Alterations in genes associated with cytosolic RNA sensing in whole blood are associated with coronary microvascular disease in SLE.

Systemic lupus erythematosus (SLE) patients are 90% women and over three times more likely to die of cardiovascular disease than women in the general population. Chest pain with no obstructive cardiac disease is associated with coronary microvascular disease (CMD), where narrowing of the small blood vessels can lead to ischemia, and frequently reported by SLE patients. Using whole blood RNA samples, we asked whether gene signatures discriminate SLE patients with coronary microvascular dysfunction (CMD) on cardiac MRI (n=4) from those without (n=7) and whether any signaling pathway is linked to the underlying pathobiology of SLE CMD. RNA-seq analysis revealed 143 differentially expressed (DE) genes between the SLE and healthy control (HC) groups, with virus defense and interferon (IFN) signaling being the key pathways identified as enriched in SLE as expected. We next conducted a comparative analysis of genes differentially expressed in SLE-CMD and SLE-non-CMD relative to HC samples. Our analysis highlighted differences in IFN signaling, RNA sensing and ADP-ribosylation pathways between SLE-CMD and SLE-non-CMD. This is the first study to investigate possible gene signatures associating with CMD in SLE, and our data strongly suggests that distinct molecular mechanisms underly vascular changes in CMD and non-CMD involvement in SLE.

Dexamethasone-Integrated Mesenchymal Stem Cells for Systemic Lupus Erythematosus Treatment via Multiple Immunomodulatory Mechanisms.

The therapeutic application of mesenchymal stem cells (MSCs) has good potential as a treatment strategy for systemic lupus erythematosus (SLE), but traditional MSC therapy still has limitations in effectively modulating immune cells. Herein, we present a promising strategy based on dexamethasone liposome-integrated MSCs (Dexlip-MSCs) for treating SLE via multiple immunomodulatory pathways. This therapeutic strategy prolonged the circulation time of dexamethasone liposomes in vivo, restrained CD4+T-cell proliferation, and inhibited the release of proinflammatory mediators (IFN-γ and TNF-α) by CD4+T cells. In addition, Dexlip-MSCs initiated cellular reprogramming by activating the glucocorticoid receptor (GR) signaling pathway to upregulate the expression of anti-inflammatory factors such as cysteine-rich secretory protein LCCL-containing domain 2 (CRISPLD2) and downregulate the expression of proinflammatory factors. In addition, Dexlip-MSCs synergistically increased the anti-inflammatory inhibitory effect of CD4+T cells through the release of dexamethasone liposomes or Dex-integrated MSC-derived exosomes (Dex-MSC-EXOs). Based on these synergistic biological effects, we demonstrated that Dexlip-MSCs alleviated disease progression in MRL/lpr mice more effectively than Dexlip or MSCs alone. These features indicate that our stem cell delivery strategy is a promising therapeutic approach for clinical SLE treatment.

NLRP3 inflammasome and its role in autoimmune diseases: A promising therapeutic target.

The NOD-like receptor protein 3 (NLRP3) inflammasome is a protein complex that regulates innate immune responses by activating caspase-1 and the inflammatory cytokines IL-1ß and IL-18. Numerous studies have highlighted its crucial role in the pathogenesis and development of inflammatory bowel disease, rheumatoid arthritis, systemic lupus erythematosus, autoimmune thyroid diseases, and other autoimmune diseases. Therefore, investigating the underlying mechanisms of NLRP3 in disease and targeted drug therapies holds clinical significance. This review summarizes the structure, assembly, and activation mechanisms of the NLRP3 inflammasome, focusing on its role and involvement in various autoimmune diseases. This review also identifies studies where the involvement of the NLRP3 inflammasome in the disease mechanism within the same disease appears contradictory, as well as differences in NLRP3-related gene polymorphisms among different ethnic groups. Additionally, the latest therapeutic advances in targeting the NLRP3 inflammasome for autoimmune diseases are outlined, and novel clinical perspectives are discussed. Conclusively, this review provides a consolidated source of information on the NLRP3 inflammasome and may guide future research efforts that have the potential to positively impact patient outcomes.

Mechanism of tacrolimus in the treatment of lupus nephritis.

Systemic lupus erythematosus (SLE) is a complex autoimmune disorder, with more than half of the patients developing lupus nephritis (LN), which significantly contributes to chronic kidney disease (CKD) and end-stage renal disease (ESRD). The treatment of lupus nephritis has always been challenging. Tacrolimus (TAC), an effective immunosuppressant, has been increasingly used in the treatment of LN in recent years. This review aims to explore the mechanisms of action of tacrolimus in treating LN. Firstly, we briefly introduce the pharmacological properties of tacrolimus, including its role as a calcineurin (CaN) inhibitor, exerting immunosuppressive effects by inhibiting T cell activation and cytokine production. Subsequently, we focus on various other immunomodulatory mechanisms of tacrolimus in LN therapy, including its effects on T cells, B cells, and immune cells in kidney. Particularly, we emphasize tacrolimus' regulatory effect on inflammatory mediators and its importance in modulating the Th1/Th2 and Th17/Treg balance. Additionally, we review its effects on actin cytoskeleton, angiotensin II (Ang II)-specific vascular contraction, and P-glycoprotein activity, summarizing its impacts on non-immune mechanisms. Finally, we summarize the efficacy and safety of tacrolimus in clinical studies and trials. Although some studies have shown significant efficacy of tacrolimus in treating LN, its safety remains a challenge. We outline the potential adverse reactions of long-term tacrolimus use and provide suggestions on effectively monitoring and managing these adverse reactions in clinical practice. In general, tacrolimus, as a novel immunosuppressant, holds promising prospects for treating LN. Of course, further research is needed to better understand its therapeutic mechanisms and ensure its safety and efficacy in clinical practice.

Left ventricular systolic function assessed by standard and advanced echocardiographic techniques in patients with systemic lupus erythematosus: A systemic review and meta-analysis.

Objectives: Aim of the study was to perform a systemic review and meta-analysis of the current case-control studies based on the assessment of the left ventricular (LV) systolic function with standard and advanced echocardiographic methods. Materials and methods: Objectives of the study, methods of statisticalanalysis, literature search strategy, inclusion andexclusion criteria, and outcome measurementswere defined according to Cochrane Collaborationsteps, 13 including recommendations for metaanalysisof observational studies in epidemiology (MOOSE). Results: A total of 850 papers were collected. Of those, eight papers (10 groups) including 174,442 SLE patients and 45,608,723 controls with heart failure (HF), 20 papers including 1,121 SLE patients and 1,010 controls with an evaluated LV ejection fraction (LVEF), and eight studies (nine groups) including 462 SLE patients and 356 controls with a measured LV global longitudinal strain (LVGLS) met the predefined inclusion criteria. HF rate in SLE patients was 2.39% (4,176 of 174,442 patients with HF), and SLE patients showed a 3.4 times higher risk for HF compared to controls. SLE patients had a lower LVEF compared to controls. LVGLS was more impaired in SLE patients compared to controls, irrespective of two-dimensional or three-dimensional speckle tracking echocardiography. Conclusion: Heart failure rate in SLE patients is high, and SLE patients showed a 3.4 times higher risk in patients with SLE compared to controls. LV systolic function, as measured by LVEF and LVGLS, is significantly affected in SLE patients, and LVGLS potentially represents a new tool for the early assessment of LV function.

Evaluation of depressive and anxiety symptoms in childhood-onset systemic lupus erythematosus: Frequency, course, and associated risk factors.

BACKGROUND: Depressive and anxiety symptoms are common in childhood-onset systemic lupus erythematosus (cSLE), yet their etiology and course remain unclear. We investigated the frequency of depressive and anxiety symptoms longitudinally in youth with cSLE, and associated socio-demographic and disease factors. METHODS: Participants 8-18 years with cSLE completed baseline measures [demographic questionnaire, Center for Epidemiologic Studies Depression Scale for Children (CES-DC), Screen for Childhood Anxiety Related Disorders (SCARED), and psychiatric interview] and follow-up measures (CES-DC and SCARED) > 6 months later. Prevalence of clinically significant depressive (score >15 on CES-DC) or anxiety symptoms (score ≥25 on SCARED) was calculated at baseline and follow-up. Baseline psychiatric interview diagnoses were tabulated. Relationships between socio-demographics (neighborhood-level material deprivation, ethnic concentration, adverse childhood event history, psychiatric condition in a first-degree relative), disease-related factors (disease duration, major organ disease, disease activity, glucocorticoid use, comorbid medical condition) and baseline depressive and anxiety scores, were examined in linear regression models. Factors with univariate associations with p < 0.2 were included in multivariable adjusted models. RESULTS: At baseline, of 51 participants with a mean disease duration of 4.3 years (SD 2.7), 35% (n = 18) and 35% (n = 18) had clinically significant depressive and anxiety symptoms, respectively. Anxiety disorder was diagnosed by psychiatric interview in 14% (n = 7), depressive disorders in 6% (n = 3), and post-traumatic stress disorder in 4% (n = 2). Adverse childhood events and first-degree relative with psychiatric condition were present in 40% (n = 20) and 37% (n = 18), respectively. In multivariable regression analysis, baseline depressive symptoms were positively correlated with neighbourhood-level material deprivation (ß = 4.2, 95% CI [1.0, 7.3], p = 0.01) and psychiatric condition in a first-degree relative (ß = 7.3, 95% CI [2.2, 12.4], p = 0.006). No associations were found between baseline anxiety scores and patient factors. At a median follow-up of 13.5 months (IQR 10.5, 18) for CES-DC (n = 34) and SCARED (n = 44), depressive and anxiety symptoms were persistent (18%, n = 6; 16%, n = 7), and newly present (24%, n = 8; 16% n = 7) at follow-up. CONCLUSION: In this sample, depressive and anxiety symptoms were prevalent and persistent. Depressive symptoms correlated with neighborhood-level material deprivation, and family psychiatric history. These findings support routine psychosocial assessment in cSLE, and provision of appropriate resources.

Sight-Threatening Unilateral Posterior Scleritis With Positive Atypical p-ANCA As Early Manifestation of Lupus Spectrum Disease.

Antinuclear cytoplasmic antibody (ANCA)-related scleritis is a potentially sight-threatening inflammatory condition that may occur as a primary vasculitis disorder or as a secondary vasculitis in a variety of inflammatory conditions. While ANCA has been classically associated with primary vasculitis diseases such as granulomatosis with polyangiitis (GPA), microscopic polyarteritis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA), it is interesting that in cases of lupus spectrum disease (LSD), both ANCA and atypical p-ANCA have been observed as secondary autoantibodies. Scleritis is a rare ocular manifestation of lupus disease with an incidence of around 1%. This paper describes a case of sight-threatening posterior scleritis with positive atypical p-ANCA as an early manifestation of LSD. LSD is an acknowledged condition but frequently presents a diagnostic challenge or delay due to its ambiguous symptoms which may not fully align with the classification criteria of established systemic lupus erythematosus (SLE). Nonetheless, this condition should not be underestimated due to its potential impact on major organ involvement and its tendency to progress to established SLE. The diagnosis of LSD heavily relies on clinician suspicion, considering factors such as symptoms present in at least one organ system, positivity of antinuclear antibody (ANA), and clinical suspicion of future SLE development. Early identification allows for early treatment which would benefit high-risk patients. A middle-aged Chinese lady presented with bilaterally asymmetrical eye redness and swelling, which was worse on the right side. Clinical examination revealed right eye proptosis, conjunctival injection, chemosis, scleral redness and binocular diplopia in all gazes. Right eye fundoscopic examination displayed extensive choroidal folds with a positive T-sign on the B-scan. Apart from ocular symptoms, there was no significant medical history related to autoimmune or connective tissue disorders. Her p-ANCA and c-ANCA results were negative, however atypical p-ANCA titer was positive with a high antinuclear antibody (ANA) titer of 1:1280 with a homogenous pattern. Additionally, she has a family history of systemic lupus erythematosus in her daughter. A diagnosis of right eye posterior scleritis secondary to underlying LSD was made. The scleritis was successfully treated with a combination of corticosteroid and systemic immunosuppressants and the patient was initiated on oral hydroxychloroquine to manage underlying LSD. We aim to highlight to clinicians the diagnostic challenges associated with scleritis in LSD and emphasize the importance of prompt and timely multidisciplinary management in minimizing patient mortality and morbidity, as reflected in this case. This case of a positive atypical p-ANCA scleritis in LSD serves as an excellent example of effective management.

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

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

A potential biomarker of disease activity in systemic lupus erythematosus, systemic immune-inflammation index.

OBJECTIVE: Biomarkers using routine laboratory tests accurately presenting systemic lupus erythematosus (SLE) disease activity may have important practical values in clinical settings. The primary purpose of this study was to investigate neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII; neutrophil X platelet/lymphocyte) as potential biomarkers of disease activity in cases with SLE. METHODS: In this case-control observational study, cases with SLE and demographically similar healthy controls were included. For clinical evaluation demographic features, disease duration and drugs were recorded. SLE clinical disease activity was assessed with SLEDAI scores. For laboratory assessments; erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and C3-C4 levels and anti-dsDNA positivity were recorded. Based on the simultaneous complete blood count (CBC) of the participants NLR, PLR and SII were calculated. The correlation between clinical and laboratory data was analyzed. RESULTS: 68 cases with SLE (64 women, 8 men) and 69 controls (65 women, 4 men) were included in this investigation. The demographic features of the cases and controls were similar. ESR, CRP, NLR, PLR and SII scores were statistically higher in cases with SLE than controls (p<0.000). Statistically significant positive correlations between SLEDAI and NLR, PLR and SII scores were demonstrated (p=0.01, r=0.505; 0.414; 0.698, respectively). We determined a cut-off value of SII as 681,3 presenting 77% sensitivity and 76% specificity to discriminate no-mild disease activity and moderate-higher SLE disease activity status. The SII cut-off value was determined as 681,3 presenting 77% sensitivity and 76% specificity (p<0.000, and AUC=0.930). CONCLUSION: CBC indices were shown to be higher in cases with SLE than healthy controls in our study. By presenting a strong correlation with disease activity and discriminating ability of disease status, SII might serve as a biomarker supporting clinical evaluation in SLE.

Headache in systemic lupus erythematosus: The LUNA registry cross-sectional study.

OBJECTIVES: This study investigated the clinically relevant factors for headaches in patients with systemic lupus erythematosus (SLE) using a registry from a Japanese multicenter cohort. METHODS: This cross-sectional study analysed the clinical information of patients with SLE who experienced headache episodes using the Migraine Disability Assessment (MIDAS) questionnaire. Significant findings in the comparisons between patients with headache (HA patients) and those without headache (non-HA patients) and in the comparisons depending on the grades of headache-induced disability in daily life based on the MIDAS scores were evaluated. Multivariate logistic regression analyses were performed to identify the relevant factors for headache. RESULTS: We analyzed 369 patients (median age, 45 years; female, 90.8%), including 113 HA patients who were significantly younger than non-HA patients (p < .005). HA patients had significantly higher frequencies of photosensitivity, rashes, and mucosal ulcers than non-HA patients (p < .05). Age and photosensitivity were significantly associated with headache (odds ratio (OR) 0.93, 95% confidence interval (CI) 0.95-0.99; OR 2.11, 95% CI 1.29-3.49, respectively). In the HA patients, hypocomplementemia was significantly associated with a disability of more than mild grade (OR 2.89, 95% CI 1.14-7.74), while rash was significantly observed in those presenting with moderate and severe disability. CONCLUSION: This study suggests that photosensitivity is a relevant manifestation of headache in patients with SLE. Persistent hypocomplementemia can contribute to headache-induced disability in daily life, whereas a rash may be a dominant manifestation in patients presenting with moderate/severe headache-induced disability.

Skin and ophthalmic complications of chloroquine and hydroxychloroquine in patients with rheumatoid arthritis and systemic lupus erythematous.

Immunosuppressive agents are routinely used to control autoimmunity. However, some adverse events are correlated to their clinical applications. The aim of this study was to study the clinical findings and ocular and cutaneous side effects of chloroquine (CQ) and hydroxychloroquine (HCQ), as current immunomodulators, in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). This descriptive study was performed on 360 individuals referred to the Rheumatology clinic during 2003-2020. Demographic characteristics and other information were collected from patients with RA and SLE. Skin and ocular complications were evaluated in patients who were on treatment with CQ and HCQ. Study populations consisted of 199 subjects with RA and 161 cases with SLE. The frequencies of skin and ocular complications in all patients treated with CQ and HCQ were 32 (17.65%) and 94 (51.9%), respectively. The prevalence of skin complications in patients with RA and SLE was 20 (10.05%) and 22 (13.66%), respectively. The frequencies of ocular complications in patients with RA and SLE were, respectively, 58 (29.4%) and 36 (22.5%). Multiple logistic regression analysis revealed that ophthalmic complications of CQ and HCQ in all patients were dependent on the effects of the duration of drug uses, disease duration, and cumulative doses (p < 0.05), unlike skin complications. Disease types had no effect on ocular complications. Based on these findings, treatment with CQ and HCQ participates in some skin and ocular complications in patients with RA and SLE which are largely associated with the duration of disease and treatment.

Clinical characteristics of systemic lupus erythematosus patients with adrenal hemorrhage.

INTRODUCTION: Adrenal hemorrhage (AH) is a rare condition and severe cases can lead to acute adrenal insufficiency with potentially life-threatening consequences. AH can be caused by a variety of etiologic factors, including systemic lupus erythematosus and antiphospholipid syndrome (APS). The early identification and treatment of these patients improves their prognosis. OBJECTIVE: The aims of this study were to analyze and summarize the clinical characteristics of systemic lupus erythematosus patients with AH. METHODS: The clinical characteristics of 6 systemic lupus erythematosus patients complicated with AH admitted to Peking Union Medical College Hospital and Beijing Shijitan Hospital from May 2004 to April 2022 were retrospectively analyzed. RESULTS: The diagnosis of AH was based on computed tomography (CT) findings. Two patients had bilateral lesions, and the other 4 patients had unilateral lesions. The symptoms of adrenal insufficiency were observed in 2 patients. The frequent presenting symptoms were abdominal pain, lower abdominal distension, vomiting, weakness, fever, arthrodynia, and skin rash. Four patients had APS. Five patients (4 patients with APS and 1 patient without APS) had thromboembolic events. All patients received glucocorticoid and immunosuppressant therapy. Five patients were treated with anticoagulant therapy. Follow-up imaging examinations showed a partial or total regression of the lesions after treatment. CONCLUSIONS: In the proper clinical setting, having high clinical suspicion for AH, early diagnosis and timely management is crucial to avoid life-threatening adrenal insufficiency. Key Points • AH is a rare condition and severe cases may lead to death. It can be caused by a variety of etiologic factors, including SLE. • In patients with SLE, especially combined with APS, if they complain of abdominal pain, particularly when common gastrointestinal involvement is difficult to explain, a high index of clinical suspicion is needed for the diagnosis of AH. • Early identification of AH in SLE patients can improve their prognosis.

Systemic correlates of cutaneous manifestations of lupus erythematosus.

BACKGROUND: We aimed to investigate the prevalence of skin disease among patients with systemic lupus erythematosus (SLE) and determine whether LE skin disease had clinical or serologic correlates with SLE. METHODS: We reviewed records of 335 patients with SLE (seen at Mayo Clinic, Rochester, Minnesota, USA) and abstracted skin manifestations, fulfilled mucocutaneous SLE criteria, and clinical and serologic parameters. RESULTS: Of the 231 patients with skin manifestations, 57 (24.7%) had LE-specific conditions, 102 (44.2%) had LE-nonspecific conditions, and 72 (31.2%) had both. LE skin disease was associated with photosensitivity, anti-Smith antibodies, and anti-U1RNP antibodies (all P < 0.001). Patients without LE skin disease more commonly had elevated C-reactive protein levels (P = 0.01). Patients meeting 2-4 mucocutaneous American College of Rheumatology criteria less commonly had cytopenia (P = 0.004) or anti-double-stranded DNA antibodies (P = 0.004). No significant associations were observed for systemic involvement (renal, hematologic, neurologic, and arthritis) when comparing patients with or without LE skin involvement. LE skin involvement was not significantly associated with internal SLE disease flare, number of medications, or overall survival. CONCLUSIONS: LE skin disease commonly occurs in patients with SLE. The presence of LE skin disease had no mitigating impact on the severity of SLE sequelae, disease flares, number of medications, or overall survival.

A rare case of non-lupus full house nephropathy in a transplanted kidney, case report.

Key Clinical Message: Non-lupus full house nephropathy is a rare entity that is still poorly understood. It can complicate post-transplant kidneys and result in a de novo process. Treatment is difficult but can be possibly achieved with optimization of immune suppression. Abstract: Non-lupus full house nephropathy is a rare entity with an unclear incidence. It describes the kidney biopsy findings of positive deposits for IgG, IgA, IgM, C3, and C1q on immunofluorescence in the absence of the classical diagnostic features of systemic lupus nephritis. This disease entity is becoming more recognized but further studies are still needed to evaluate the incidence, etiologies, and management of this condition. Transplant glomerulopathy is a major cause for renal graft loss. It can present with a wide variety of manifestations; it can cause AKI, CKD, or glomerular inflammations through an immune complex or autoimmune-mediated damage.

Relationship of serum and dietary vitamin D with high cardiometabolic risk in Mexican systemic lupus erythematosus patients: A cross-sectional study.

Objetive: Serum and dietary vitamin D could influence clinical disease activity and cardiometabolic outcomes in systemic lupus erythematosus (SLE). This study aimed to assess the relationship of serum and dietary vitamin D with cardiometabolic risk in Mexican SLE patients and healthy subjects (HS).Methods: 224 SLE patients and 201 HS were included in this cross-sectional study. Serum calcidiol was measured using a competitive enzyme-linked immunosorbent assay (ELISA). Vitamin D dietary intake was assessed by collecting three 24h food records. Dietary patterns (DPs) were identified using principal component analysis (PCA). Cardiometabolic status was analyzed through biochemical measurements and cardiometabolic indexes.Results: Calcidiol deficiency (<20 ng/mL) was associated with 1.66-fold higher risk of excess weight by body mass index (BMI) (≥25 kg/m2) (p = .02), 2.25-fold higher risk to low high-density lipoprotein-cholesterol (HDL-C) (<40 mg/dL) (p < .001), and 1.74-fold higher risk to high triglycerides (TG) ≥150 mg/dL (p = .02). Inadequate vitamin D dietary intake was associated with 1.92-fold higher risk of presenting non-healthy waist circumference (WC) (>80 cm) (p < .01), 2.05-fold higher risk of android waist to hip ratio (WHR ≥85) (p < .01), and 1.72-fold higher risk to excess weight (p = .02). Non-adherence to a DP rich in vitamin D food sources was associated with higher WC, WHR, triglycerides, and lower high-density lipoprotein-cholesterol (HDL-C); furthermore, in HS, non-adherence to the DP rich in vitamin D food sources provided 2.11-fold higher risk to calcidiol deficiency.In Cconclusion: A pattern of Calcidiol deficiency, inadequate vitamin D dietary intake, and non-adherence to a DP rich in vitamin D food sources was related to high cardiometabolic risk in SLE patients and HS.

Glymphatic abnormality in systemic lupus erythematosus detected by diffusion tensor image analysis along the perivascular space.

OBJECTIVES: This study aimed to evaluate the activity of the glymphatic system in systemic lupus erythematosus (SLE) by a diffusion-based method termed "Diffusion Tensor Image Analysis aLong the Perivascular Space (DTI-ALPS)", and examined its correlations with morphological changes in the brain. METHODS: In this cross-sectional study, forty-five female patients with SLE and thirty healthy controls (HCs) were included. Voxel-based and surface-based morphometric analyses were performed to examine T1 weighted images, and diffusion tensor images were acquired to determine diffusivity along the x-, y-, and z-axes in the plane of the lateral ventricle body. The ALPS-index was calculated. The differences in values between SLE patients and HC group were compared using the independent samples t test or Mann-Whitney U test. For the correlations between the ALPS-index and brain morphological parameters, partial correlation analysis and Pearson's correlation analysis were conducted. RESULTS: SLE patients showed lower values for the ALPS-index in left (1.543 ± 0.141 vs 1.713 ± 0.175, p < 0.001), right (1.428 ± 0.142 vs 1.556 ± 0.139, p < 0.001) and whole (1.486 ± 0.121 vs 1.635 ± 0.139, p < 0.001) brain compared with the HC group. The reduced ALPS-index showed significant positive correlations with gray matter loss. CONCLUSION: The non-invasive ALPS-index could serve as a sensitive and effective neuroimaging biomarker for individually quantifying glymphatic activity in patients with SLE. Glymphatic system abnormality may be involved in the pathophysiologic mechanism underlying central nervous system damage in SLE patients.

TNFSF13B rs9514828 C>T Polymorphism is Associated with Incidence of Atherosclerosis and Therapeutic Outcomes in Patients with Systemic Lupus Erythematosus.

Background: Systemic lupus erythematosus (SLE) is a complex autoimmune disease with numerous clinical manifestations. Organ involvement can aggravate patients with SLE and cause comorbidities such as atherosclerosis. Recently, the TNFSF13B gene has been found to be linked with SLE events. This study aimed to analyze the association between single nucleotide polymorphisms of the TNFSF13B rs9514828 with incidence of atherosclerosis and therapeutic outcomes in patients with SLE. Patients and Methods: This case-control study included 84 SLE patients, of whom 21 patients with SLE with atherosclerosis and 63 patients with SLE without atherosclerosis. Using enzyme-linked immunosorbent assay method, interleukin-6 and interferon gamma levels were quantified. The TNFSF13B gene polymorphism was evaluated using polymerase chain reaction followed by sequencing. The lupus low disease activity state (LLDAS) criteria were used to measure the therapeutic outcomes. Statistical analysis was conducted using binary logistic regression. Results: The genetic variations of TNFSF13B rs9514828 were CC = 35, CT = 41, and TT = 8. There was an association between TNFSF13B rs9514828 C>T polymorphism in patients with SLE with and without atherosclerosis (p = 0.03; odds ratio (OR) 4.72, 95% confidence interval [CI] 1.22-18.37). Furthermore, the TNFSF13B rs9514828 C>T polymorphism had association with the therapeutic outcomes of patients with SLE who manifested with LLDAS (p = 0.00; OR 7.58, 95% CI 2.61-21.99). Conclusion: The association of TNFSF13B rs9514828 C>T polymorphism and incidence of atherosclerosis as well as the therapeutic outcomes in patients with SLE indicate the potential utility of the gene variation as screening tool to employ personalized medicine to undertake preventive measures in order to prevent atherosclerosis and to predict a poor prognosis in SLE patient.

Genetically Proxied Autoimmune Diseases and the Risk of Facial Aging.

Purpose: Previous studies have suggested a relationship between autoimmune diseases and the risk of facial skin aging. However, evidence from population-based studies on this topic is limited, leaving the causal association between these factors unknown. This study aimed to systematically evaluate the causal effects of 18 autoimmune diseases on the risk of facial skin aging, aim of providing strategies to mitigate early facial aging in patients with autoimmune diseases. Patients and Methods: We conducted univariate Mendelian randomization (UVMR) analyses to examine the causal relationship between 18 autoimmune diseases and facial aging using publicly available summary data from genome-wide association studies (GWASs). We also conducted multivariate Mendelian randomization (MVMR) analyses to adjust for confounding factors, including smoking, alcohol consumption, and body mass index (BMI). Results: The main inverse variance weighted (IVW) method revealed that genetically proxied ankylosing spondylitis (AS) (OR 1.017; 95% CI: 1.003-1.031; P=0.018), sicca syndrome (SS) (OR 1.008; 95% CI: 1.005-1.011; P= 2.66×10-6), systemic lupus erythematosus (SLE) (OR 1.006; 95% 1.001-1.011; P=0.014), multiple sclerosis (MS) (OR 1.004; 95% CI: 1.001-1.007; P=0.021), primary sclerosing cholangitis (PSC) (OR 1.002; 95% CI: 1.000-1.004; P=0.023), and celiac disease (CeD) (OR 1.002; 95% CI: 1.001-1.004; P=0.009) were significantly associated with higher risk of facial aging. After adjusting for potential confounding factors, the association persisted between AS, SLE, and CeD. Conclusion: These findings indicated that autoimmune diseases play a causal role in facial skin aging. Therefore, patients with autoimmune diseases should take appropriate measures to prevent early facial aging.

Coexistence of Allergic Diseases in Pediatric Systemic Lupus Erythematosus Patients: Prevalence, Clinical manifestation and Severity.

Objective. This study aimed to evaluate allergic diseases in pediatric patients with SLE and their association with SLE disease activity. Method. Patients with SLE aged ≤18 years were enrolled. Allergic diseases were screened using the International Study of Asthma and Allergies in Childhood questionnaire. Patients with a positive allergic disease screen were evaluated by a pediatric allergist for diagnostic confirmation and severity assessment. Results. Out of 118 patients, 16 patients (13.56%) were confirmed to have 1 or more allergic diseases; fourteen with allergic rhinitis, 4 with asthma, and 2 with atopic dermatitis. Two patients had severe-persistent allergic rhinitis and one patient had undiagnosed, uncontrolled severe asthma. No statistically significant correlations between the severity of allergic diseases and SLE disease activity were identified. Conclusions. The overall prevalence of allergic disease among pediatric patients with SLE is within the range of the general population. Severe and undiagnosed allergic diseases and SLE can coexist.

Navigating the diagnostic maze: A case presentation of C1q vasculitis mimicking hypocomplementemic urticarial vasculitis in a patient with systemic lupus erythematosus.

In rare instances, patients with SLE may exhibit atypical clinical manifestations, such as Hypocomplementemic Urticarial Vasculitis, which can pose diagnostic challenges. Here, we present a case report of a 28-year-old female with a history of SLE with lupus nephritis clase IV who developed HUV-like symptoms, ultimately leading to a diagnosis of C1q Vasculitis. This case underscores the importance of considering C1q Vasculitis in SLE patients presenting with HUV-like features and highlights Rituximab as a promising therapeutic option for managing this rare condition.