Due to its stimulatory potential for immunomodulatory CD4+ regulatory T (Treg) cells, low-dose interleukin-2 (IL-2) immunotherapy has gained considerable attention for the treatment of autoimmune diseases. In this investigator-initiated single-arm non-placebo-controlled phase-2 clinical trial of low-dose IL-2 immunotherapy in systemic lupus erythematosus (SLE) patients, we generated a comprehensive atlas of in vivo human immune responses to low-dose IL-2. We performed an in-depth study of circulating and cutaneous immune cells by imaging mass cytometry, high-parameter flow cytometry, transcriptomics, and targeted serum proteomics. Low-dose IL-2 stimulated various circulating immune cells, including Treg cells with a skin-homing phenotype that appeared in the skin of SLE patients in close interaction with endothelial cells. Analysis of surface proteins and transcriptomes revealed different IL-2-driven Treg cell activation programs, including gut-homing CD38+, skin-homing HLA-DR+, and highly proliferative inflammation-homing CD38+ HLA-DR+ Treg cells. Collectively, these data define the distinct human Treg cell subsets that are responsive to IL-2 immunotherapy.

UNASSIGNED: This study explores the issue of paper-and-pencil screening tests for bipolar disorder, often leading to false positives. It discusses hypotheses that connect MDQ positivity with sleep disorders, a decline in health-related quality of life, and the impact of the COVID-19 pandemic on mood disorders. The study proposes that MDQ identifies a \"Dysregulation of Mood, Energy, and Social Rhythms Syndrome\" (DYMERS), indicating a stress-related condition. It aims to investigate the association between MDQ positivity and systemic lupus erythematosus (SLE) in comparison to other chronic disorders.
UNASSIGNED: This case-control study, conducted from April 2019 to February 2020, investigated MDQ positivity in patients with SLE. Ethical approvals were obtained, and statistical analysis was used for data assessment.
UNASSIGNED: This is a case-controlled study where MDQ positivity was significantly higher in systemic lupus erythematosus cases than controls. The analysis compared gender, age, and the presence of depressive episodes between MDQ-positive and MDQ-negative cases, revealing some differences but no significant variations. Interestingly, no association with high prednisone or biologics use was observed. The frequency of MDQ positivity in systemic lupus erythematosus was compared to other chronic pathologies, revealing varying associations with each condition.
UNASSIGNED: This study reveals a high rate of (MDQ) positivity in systemic lupus erythematosus (SLE), associated with the risk of bipolar disorder in SLE. Notable discrepancies in MDQ positivity risk factors between SLE and bipolar disorder are observed. The study emphasizes the ability of MDQ to identify a distinct syndrome characterized by rhythm dysregulation, posing a risk for bipolar disorder and other disorders.

High mobility group box proterin-1 (HMGB-1) is a multifunctional protein that can be released by various programmed cell deaths (PCDs), such as necroptosis and ferroptosis. PCDs play a critical role in the pathogenesis of systemic lupus erythematosus (SLE). However, the role of HMGB-1 in the process of SLE remains unclear. This study aims to demonstrate the potential diagnosing role of serum HMGB-1 in SLE that released by necroptosis and ferroptosis. We found that the serum levels of HMGB-1, receptor-interacting protein kinase 3 (RIPK3) /mixed lineage kinase domain-like protein (MLKL) related with necroptosis, and metabolites associated with ferroptosis were significantly upregulated in SLE patients compared to HC individuals. These serum levels were positively correlated with SLE disease activity. Additionally, the serum level of HMGB-1 showed a strong positive correlated with the levels of RIPK3/MLKL and ferroptosis metabolites. Moreover, the serum level of HMGB-1 was correlated with renal involvement and high-antinuclear antibodies (ANA) titer. After SLE serum and interferon γ (IFN-γ) treatment in vitro, the level of necroptosis and ferroptosis markers were activated and HMGB1 was released both in HEK293 and HK2 cells. Clinically, HMGB-1 was considered as a significant independent risk factor in SLE serum by binary logistic assay. Notably, HMGB-1 exhibited outstanding diagnostic ability for SLE by the area under the curve (AUC) in receiver operating characteristic (ROC) curve analysis. Taken together, our study indicates that the serum level of HMGB-1 is a promising biomarker for the diagnosis and monitoring of SLE.

Systemic lupus erythematosus (SLE) is a chronic autoimmune condition that can affect multiple organ systems and is heterogenous in its presentation and response to therapy. When diagnosed in childhood, SLE is associated with increased morbidity and mortality compared to adult SLE, often requiring substantial immunosuppression with the risk of significant side effects. There remains a significant unmet need for new therapies that can improve disease control and reduce glucocorticoid and other toxic medication exposure for patients with severe or refractory disease. The pathogenesis of SLE involves B cell dysregulation and autoantibody production, which are a hallmark of the disease. Currently approved B cell directed therapies often result in incomplete B cell depletion and may not target long-lived plasma cells responsible for SLE autoantibodies. It is hypothesized that by persistently eliminating both B cells and plasmablasts, CAR T therapy can halt autoimmunity and prevent organ damage in patient\'s refractory to current B cell-depleting treatments. Herein we summarize the current preclinical and clinical data utilizing CAR T cells for SLE and discuss the future of this treatment modality for lupus.

OBJECTIVE: To improve our understanding of systemic lupus erythematosus (SLE)-macrophage activation syndrome (MAS).
METHODS: A systematic review was performed, to retrieve all those papers on patients with SLE-MAS, in individual or aggregated form. The data in each of these medical records were extracted and analyzed to identify the characteristics of SLE-MAS.
RESULTS: A total of 86 SLE-MAS patients were included (25 males and 61 females. The mean (±standard error of the mean) age was 31.21 ± 1.694 years. MAS occurred as the initial presentation of SLE in 47 people (54.65%) and during the course of SLE in 39 (45.35%). A coinfection was reported in 23 (26.74%) patients. The mean Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score was 16.54 ± 0.9462. Overall, 10 patients (11.63%) died. The SLEDAI-2K score was higher in patients with MAS as an initial manifestation of SLE than in those where MAS occurred during the course of SLE. The proportion of patients receiving steroid pulse therapy was lower in patients with coinfections. The deceased group demonstrated lower platelet and ferritin levels. Multiple regression analysis revealed that age and thrombocytopenia were independent factors associated with poor prognosis. In receiver operating characteristic analysis, a platelet count cutoff value of ≤47 × 109/L was a predictor of poor outcome.
CONCLUSIONS: SLE-MAS patients demonstrated high lupus activity, and lupus activity was especially higher in patients with MAS as an initial manifestation. Lupus activity was the predominant trigger of lupus MAS. Thrombocytopenia was an independent factor for poor prognosis.

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway has been identified as a significant modulator of inflammation in various clinical contexts, including infection, cellular stress, and tissue injury. The extensive participation of the cGAS-STING pathway can be attributed to its ability to detect and control the cellular reaction to DNAs originating from both microorganisms and hosts. These DNAs are well recognized as molecules linked with potential risks. At physiological levels, the STING signaling system exhibits protective effects. However, prolonged stimulation of this pathway contributes to autoimmune disorder pathogenesis. The present paper provides an overview of the activation mechanism of the cGAS-STING signaling pathways and their associated significant functions, as well as therapeutic interventions in the context of systemic lupus erythematosus (SLE). The primary objective is to enhance our comprehension of SLE and facilitate more effective diagnosis and treatment strategies for this condition.

N6-methyladenosine (m6A) modification is the most widespread RNA internal modification involved in RNA metabolism. M6A regulators consist of writers, erasers and readers. They exert their function by methylation, demethylation and recognization respectively, participating in cell biology and immune responses. Previously, the focus of m6A modification is its effect on tumor progress. Currently, extensive m6A-related studies have been performed in autoimmune diseases, such as RA, IBD and SLE, revealing that the unique influence of m6A modification in autoimmunity is undeniable. In this review, we summarize the function of m6A regulators, analyze their roles in pathogenic immune cells, summarize the m6A modification in SLE, and provide the potential m6A-targeting therapies for autoimmune diseases.

BACKGROUND: Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease characterized by immune mechanisms dysregulation, leading to the production of diverse autoantibodies. However, the immune pathways underlying B-cell function and phenotypic abnormalities related to SLE pathogenesis remain incompletely understood.
OBJECTIVE: To explore new markers of SLE activity and potential targets for SLE immunotherapy.
METHODS: Collect peripheral blood mononuclear cells (PBMCs) from SLE patients and healthy controls (HC). Use flow cytometry to detect CD39 and CD73 expression on B cell subsets and enzyme-linked immunosorbent assay (ELISA) to measure adenosine (ADO) concentrations in SLE patients\' serum. Compare CD39+CD73+ B cell subsets frequency and ADO concentrations in SLE patients and HC group. Additionally, analyze the correlation between CD39+CD73+ B cell subsets frequency and clinical laboratory parameters.
RESULTS: CD39 and CD73 are simultaneously highly expressed on CD19+ B cell subsets, with significantly lower frequency of CD39+CD73+ B cell subsets in SLE patients compared to HC group. This frequency negatively correlates with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), C-reactive protein (CRP), and anti-double-stranded DNA (anti-dsDNA) antibodies, while positively correlating with IgM and prothrombin time (PT). Additionally, the frequency of CD39+CD73+ B cell subsets is significantly negatively correlated with IL-6 and IFN-α. In vitro cell experiments demonstrate that adenosine significantly inhibits R848-induced inflammatory cytokine production in a dose-dependent manner.
CONCLUSIONS: The frequency of CD39+CD73+ B cell subsets of SLE patients is decreased, correlating with clinical laboratory parameters and disease activity. Simultaneously, ADO concentration in the patients\' serum is reduced. The CD39+CD73+ B cell/ADO pathway may represent a novel immunotherapy strategy for SLE.

OBJECTIVE: ANA-associated RMDs (ANA-RMDs-SLE, pSS, scleroderma, inflammatory myositis, mixed connective tissue disease (MCTD) and undifferentiated connective tissue disease) are a disease spectrum with overlapping clinical and immunological features. Musculoskeletal inflammation is common and impactful across ANA-RMDs. We evaluated musculoskeletal inflammation (ANA-arthritis) prevalence in a multi-disease ANA-RMD study, assessed its clinical impact across ANA-RMD diagnoses, proposed new basket groupings of patients and evaluated immunological profiles in legacy and new basket contexts.
METHODS: An observational study enrolled ANA-RMD patients. Demographic variables, comorbidities, therapies, disease activity instruments (BILAG, SLEDAI, ESSDAI, physician-VAS), patient-reported outcomes (SF36, FACIT-Fatigue, EQ5D, ICECAP-A, WPAI, patient-VAS) and biomarker profile (6 gene expression scores, flow cytometry, autoantibody profile) were analysed. Reclustering utilized Gaussian Mixture Modelling (GMM). Clinical and immune features of new and legacy clusters were compared.
RESULTS: Inflammatory MSK symptoms were prevalent across ANA-RMDs, in 213/294 patients. In ANA-arthritis patients, most variables did not differ between diagnoses, excluding EQ5D-5L index and mobility domains (lower in MCTD/pSS, both p< 0.05). Fibromyalgia and osteoarthritis prevalence were similar across diagnoses. Therapy use differed significantly, biologic use being greatest in SLE (p< 0.05).GMM yielded two multi-disease clusters; High-MSK disease activity (n = 89) and Low-MSK disease activity (n = 124). High-MSK disease activity contained all patients with active joint swelling and had significantly higher prednisolone usage, PGA and Sm/RNP/SmRNP/Chromatin positivity, Tetherin-MFI and Interferon Score-A activity; with numerically lower fibromyalgia and osteoarthritis prevalence.
CONCLUSIONS: We define ANA-Arthritis, a more clinically and immunologically homogeneous population than existing RMDs for trials, and a more prevalent population for therapies in the clinic.

UNASSIGNED: Systemic Lupus Erythematosus (SLE) is an autoimmune disease with unknown etiology resulting in chronic multi-organ inflammation. Juvenile Systemic Lupus Erythematosus (JSLE) is a specific diagnosis of SLE in juvenile, characterized by oral ulceration.
UNASSIGNED: This case report attempts to provide information for oral medicine specialists in managing JSLE patients with hepatosplenomegaly.
UNASSIGNED: A 17-year-old female patient was referred from the Pediatrics Department with mouth ulcers accompanied by dry lips and a tendency to bleed. The most concerning lesion was located on the left buccal mucosa, a single ulceration measuring 5x6mm. Multiple ulcerations spread over the upper and lower labial mucosa, with haemorrhagic crusts on the lips. Painful ulceration can lead to difficulties in mouth opening and impaired function in eating and drinking. Central erythema was seen on the palate. Pseudomembranous candidiasis was also seen on the patient\'s tongue. The hepatosplenomegaly was confirmed by CT scan, with enzyme values of SGPT (386 U/L) and SGOT (504 U/L).
UNASSIGNED: Administration of 0.9% NaCl was instructed to the patient to maintain oral hygiene and help moisturize lips in order to remove haemorrhagic crusts. Administration of 0.025% hyaluronic acid mouthwash and topical steroid ointment mixture for ulcerated and inflammatory conditions. Drug adjustments were made based on laboratory tests and the patient\'s clinical condition was improving.
UNASSIGNED: Managing oral symptoms helps reduce morbidity in JSLE patients. Topical corticosteroids are considered the first line in controlling oral inflammation. Dentists play a role in improving patients\' oral hygiene with the aim of reducing the risk of other opportunistic infections.