently being developed, such as targeted therapies, immunomodulators, and biological agents. Treatment adherence, monitoring, and regular follow-up are important aspects of SLE management. This article aims to describe the characteristics of the new monoclonal antibody therapies that exist for the management of SLE.

Systemic lupus erythematosus (SLE) is a systemic immune disease that classically occurs in young to middle-aged women and may present with cutaneous, renal, haematologic, neurological, and/or other symptoms at the time of diagnosis. Late-onset SLE or SLE in the elderly is a subtype that differs from classic SLE in terms of age group, clinical symptoms, organ involvement and severity.

A 63-year-old female noted to have pancytopenia. The patient was diagnosed with lupus upon obtaining clinical presentations and serological marker, along with high titres of the antinuclear antibody and/or anti-double-stranded DNA antibody. The patient was managed with glucocorticoids and mycophenolate mofetil therapy, which led to a rapid response.

Late-onset SLE accounts for 2-12% of SLE patients with a minimum age of onset of 50 years and older, leading to significant delays in diagnosis. Late-onset SLE differs from early-onset SLE in terms of sex and ethnicity prevalence, clinical symptoms and signs, development of organ damage, disease activity and severity, and prognosis. Some studies have also shown that late-stage SLE patients have higher rates of RF and anti-Ro/anti-La antibody positivity, lower complement titre, and higher incidence of elevated creatinine and decreased creatinine clearance. First-line treatment of pancytopenia is glucocorticoid. In refractory cases, rituximab and immunosuppressants can be used.

It is important to assess any unusual presentation of SLEs when clinical suspicion remains high and conducting further laboratory and imaging investigation.

Symptoms of systemic lupus erythematosus (SLE) vary between patients, but those of increased disease activity typically include musculoskeletal and mucocutaneous manifestations such as joint pain, swelling, and rashes. Several treatment options are available to patients with SLE with variable efficacy. Many treatments, especially corticosteroids, cause unwanted side effects, although little is currently known about patients' preferences for treatments of SLE.

We aimed to identify which attributes of SLE treatment are valued by patients and to quantify their relative importance.

Adult participants with moderate-to-severe SLE were asked to make a series of choices between two hypothetical treatments in an online discrete choice experiment (DCE). A latent class model (LCL) was estimated to analyze choice data. Relative attribute importance (RAI) was calculated to determine the importance of each attribute to participants.

A total of 342 participants from the USA completed the survey. A three-class LCL model was found to have the best fit. Class 1 (non-attenders) had non-significant preferences across all attributes. To achieve a better fit, a constrained LCL (cLCL) model was run with the two remaining classes. The most important attributes for participants in class 2 (benefit-seekers) were joint pain (RAI = 32.0%), non-joint pain (RAI = 21.8%), fatigue (RAI = 20.1%), and skin rashes and itching (RAI = 19.1%). The most important attributes for participants in class 3 (risk-avoiders) were risk of non-severe side effects from corticosteroids (RAI = 28.4%), risk of severe side effects from corticosteroids (RAI = 21.4%), and the risk of infections (RAI = 19.2%). Risk-avoiders were more likely to have been diagnosed with SLE for a longer period (>1 year) and were more likely to have experience with oral corticosteroids.

SLE patients fall into two groups with distinct preferences: benefit-seekers, who prioritize reducing the impact of disease symptoms, and risk-avoiders, who prioritize avoiding treatment risks. The implication of this finding will depend on the reasons for these differences, which warrant further research. Our study suggests that these differences arise due to the impact of disease and treatment experience on preferences. If so, well-informed patients may not be willing to tolerate the risks associated with oral corticosteroids in exchange for their benefits.

Systemic lupus erythematosus (SLE) is associated with a significant risk of atherosclerotic cardiovascular disease, especially in the development of premature atherosclerosis. Specific prediction models for premature atherosclerosis in SLE patients are still limited. The objective of this study was to establish a predictive model for premature atherosclerosis in SLE.

The study collected clinical and laboratory data from 148 SLE patients under the age of 55, between January 2021 and June 2023. The least absolute shrinkage and selection operator logistic regression model was utilized to identify potentially relevant features. Subsequently, a nomogram was developed using multivariable logistic analysis. The performance of the nomogram was evaluated through a receiver-operating characteristic curve, calibration curve, and decision curve analysis (DCA).

A total of 148 SLE patients who fulfilled the inclusion criteria were enrolled in the study, of whom 53 patients (35.81%) met the definition of premature atherosclerosis. Hypertension, antiphospholipid syndrome, azathioprine use, duration of glucocorticoid, and age of patients were included in the multivariable regression. The nomogram, based on the non-overfitting multivariable model, was internally validated and demonstrated sufficient clinical utility for assessing the risk of premature atherosclerosis (area under curve: 0.867).

The comprehensive nomogram constructed in this study serves as a useful and convenient tool for evaluating the risk of premature atherosclerosis in SLE patients. It is helpful for clinicians to early identify SLE patients with premature atherosclerosis and facilitates the implementation of more effective preventive measures. Key Points • SLE patients are at a significantly higher risk of developing premature atherosclerosis compared to the general population, and this risk persists even in cases with low disease activity. Traditional models used to evaluate and predict premature atherosclerosis in SLE patients often underestimate the risk. • This study establishes a comprehensive and visually orientated predictive model of premature atherosclerosis in SLE patients, based on clinical characteristics. • The scoring system allows for convenient and effective prediction of individual incidence of premature atherosclerosis, and could provide valuable information for identification and making further intervention decision.

Autoimmune diseases refer to a group of conditions where the immune system produces an immune response against self-antigens, resulting in tissue damage. These diseases have profound impacts on the health of patients. In recent years, with the rapid development in the field of biomedicine, engineered exosomes have emerged as a noteworthy class of biogenic nanoparticles. By precisely manipulating the cargo and surface markers of exosomes, engineered exosomes have gained enhanced anti-inflammatory, immunomodulatory, and tissue reparative abilities, providing new prospects for the treatment of autoimmune diseases. Engineered exosomes not only facilitate the efficient delivery of bioactive molecules including nucleic acids, proteins, and cytokines, but also possess the capability to modulate immune cell functions, suppress inflammation, and restore immune homeostasis. This review mainly focuses on the applications of engineered exosomes in several typical autoimmune diseases. Additionally, this article comprehensively summarizes the current approaches for modification and engineering of exosomes and outlines their prospects in clinical applications. In conclusion, engineered exosomes, as an innovative therapeutic approach, hold promise for the management of autoimmune diseases. However, while significant progress has been made, further rigorous research is still needed to address the challenges that engineered exosomes may encounter in the therapeutic intervention process, in order to facilitate their successful translation into clinical practice and ultimately benefit a broader population of patients.

Hydroxychloroquine (HCQ) and glucocorticoids (GCs) constitute the oldest and more used drugs in the treatment of systemic lupus erythematosus (SLE). Despite this long experience, both are still subject to a number of uncertainties, mainly regarding the dose.

We review the main mechanisms of action, the clinical and toxic effects of HCQ and GCs and analyze the recommendations for the use of both in guidelines published since 2018. We offer a set of recommendations based on the pharmacology, mechanisms of action and clinical evidence.

HCQ is the backbone therapy for SLE, and a judicious use must be accomplished, using doses that allow a good control of lupus without compromising the safety of treatments very much prolonged over the time. Stable doses of 200 mg/day seem to accomplish both conditions. GCs should be used more judiciously, with methyl-prednisolone pulses as the main therapy for inducing rapid remission and doses ≤5-2.5 mg/day be never exceeded in long-term maintenance treatments.

Systemic lupus erythematosus (SLE) is the most frequent and serious systemic connective tissue disease. Nowadays there is no clear guidance on its treatment in childhood. There are a lot of negative effects of standard-of-care treatment (SOCT), including steroid toxicity. Rituximab (RTX) is the biological B-lymphocyte-depleting agent suggested as a basic therapy in pediatric SLE.

To compare the benefits of RTX above SOCT.

The data from case histories of 79 children from the Saint-Petersburg State Pediatric Medical University from 2012 to 2022 years, were analyzed. The diagnosis of SLE was established with SLICC criteria. We compared the outcomes of treatment of SLE in children treated with and without RTX. Laboratory data, doses of glucocorticosteroids, disease activity measured with SELENA-SLEDAI, and organ damage were assessed at the time of initiation of therapy and one year later.

Patients, treated with RTX initially had a higher degree of disease activity with prevalence of central nervous system and kidney involvement, compared to patients with SOCT. One year later the disease characteristics became similar between groups with a more marked reduction of disease activity (SELENA-SLEDAI activity index) in the children who received RTX [-19 points (17; 23) since baseline] compared to children with SOCT [-10 (5; 15.5) points since baseline, P = 0.001], the number of patients with active lupus nephritis, and daily proteinuria. During RTX therapy, infectious diseases had three patients; one patient developed a bi-cytopenia.

RTX can be considered as the option in the treatment of severe forms of SLE, due to its ability to arrest disease activity compared to SOCT.

Toll-like receptor 7 (TLR7) and TLR8 are single-stranded RNA-sensing endosomal pattern recognition receptors that evolved to defend against viral infections. However, aberrant TLR7/8 activation by endogenous ligands has been implicated in the pathogenesis of autoimmune diseases including systemic lupus erythematosus. TLR activation and type I interferon (IFN) were shown recently to impart resistance to glucocorticoids (GC), which are part of the standard of care for multiple autoimmune diseases. While GCs are effective, a plethora of undesirable effects limit their use. New treatment approaches that allow for the use of lower and safer doses of GCs would be highly beneficial. Herein, we report that a dual TLR7/8 inhibitor (TLR7/8i) increases the effectiveness of GCs in inflammatory settings. Human peripheral blood mononuclear cell studies revealed increased GC sensitivity in the presence of TLR7/8i for reducing inflammatory cytokine production, a synergistic effect that was most pronounced in myeloid cells, particularly monocytes. Gene expression analysis by NanoString and single-cell RNA sequencing revealed that myeloid cells were substantially impacted by combining low-dose TLR7/8i and GC, as evidenced by the effects on nuclear factor-kappa B-regulated cytokines and GC-response genes, although IFNs were affected to a smaller degree. Low dose of TLR7/8i plus GC was more efficacious then either agent alone in the MRL/lpr mouse model of lupus, with improved proteinuria and survival. Overall, our findings indicate a GC-sparing potential for TLR7/8i compounds, suggesting TLR7/8i may offer a new strategy for the treatment of autoimmune diseases. SIGNIFICANCE STATEMENT: Some features of autoimmune diseases may be resistant to glucocorticoids, mediated at least in part by toll-like receptor (TLR) activation, necessitating higher doses that are associated with considerable toxicities. We demonstrate that TLR7/8 inhibition and glucocorticoids work synergistically to reduce inflammation in a cell-type specific manner and suppress disease in a mouse model of lupus. TLR7/8 inhibition is a promising strategy for the treatment of autoimmune diseases and has glucocorticoid-sparing potential.

Autoimmune diseases encompass a broad spectrum of disorders characterized by disturbed immunoregulation leading to the development of specific autoantibodies, resulting in inflammation and multiple organ involvement. A distinction should be made between connective tissue diseases (mainly systemic lupus erythematosus, systemic scleroderma, inflammatory muscle diseases, and rheumatoid arthritis) and vasculitides (mainly small-vessel vasculitis such as antineutrophil cytoplasmic antibody-associated vasculitis and immune-complex mediated vasculitis). Admission of patients with autoimmune diseases to the intensive care unit (ICU) is often triggered by disease flare-ups, infections, and organ failure and is associated with high mortality rates. Management of these patients is complex, including prompt disease identification, immunosuppressive treatment initiation, and life-sustaining therapies, and requires multi-disciplinary involvement. Data about autoimmune diseases in the ICU are limited and there is a need for multicenter, international collaboration to improve patients' diagnosis, management, and outcomes. The objective of this narrative review is to summarize the epidemiology, clinical features, and selected management of severe systemic autoimmune diseases.

The introduction of targeted biological agents in systemic lupus erythematosus (SLE) has created a momentum for improving overall disease management and patients' prognosis. To achieve this, a comprehensive strategy is required spanning the entire patient journey from diagnosis to prevention and management of late complications and comorbidities. In this review, we focus on four aspects that are closely linked to SLE prognosis, namely early disease recognition and treatment initiation, reduction of the cumulative glucocorticoid exposure, attainment of well-defined targets of remission and low disease activity, prevention of flares and, kidney-protective strategies with non-immune-directed agents. We review the recent literature related to these topics in conjunction with the existing treatment recommendations, highlighting areas of uncertainty and providing guidance towards facilitating the care of SLE patients.

Glucocorticoids (GCs) continue to be essential agents for the management of systemic lupus erythematosus, since there are no other drugs able to active remission of active disease so rapidly. However, their potential for causing irreversible damage greatly limit their use. Fortunately, some strategies may help take advantage of their huge anti-inflammatory power while limiting GC-induced side effects. This article reviews the pharmacological basis of GC action and their translation into the clinical ground. We also offer the practical approach for the use of GC in induction and maintenance therapy as well as the strategies for GC withdrawal of the respective practice of the authors. The three main basic principles are a) using methyl-prednisolone pulses to induce remission not only in severe disease; b) limiting initial doses of prednisone to ≤30 mg/d, with rapid tapering to ≤5 mg/d, which should be the dose for maintenance therapy; and c) individualizing the decision and the strategy to withdraw GCs. Long-term therapy with HCQ and the early introduction of immunosuppressive treatment would help achieve these objectives.

V-domain immunoglobulin suppressor of T-cell activation (VISTA), an important negative checkpoint protein, participates in immunoregulation. Systemic lupus erythematosus (SLE) is an autoimmune disease in which patients exhibit high levels of autoantibodies and multi-organ tissue injury, primarily involving the kidney and skin. In wild-type (WT) mice and Vsir-/- mice with pristane-induced lupus-like disease, we found that VISTA deficiency exacerbated the lupus-like disease in mice, possibly through aberrant activation of type I interferon (IFN-I) signaling, CD4+ T cell, and noncanonical nuclear factor-κB (NF-κB) pathway. Surface plasmon resonance results showed that imatinib, an FDA-approved tyrosine kinase inhibitor, may have a high affinity for human VISTA-ECD with a KD value of 0.2009 μM. The biological activities of imatinib and VISTA agonist M351-0056 were studied in monocytes and T cells and in lupus-like disease murine model of chronic graft-versus-host disease (cGVHD) and lupus-prone MRL/lpr mice. VISTA small-molecule agonist reduced the cytokine production of peripheral blood mononuclear cells (PBMCs) and Jurkat cells and inhibited PBMCs proliferation. Moreover, they attenuated the levels of autoantibodies, renal injury, inflammatory cytokines, chemokines, and immune cell expansion in the cGVHD mouse model and MRL/lpr mice. Our findings also demonstrated that VISTA small-molecule agonist ameliorated the development of SLE through improving aberrantly activated IFN-I signaling and noncanonical NF-κB pathway. In conclusion, VISTA has a protective effect on the development and progression of SLE. VISTA agonist M351-0056 and imatinib have been firstly demonstrated to attenuate SLE, suggesting interventions to enhance VISTA function may be effective in treating SLE. VISTA deficiency exacerbates pristane-induced lupus-like disease in mice by promoting activation of the IFN-I and noncanonical NF-κB pathway. Imatinib was screened as a small-molecule VISTA agonist by molecular docking, SPR, and cellular level experiments. VISTA agonists (M351-0056 and imatinib) alleviated lupus-like disease progression in the cGVHD mouse model and MRL/lpr mice by inhibiting activation of IFN-I and noncanonical NF-κB pathway.

Systemic lupus erythematosus (SLE) is a systemic autoimmune inflammatory disease of unknown cause, with heterogeneity in its clinical presentation, as well as variability in its clinical course and prognosis. The current goal of treatment is to achieve disease remission or a state of low activity, and thereby improve the patient's quality of life. Biological therapy in lupus, unlike other entities, although it has not been fully established, in recent years it has burst onto the scene with important therapeutic novelties. This review aims to update the therapeutic tools for the treatment of SLE focusing on the new molecules that have achieved the objectives of their clinical trials.

Systemic lupus erythematosus (SLE) patients are at increased risk of cardiovascular disease (CVD) compared to the general population, despite most patients being young females, who are not classically considered to be at high risk for cardiovascular disease using traditional risk assessment tools. The purpose of this review is to discuss the pathophysiology of atherosclerosis in SLE and raise awareness of the relationship between SLE and CVD.

The increased risk of CVD in SLE patients is multifactorial, due to proatherogenic lipid profiles, immune dysregulation and inflammation, side effects of lupus treatment, and microvascular dysfunction. Conventional CV risk models often underperform in the identification of SLE patients at high risk of atherosclerosis. The use of non-invasive imaging serves as a strategy to identify patients with evidence of subclinical CVD and in the evaluation of symptomatic patients. Identification of subclinical atherosclerosis allows for aggressive management of CV risk factors. SLE patients experience an increased risk of atherosclerotic CVD, which is not solely explained by traditional CV risk factors. It is imperative that clinicians are aware of this association to implement prompt detection and treatment of atherosclerotic CVD in SLE patients.

Lupus nephritis (LN) is a serious manifestation of systemic lupus erythematosus that can lead to end-stage renal disease. Many clinical and prognostic data on which our therapeutic decisions are based come from international cohorts, which have important ethnic and prognostic differences. To identify clinical and prognostic data from patients with LN in Spain, we undertook a bibliographic search of NL-related papers by Spanish authors and published in national and international journals between 2005 and 2022. According to the selected references, renal biopsy is not only essential for LN diagnosis but its repetition can be useful for the follow-up. Regarding LN treatment, standard strategy consists of an induction phase and a maintenance phase. However, as new drugs have been released, a new paradigm of treatment in a single, continuing and personalized phase has been proposed.

Discuss the prognostic significance of kidney flares in patients with lupus nephritis, associated risk factors, and possible preventative strategies.

Recently performed clinical trials and observational cohort studies underscore the high frequency of relapses of kidney disease, following initial response, in patients with proliferative and/or membranous lupus nephritis. Analysis of hard disease outcomes such as progression to chronic kidney disease or end-stage kidney disease, coupled with histological findings from repeat kidney biopsy studies, have drawn attention to the importance of renal function preservation that should be pursued as early as lupus nephritis is diagnosed. In this respect, non-randomized and randomized evidence have suggested a number of factors associated with reduced risk of renal flares such as attaining a very low level of proteinuria (< 700-800 mg/24 h by 12 months), using mycophenolate over azathioprine, adding belimumab to standard therapy, maintaining immunosuppressive/biological treatment for at least 3 to 5 years, and using hydroxychloroquine. Other factors that warrant further clarification include serological activity and the use of repeat kidney biopsy to guide the intensity and duration of treatment in selected cases. The results from ongoing innovative studies integrating kidney histological and clinical outcomes, together with an expanding spectrum of therapies in lupus nephritis, are expected to facilitate individual medical care and long-term disease and patient prognosis.

The oral mucosa can be involved in a wide variety of mucocutaneous conditions that may present primarily in the mouth or affect other cutaneous or mucosal sites. Many of these conditions are immune mediated and typically present as inflammatory mucosal pathology. Patients experiencing such conditions usually seek medical evaluation and treatment due to the associated pain and discomfort and occasionally taste disturbance or dysphagia and the overall deterioration in the oral health-related quality of life. These conditions share some common features and there could be some overlapping in their clinical presentation, which can lead to delays in diagnosis and proper management of patients. Clinicians dealing with such disorders, including dermatologists, need to be aware of the oral manifestations of mucocutaneous conditions, their clinical features, underlying mechanisms, diagnostic approaches, and treatment options, as well as the recent advances in the research on these conditions. This review provides a comprehensive, evidence-based reference for clinicians, with updated insights into a group of immune mediated conditions known to cause oral mucosal pathology. Part one will cover oral lichen planus, erythema multiforme and systemic lupus erythematosus, while part two will cover pemphigus vulgaris and mucous membrane pemphigoid, recurrent aphthous stomatitis, in addition to the less common disorders linear IgA disease, dermatitis herpetiformis and epidermolysis bullosa.

In autoimmune rheumatic diseases, immune hyperactivity and chronic inflammation associate with immune dysregulation and the breakdown of immune self-tolerance. A continued, unresolved imbalance between effector and regulatory immune responses further exacerbates inflammation that ultimately causes tissue and organ damage. Many treatment modalities have been developed to restore the immune tolerance and immmunoregulatory balance in autoimmune rheumatic diseases, including the use of peptide-based therapeutics or the use of nanoparticles-based nanotechnology. This review summarizes the state-of-the-art therapeutic use of peptide-based therapies in autoimmune rheumatic diseases, with a specific focus on lupus.

We aim to clarify the efficacy and safety of switching immunosuppressive drugs and to identify the predictive factors for treatment failure after switching in patients with systemic lupus erythematosus (SLE).

We retrospectively evaluated patients with SLE who switched immunosuppressive drugs for any reason in our hospital between 2015 and 2020. The efficacy endpoints were the change in SLE Disease Activity Index 2000 score, prednisolone dose, and disease status over 12 months, as well as treatment continuation rates. The safety endpoint was the frequency of adverse events over 1 year before and after switching. Cox hazard regression analyses were used to identify the predictive factors for treatment failure.

Thirty-nine patients (age, 41.5 ± 12.6 years; 35 women and 4 men) were analysed. The SLE Disease Activity Index score and prednisolone dose were significantly reduced after switching, with few disease exacerbations over 12 months. The 1- and 2-year continuation rates were 71.4% and 62.3%, respectively. The frequency of adverse events was similar in the year before and after switching the drug. Drug switching due to inadequate efficacy was a predictive factor of less likely treatment failure.

Immunosuppressive drug switching led to reduced disease activity and decreased glucocorticoid dose without disease exacerbations and severe adverse events.

Childhood-onset systemic lupus erythematosus (cSLE) is an autoimmune disease that results in significant damage and often needs more aggressive treatment. Compared to adult-onset SLE, cSLE has a stronger genetic background and more prevalent elevated type I Interferon expression. The management of cSLE is more challenging because the disease itself and treatment can affect physical, psychological and emotional growth and development. High dose oral glucocorticoid (GC) has become the rule for treating moderate to severe cSLE activity. However, GC-related side effects and potential toxicities are problems that cannot be ignored. Recent studies have suggested that GC pulse therapy can achieve disease remission rapidly and reduce GC-related side effects with a reduction in oral prednisone doses. This article reviews characteristics, including pathogenesis and manifestations of cSLE, and summarized the existing evidence on GC therapy, especially on GC pulse therapy in cSLE, followed by our proposal for GC therapy according to the clinical effects and pathogenesis.