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The purpose was to identify shared immune cells and co-disease genes in chronic heart failure (HF) and systemic lupus erythematosus (SLE), as well as explore the potential mechanisms of action between HF and SLE. A collection of peripheral blood mononuclear cells (PBMCs) from ten patients with HF and SLE and ten normal controls (NC) was used for transcriptome sequencing. Differentially expressed genes (DEGs) analysis, enrichment analysis, immune infiltration analysis, weighted gene co-expression network analysis (WGCNA), protein-protein interaction (PPI) analysis, and machine learning were applied for the screening of shared immune cells and co-disease genes in HF and SLE. Gene expression analysis and correlation analysis were used to explore the potential mechanisms of co-disease genes and immune cells in HF and SLE. In this study, it was found that two immune cells, T cells CD4 naïve and Monocytes, displayed similar expression patterns in HF and SLE at the same time. By taking intersection of the above immune cell-associated genes with the DEGs common to both HF and SLE, four immune-associated co-disease genes, CCR7, RNASE2, RNASE3 and CXCL10, were finally identified. CCR7, as one of the four key genes, was significantly down-regulated in HF and SLE, while the rest three key genes were all significantly up-regulated in both diseases. T cells CD4 naïve and Monocytes were first revealed as possible shared immune cells of HF and SLE, and CCR7, RNASE2, RNASE3 and CXCL10 were identified as possible key genes common to HF and SLE as well as potential biomarkers or therapeutic targets for HF and SLE.

It is, so to say, not a prerogative authority assigned to SLE classification criteria that allow them to declare something definitively important about SLE. This is particularly true as criteria-based classification processes overrule the highly needed evolution of concise diagnostic criteria. It is classification criteria that allocate SLE patients into cohorts intended to describe the nature of their disease. Therefore, all major SLE classification criteria since the 1971 preliminary criteria usurp the role of diagnostic criteria. Today´s practice silently accept that the SLE classification process “diagnose” SLE patients despite the fact that classification criteria are not accepted as diagnostic criteria! This is a central paradox in contemporary SLE research strategies. Contemporary SLE cohorts are designed to investigate SLE´s etiological features. However, each cohort that is categorized by classification criteria has one central inherent problem. From theoretical and practical arguments, they embody multiple distinct clinical phenotypes. This raises the critical and principal question if phenotypically heterogenic SLE cohorts are useful to identify basic SLE-specific etiology(ies) and disease process(es). In times to come, we must prioritize development of firm diagnostic criteria for SLE, as the classification criteria have not contributed to reduce the enigmatic character of the syndrome. No radical improvements are visible in the horizon that may lead to concise investigations of SLE in well-defined homogenous SLE cohorts. We must develop new strategies where studies of phenotypically standardized cohorts of SLE must be central elements. Problems related to contemporary SLE classification criteria are contemplated, analyzed, and critically discussed in this study.

Background. Vasculitides represent a heterogeneous group of systemic inflammatory diseases, often difficult to classify and requiring multidisciplinary management.   Case Report. We present the case of a 68-year-old woman with a thoracic aortic aneurysm and a history of recurrent episodes of pneumonia with pleuritis. Since March 2024, she reported worsening pruritus (with a history of contact dermatitis) and alopecia. Starting in October, low-grade fever (T max 38°C), exertional dyspnea, and weight loss appeared. Chest CT scan showed bronchiolar wall thickening with fibrotic-disventilatory strands and an aortic aneurysm (53–55 mm). Admitted to cardiac surgery, on 14/03/2025, she underwent replacement of the ascending aorta with a Dacron valved conduit and aortic valve repair/plasty. Histological examination documented a marked lymphomonocytic infiltrate with tertiary germinal centers in the intima, involvement of the vasa vasorum, mucinoid degeneration, neoangiogenesis of the tunica media, and adventitial thickening with hyalinosis, consistent with giant cell aortitis , even in the absence of granulomas and macrophages and skip lesions. From May 5 to 23, she was admitted to our Rheumatology department for diagnostic work-up. Color Doppler ultrasound of the carotid and vertebral arteries, temporal arteries, renal arteries, and aortic axis was normal. FDG-PET scan showed vascular uptake solely in the ascending aorta, and multiple pulmonary accumulations (right lower lobe, parascissural regions, apices, hilar/paratracheal lymph nodes). HRCT revealed vague peribronchial consolidations suggestive of inflammation. Serology was negative for active infections (Quantiferon, EBV, CMV, HIV, Toxoplasma, Treponema pallidum); ANCA, ENA, RF, IgG4, anti-DNA, and liver autoantibodies were negative. ACPA was weakly positive; Lupus Anticoagulant (LAC) and IgG anticardiolipin antibodies were positive, leading to the initiation of anticoagulation therapy with warfarin (INR target 2.5). ESR 62 mm/h, CRP 9 mg/dL, eosinophils 780 mm³. Blood cultures were negative. Starting on May 13, therapy was initiated with prednisone 25 mg daily at a reduced dosage due to suspected infection, and a reduction in inflammation was observed (ESR 44 mm, CRP 0.09 mg/dL). BAL (bronchoalveolar lavage) for atypical mycobacteria investigation was proposed and is ongoing. A diagnosis of giant cell aortitis with pulmonary involvement (micronodules and tree-in-bud pattern) was made. Excluded diagnosis: Syphilis (negative serology and histology), tuberculous vasculitis (absence of granulomas, dissemination, reactive lymph nodes on PET, CT, and lymph node ultrasound, negative Quantiferon), EGPA (absence of asthma/rhinitis, fixed pulmonary infiltrates, negative ANCA), SLE (initially suspected due to alopecia, dermatitis, and ANA+, but excluded by a dermatologist who diagnosed eczematous atopic dermatitis and alopecia areata).

Background and Objective. To describe our experience with the use of anifrolumab (AFM) in a small single-center cohort of patients (pts) with systemic lupus erythematosus (SLE), with particular focus on the management of refractory manifestations. SLE is a systemic autoimmune disease that can affect virtually any organ or system. Refractory manifestations represent an unmet need in disease management, as they are associated with higher glucocorticoid (GC) exposure, increased risk of cumulative organ damage, and reduced quality of life (QoL). Type I interferons (IFN-I) play a key role in antiviral defense; however, in SLE patients, IFN-I signaling pathways are upregulated both in genetic predisposition and in epigenetic changes characteristic of the disease, contributing to disease onset and activity. Several clinical and laboratory features of SLE—including lymphopenia—are associated with the overexpression of IFN-I–regulated genes, providing a strong rationale for targeting this pathway. Anifrolumab, a monoclonal antibody that inhibits the type I interferon receptor, offers new therapeutic perspectives in this setting.   Materials and Methods. We report on 5 female SLE patients aged 35–64 years, followed from September 2024 to the present. Four pts presented with cutaneous involvement: acute cutaneous lupus (n=2), subacute cutaneous lupus (SCLE)(n=1), and discoid lupus with scarring alopecia (DLE) (n=1). One pt exhibited predominant constitutional (persistent remittent fever up to 39.5°C for ~1 year, fatigue) and hematologic involvement (leukopenia–lymphopenia). These manifestations prompted initiation of AFM therapy. Previous manifestations (currently in remission) included articular (3 pts), serosal (pleural effusion, 1 pt), and renal involvement (class III glomerulonephritis, 1 pt). At the time of our observation, pts (previously followed in other Centers) were receiving hydroxychloroquine (except the pt with constitutional/hematologic involvement, due to intolerance) and GCs (except the pt with DLE, who had discontinued GCs due to lack of efficacy on cutaneous disease). Three of the five pts had a remote history of traditional immunosuppressant use. Anti-dsDNA antibodies were present in 3 pts, and C4 was reduced in 4 pts.   Results. Treatment with AFM led to improvement in all cutaneous manifestations, with complete remission in two cases, after only a few months of therapy. A marked clinical benefit was also observed in the DLE case, a notoriously refractory manifestation (CLASI score improved from 17 [T0] to 8 [T5]). The pt with persistent fever and leukopenia–lymphopenia—also typically refractory—experienced rapid resolution of symptoms and improvement in fatigue (SLEDAI decreased from 6 [T0] to 2 [T2]). All pts were able to taper GCs, with complete withdrawal achieved in two pts with cutaneous disease.   Conclusions. Our findings confirm the efficacy of AFM, as previously demonstrated in clinical trials, across selected SLE disease domains. They highlight the potential to extend precision medicine principles to SLE management and to consider AFM as a valuable therapeutic option for difficult-to-treat manifestations.  

Systemic lupus erythematosus (SLE), often considered the prototype of autoimmune diseases, is characterized by over-activation of the autoimmune system with abnormal functions of innate and adaptive immune cells and the production of a large number of autoantibodies against nuclear components. Given the highly complex and heterogeneous nature of SLE, the pathogenesis of this disease remains incompletely understood and is presumed to involve both genetic and environmental factors. Currently, disturbance of the gut microbiota has emerged as a novel player involved in the pathogenesis of SLE. With in-depth research, the understanding of the intestinal bacteria-host interaction in SLE is much more comprehensive. Recent years have also seen an increase in metabolomics studies in SLE with the attempt to identify potential biomarkers for diagnosis or disease activity monitoring. An intricate relationship between gut microbiome changes and metabolic alterations could help explain the mechanisms by which gut bacteria play roles in the pathogenesis of SLE. Here, we review the role of microbiota dysbiosis in the aetiology of SLE and how intestinal microbiota interact with the host metabolism axis. A proposed treatment strategy for SLE based on gut microbiome (GM) regulation is also discussed in this review. Increasing our understanding of gut microbiota and their function in lupus will provide us with novel opportunities to develop effective and precise diagnostic strategies and to explore potential microbiota-based treatments for patients with lupus.

IntroductionSLE disease activity score (SLE-DAS) is a novel, rapid, continuous and comprehensive score that overcomes the drawbacks of SLEDAI-2 K. Low lupus disease activity state (LLDAS) has been targeted as an endpoint in many clinical trials and as a favourable outcome in clinical practice. Therefore, our objective in the current study is to evaluate the validity of SLE-DAS for defining LLDAS as an objective in the treat-to-target strategy.MethodsA cross-sectional study was carried out on 117 SLE patients who were diagnosed according to Systemic Lupus International Collaborating Clinics (SLICC) classification criteria for SLE. Patients were evaluated for disease activity by both SLEDAI-2 K and SLE-DAS. Additionally, patients were divided according to the SLEDAI-2 K-derived LLDAS definition into two groups: low disease activity (LDA) group and high disease activity (HDA) group. The validity of SLE-DAS for the definition of LLDAS was evaluated in comparison to SLEDAI-2 K.ResultsSLE-DAS shows highly significant positive correlation (r = 0.743, p < 0.001) with SLEDAI-2 K. The ROC curve revealed that SLE-DAS is valid for the assessment of activity with the best detection of LLDAS was at 6.62 with 95.5% sensitivity, 79.3% specificity and 89.6% accuracy. Moreover, it had a good agreement with the SLEDAI-2 K-derived definition of LLDAS (k = 0.765, p < 0.001).ConclusionSLE-DAS is a valid score for the definition of LLDAS which can be used in the clinical practice as a simple and precise standalone criterion.Key Points• Correlation between SLEDAI-2K and SLE-DAS revealed a high significance.• Identify SLE-DAS cut-off 6.62 for the definition of LLDAS.• There is a good agreement between SLEDAI-2K-derived definition of LLDAS and SLE-DAS definition.

Systemic lupus erythematosus is a rare lifelong multi-systemic autoimmune condition. Juvenile-onset SLE (JSLE) is recognized to have a more active disease course when compared with adult-onset disease and patients have a worse long-term survival. Kidney involvement occurs in over 50% of children and treatment decisions are guided by the histological classification. Several international groups have produced treatment protocols that rely on an intense period of immunosuppression to halt the acute kidney inflammatory process, followed by maintenance therapy with close observation for disease improvement and prompt evaluation of disease flares. A reduced glomerular filtration rate at presentation is predictive of later stage chronic kidney disease (CKD) in multivariate analysis. Kidney remission remains suboptimal with only 40–60% of patients achieving complete remission. Kidney flares are seen in over a third of patients. The rate of CKD 5 is reported to be up to 15% and the presence of lupus nephritis (LN) has an established link with an associated increase in mortality. In established kidney failure, transplantation seems to be the optimal kidney replacement modality for this group of patients, ideally after a period of disease quiescence. Modified outcome measures in clinical trials have demonstrated that biologic agents can be effective in this disease. Current biologic agents under investigation include obinutuzimab, belimumab, atacicept, anifrolumab, tocilizumab, eculizumab, dapirolizumab, and abatacept. Future research should focus on discovering early disease biomarkers, including surrogates for later cardiovascular disease, and evaluating biological agents as adjuncts to improve the rates of complete remission and subsequently influence the kidney outcome. The aim of this review article is to summarize the current kidney outcomes for this disease with a view to identifying key areas that may help to reduce the risk of long-term CKD.

Objective To evaluate the prediction and effect of fibrinogen‐to‐albumin ratio (FAR) on active, severe active, and poor prognosis of systemic lupus erythematosus (SLE). Methods One hundred and sixty‐eight patients with SLE who were treated in our hospital were enrolled, the clinical data, laboratory indexes, and disease prognosis of all patients were collected and analyzed. Results Triglyceride (TG), FAR, ESR, and anti‐dsDNA (+) were the influencing factors, while complement 3 (C3) was the protective factor of active SLE, the odds ratio (OR) values were 2.968, 3.698, 2.114, 2.727, and 0.652, respectively (p < 0.05). FAR, ESR, and anti‐dsDNA (+) were the influencing factors, while C3 was the protective factor of severe active SLE, the OR values were 3.791, 1.953, 2.187, and 0.742, respectively (p < 0.05). SLE disease activity index (SLEDAI), TG, FAR, and anti‐dsDNA (+) were the influencing factors, while C3 was the protective factor of poor prognosis SLE, the OR values were 3.024, 2.293, 3.012, 2.323, and 0.801, respectively (p < 0.05). FAR and FIB were positively correlated with SLEDAI, while ALB was negatively correlated with SLEDAI, the related coefficient (r) were 0.398, 0.267, −0.270, respectively. The receiver operating curve (ROC) analysis showed that the predictive values of FAR for active, severe active and poor prognosis SLE were 0.769, 0.769, and 0.734, respectively, were significant higher than FIB and ALB (p < 0.05). Conclusion Fibrinogen‐to‐albumin ratio was an influencing factor of active, severe active, and poor prognosis SLE had higher predictive value than FIB and ALB for the activity and prognosis of SLE. As a new inflammatory marker fibrinogen‐to‐albumin ratio (FAR) has been proved to have good predictive value in the diagnosis and prognosis of diabetes nephropathy, acute renal injury, rheumatoid disease, and so on. However, there is few relevant research on whether it can predict the activity and prognosis of SLE and whether the predictive value is higher than FIB and ALB. Our study compared the predictive value of FIB, ALB, FAR, and analyzed the influencing factors of active, severe active, and poor prognosis SLE, in order to provide a new predictive biomarker for the disease activity and prognosis. Our findings demonstrated that FAR had higher predictive value than FIB and ALB, and high FAR showed great associated with an increasing probability of active, severe active, and poor prognosis SLE, in other words, FAR would be a better potential marker for predicting the severity and prognosis of SLE than the single indicators of FIB and ALB. Please review the article.

BackgroundWe and others have previously shown that IL-2 is essential for TGF-β to allow conversion of naïve CD4+CD25- T cells into CD4+CD25+Foxp3+ Tregs. To further those studies, we recently used IL-2- loaded nanoparticles (NPs) coated with anti-CD2 antibody (Ab) to target both T cells and NK cells in lupus mice, identifying a key role of a population of TGF-β-producing NK cells in the induction of the CD4+ and CD8+ Foxp3+ Tregs that prevented disease.MethodsAnti-CD2 Ab-coated NPs made of polylactic-co-glycolic acid (PLGA) and encapsulating IL-2 or IL-2/TGF-β were used to inhibit a lupus-like disease characterized by a human anti-mouse graft versus host disease (GVHD) that develops after transfer of human PBMCs into immunodeficient NOD SCID mice.ResearchNPs containing only IL-2 protected mice from autoimmune disease similarly to NPs containing both IL-2 and TGF-β. Remarkably, the blockade of TGF-β signaling with an ALK-V inhibitor not only abolished the protective effects of the NPs but also reduced the survival of the diseased mice.ConclusionsIn the absence of TGF-β, IL-2 induces pathogenic T effector cells instead of promoting the induction of protective Tregs. This key role of TGF-β in the induction of Tregs has relevance for the ongoing clinical trials that employ low-dose IL-2 or IL-2 muteins in SLE and other autoimmune diseases to expand functional Tregs. Since lymphocyte production of TGF-β is decreased in SLE, our study suggests that in the immunotherapeutic management of SLE, one needs to correct the deficits of both IL-2 and TGF-β to optimally induce and expand functional Tregs.