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ObjectiveAccurate identification of lupus nephritis (LN) cases is essential for patient management, research and public health initiatives. However, LN diagnosis codes in electronic health records (EHRs) are underused, hindering efficient identification. We investigated the current performance of International Classification of Diseases (ICD) codes, 9th and 10th editions (ICD9/10), for identifying prevalent LN, and developed scoring systems to increase identification of LN that are adaptable to settings with and without LN ICD codes.MethodsTraining and test sets derived from EHR data from a large health system. An external set comprised data from the EHR of a second large health system. Adults with ICD9/10 codes for SLE were included. LN cases were ascertained through manual chart reviews conducted by rheumatologists. Two definitions of LN were used: strict (definite LN) and inclusive (definite, potential or diagnostic uncertainty). Gradient boosting models including structured EHR fields were used for predictor selection. Two logistic regression-based scoring systems were developed ('LN-Code' included LN ICD codes and 'LN-No Code' did not), calibrated and validated using standard performance metrics.ResultsA total of 4152 patients from University of California San Francisco Medical Center and 370 patients from Zuckerberg San Francisco General Hospital and Trauma Center met the eligibility criteria. Mean age was 50 years, 87% were female. LN diagnosis codes demonstrated low sensitivity (43-73%) but high specificity (92-97%). LN-Code achieved an area under the curve (AUC) of 0.93 and a sensitivity of 0.88 for identifying LN using the inclusive definition. LN-No Code reached an AUC of 0.91 and a sensitivity of 0.95 (0.97 for the strict definition). Both scoring systems had good external validity, calibration and performance across racial and ethnic groups.ConclusionsThis study quantified the underutilisation of LN diagnosis codes in EHRs and introduced two adaptable scoring systems to enhance LN identification. Further validation in diverse healthcare settings is essential to ensure their broader applicability.

Mitochondria are eukaryotic cellular organelles that function in energy metabolism, ROS production, and programmed cell death. Cutaneous epithelial and hair follicle dermal papilla cells are energy-rich cells that thereby may be affected by mitochondrial dysfunction and DNA mutation accumulation. In this review, we aimed to summarize the medical literature assessing dermatologic conditions and outcomes associated with mitochondrial dysfunction. A search of PubMed and Embase was performed with subsequent handsearching to retrieve additional relevant articles. Mitochondrial DNA (mtDNA) deletions, mutation accumulation, and damage are associated with phenotypic signs of cutaneous aging, hair loss, and impaired wound healing. In addition, several dermatologic conditions are associated with aberrant mitochondrial activity, such as systemic lupus erythematosus, psoriasis, vitiligo, and atopic dermatitis. Mouse model studies have better established causality between mitochondrial damage and dermatologic outcomes, with some depicting reversibility upon restoration of mitochondrial function. Mitochondrial function mediates a variety of dermatologic conditions, and mitochondrial components may be a promising target for therapeutic strategies.

BackgroundSocial determinants of health are consistently associated with systemic lupus erythematosus (SLE) outcomes. However, social determinants of health are typically measured with conventional socioeconomic status factors such as income or education. We assessed the association of economic insecurities (ie, food, housing, health care, and financial insecurity) with patient-reported outcomes in a cohort of patients with SLE.MethodsIn this cross-sectional analysis, data were derived from the California Lupus Epidemiology Study based in the San Francisco Bay Area, CA, USA. Participants were recruited between Feb 25, 2015, and Jan 10, 2018, from rheumatology clinics. Inclusion criteria were Bay Area residency; oral fluency in English, Spanish, Cantonese, or Mandarin; 18 years or older; ability to provide informed consent; and a physician confirmed SLE diagnosis. Food, housing, health care, and financial economic insecurities were assessed by validated screening tools. Patient-reported outcomes were obtained using PROMIS, Quality of Life in Neurological Disorders (known as Neuro-QoL) Cognitive Function short form, Patient Health Questionnaire (PHQ)-8, and General Anxiety Disorder (GAD)-7 instruments. Poverty was defined as household income of 125% or less of the federal poverty limit. Lower education was defined as less than college-graduate education. The association of economic insecurities with patient-reported outcomes was assessed by multivariable linear regression models adjusting for demographics, SLE disease characteristics, and comorbidities. We tested for interactions of insecurities with poverty and education.FindingsThe final cohort included 252 participants. Mean age was 49·7 (SD 13·4) years, 228 (90%) of 252 were women and 24 (10%) were men. 80 (32%) individuals self-identified as Asian, 26 (10%) as Black, 101 (40%) as White, eight (3%) as mixed race, and 37 (15%) as other race; 59 (23%) self-identified as Hispanic. 135 (54%) individuals had at least one insecurity. Insecurities were highly prevalent, and more common in those with poverty and lower education. Adjusted multivariate analyses revealed that participants with any insecurity had significantly worse scores across all measured patient-reported outcomes. For physical function, no insecurity had an adjusted mean score of 48·9 (95% CI 47·5-50·3) and any insecurity had 45·7 (44·3-47·0; p=0·0017). For pain interference, no insecurity was 52·0 (50·5-53·5) and any insecurity was 54·4 (53·0-55·8; p=0·031). For fatigue, no insecurity was 50·5 (48·8-52·3) and any insecurity was 54·9 (53·3-56·5; p=0·0005). For sleep disturbance, no insecurity was 49·9 (48·3-51·6) and any insecurity was 52·9 (51·4-54·5; p=0·012). For cognitive function, no insecurity was 49·3 (47·7-50·9) and any insecurity was 45·6 (44·1-47·0; p=0·0011). For PHQ-8, no insecurity was 4·4 (3·6-5·1) and any insecurity was 6·1 (5·4-6·8; p=0·0013). For GAD-7, no insecurity was 3·3 (2·6-4·1) and any insecurity was 5·2 (4·5-5·9; p=0·0008). Individuals with more insecurities had worse patient-reported outcomes. There were no statistically significant interactions between insecurities and poverty or education.InterpretationHaving any economic insecurity was associated with worse outcomes for people with SLE regardless of poverty or education. The findings of this study provide insight into the relationship between economic insecurities and SLE outcomes and underscore the need to assess whether interventions that directly address these insecurities can reduce health disparities in SLE.FundingUS Centers for Disease Control, Rheumatology Research Foundation, and National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Lupus nephritis (LN) is a pathologically heterogenous autoimmune disease linked to end-stage kidney disease and mortality. Better therapeutic strategies are needed as only 30%-40% of patients completely respond to treatment. Noninvasive biomarkers of intrarenal inflammation may guide more precise approaches. Because urine collects the byproducts of kidney inflammation, we studied the urine proteomic profiles of 225 patients with LN (573 samples) in the longitudinal Accelerating Medicines Partnership in RA/SLE cohort. Urinary biomarkers of monocyte/neutrophil degranulation (i.e., PR3, S100A8, azurocidin, catalase, cathepsins, MMP8), macrophage activation (i.e., CD163, CD206, galectin-1), wound healing/matrix degradation (i.e., nidogen-1, decorin), and IL-16 characterized the aggressive proliferative LN classes and significantly correlated with histological activity. A decline of these biomarkers after 3 months of treatment predicted the 1-year response more robustly than proteinuria, the standard of care (AUC: CD206 0.91, EGFR 0.9, CD163 0.89, proteinuria 0.8). Candidate biomarkers were validated and provide potentially treatable targets. We propose these biomarkers of intrarenal immunological activity as noninvasive tools to diagnose LN and guide treatment and as surrogate endpoints for clinical trials. These findings provide insights into the processes involved in LN activity. This data set is a public resource to generate and test hypotheses and validate biomarkers.

Neutrophilic dermatoses (NDs) refer to a group of cutaneous conditions histologically characterized by the dense accumulation of neutrophils in the skin in the absence of infection. NDs have been associated with underlying autoimmune connective tissue disorders (CTDs) such as systemic lupus erythematosus (SLE), Sjogren's syndrome, and dermatomyositis. We describe a case of neutrophilic dermatoses as a manifestation of a SLE flare.

This study focuses on understanding the transcriptional heterogeneity of activated platelets and its impact on diseases such as sepsis, COVID-19, and systemic lupus erythematosus (SLE). Recognizing the limited knowledge in this area, our research aims to dissect the complex transcriptional profiles of activated platelets to aid in developing targeted therapies for abnormal and pathogenic platelet subtypes. We analyzed single-cell transcriptional profiles from 47,977 platelets derived from 413 samples of patients with these diseases, utilizing Deep Neural Network (DNN) and eXtreme Gradient Boosting (XGB) to distinguish transcriptomic signatures predictive of fatal or survival outcomes. Our approach included source data annotations and platelet markers, along with SingleR and Seurat for comprehensive profiling. Additionally, we employed Uniform Manifold Approximation and Projection (UMAP) for effective dimensionality reduction and visualization, aiding in the identification of various platelet subtypes and their relation to disease severity and patient outcomes. Our results highlighted distinct platelet subpopulations that correlate with disease severity, revealing that changes in platelet transcription patterns can intensify endotheliopathy, increasing the risk of coagulation in fatal cases. Moreover, these changes may impact lymphocyte function, indicating a more extensive role for platelets in inflammatory and immune responses. This study identifies crucial biomarkers of platelet heterogeneity in serious health conditions, paving the way for innovative therapeutic approaches targeting platelet activation, which could improve patient outcomes in diseases characterized by altered platelet function.

Arsenic trioxide (ATO) is now part of the standard regimen for the treatment of newly diagnosed and relapsed acute promyelocytic leukemia. The availability of an oral form of ATO has greatly reduced the incidence of cardiotoxicity as compared to intravenous (IV) administration. Increasing evidence suggests that ATO has anti-inflammatory properties that may be useful for the treatment of autoimmune diseases. These include the modulation of Treg cell activation, Th1/Th2 and Th17/Treg balance, depletion of activated T cells and plasmacytoid dendritic cells, and influence of B-cell differentiation, leading to reduced autoantibody and cytokine production. ATO has also been shown to induce apoptosis of activated fibroblast-like synoviocytes through the generation of reactive oxygen species and alter the gut microbiota in collagen-induced arthritis. Despite the emergence of newer treatment modalities, the treatment of systemic lupus erythematosus (SLE), especially refractory manifestations, remains a challenge, owing to the paucity of effective biological and targeted therapies that are devoid of adverse effects. Oral ATO is an attractive option for the treatment of SLE because of the lower cost of production, convenience of administration, and reduced cardiotoxicity. This article summarizes the anti-inflammatory mechanisms of ATO and its potential application in the treatment of SLE and other rheumatic diseases. [ABSTRACT FROM AUTHOR]

Aim: To compare pregnancy outcomes between IA and non IA lupus patients. Background: Pregnancy in lupus patients confers an increased risk of maternal and fetal morbidity. There are no data on pregnancy outcomes for indigenous Australian (IA) patients with lupus. Methods: Using state‐wide longitudinal hospital morbidity data, we studied 702 pregnancies in IA (n = 31) and non‐indigenous (NI) patients with lupus (n = 357) in Western Australia and compared rates for live birth (LB), preterm birth (PB) and gestational complications in the period 1985–2015. Results are presented as medians or frequency. Results: IA patients had proportionally more pre‐existing renal disease (35 vs 13%, P < 0.01) and lower socio‐economic status (P = 0.02). Age at first pregnancy was lower in IA patients (27 vs 30 years, P < 0.001), recorded gravidity was similar (2 vs 2, P > 0.6) and elective termination (n = 138) was more frequent in NI than IA pregnancies (21.1 vs 4.8%, P < 0.01). For continued pregnancies (59 in IA and 505 in NI), respective outcomes were as follows: LB 84.7% versus 91.5% (P = 0.15), spontaneous abortion 13.5% versus 6.9% (P = 0.13), (pre‐)eclampsia 8% versus 9.9% (P = 0.89), PB 12% versus 13.4% (P = 0.98) and caesarean delivery 30% versus 47.2% (P = 0.02). Gestational diabetes (26% vs 6.1%), renal flares (20% vs 5.6%) and infections (22% vs 6.3%) were all more frequent in IA lupus pregnancies (all P < 0.001). Conclusions: The burden of comorbidities was higher in IA patients with lupus due to renal flares, gestational DM and infections. Although PB rates were overall high, they were, however, similar for IA and NI lupus pregnancies, as were LB rates. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) remains the number one cause of death worldwide. Women are at increased risk of death from CVD, but the mechanisms for how and why this occurs remain elusive. One subset of women who are exceptionally vulnerable to CVD are those with rheumatic diseases (RDs). Indeed, women account for 80% of all RDs, disorders that encompass a broad range of autoimmune and autoinflammatory diseases that lead to chronic inflammation and pathology. The clear association of increased CVD risk in women with RD is thought to be mediated by a number of factors, including RD pathology itself, pharmacological induction of CVD, and/or as yet unidentified mechanisms. As such, elucidation of the causes and treatments of these pathologies has given rise to a new subspecialty of cardiology: cardio-rheumatology. Here, we review and discuss the CVD risks in patients with RDs, the associated sex disparities in RD and CVD care, as well as the current therapeutic and interventional options available to specifically help women with RDs. We hope this discussion will provide guidance and support to patients, as well as to cardio-rheumatologists, as these groups are the most uniquely positioned to radically improve CVD care in these individuals. Moreover, we are hopeful this discussion may lead to better, more efficacious approaches to treating these disorders in women in the near future. [ABSTRACT FROM AUTHOR]

This article discusses the relationship between Tlr5 deficiency and lupus-like disease in mice. The study found that Tlr5 deficiency actually worsened lupus symptoms in female mice, leading to increased proteinuria and glomerulonephritis. The study suggests that Tlr5 deficiency may modulate host-microbiota interactions to exacerbate lupus. Additionally, the article provides a list of references to various scientific articles related to the gut microbiota and its potential role in autoimmune diseases, specifically lupus. [Extracted from the article]

Summary: Systemic lupus erythematosus is a complex autoimmune disease resulting from a dysregulation of the immune system that involves gut dysbiosis and an altered host cellular metabolism. This review highlights novel insights and expands on the interactions between the gut microbiome and the host immune metabolism in lupus. Pathobionts, invasive pathogens, and even commensal microbes, when in dysbiosis, can all trigger and modulate immune responses through metabolic reprogramming. Changes in the microbiota's global composition or individual taxa may trigger a cascade of metabolic changes in immune cells that may, in turn, reprogram their functions. Factors contributing to dysbiosis include changes in intestinal hypoxia, competition for glucose, and limited availability of essential nutrients, such as tryptophan and metal ions, all of which can be driven by host metabolism changes. Conversely, the accumulation of some host metabolites, such as itaconate, succinate, and free fatty acids, could further influence the microbial composition and immune responses. Overall, mounting evidence supports a bidirectional relationship between host immunometabolism and the microbiota in lupus pathogenesis. [ABSTRACT FROM AUTHOR]

Objective The objective of this study was to assess the prevalence and characteristics of, and knowledge about, photosensitivity and the use of photoprotective measures in an international cohort of cutaneous lupus erythematosus and SLE patients. Methods We conducted an international, cross-sectional study based on a 46-question web-based survey, including patients with medically confirmed lupus erythematosus, conducted between November 2021 and April 2022. Results A total of 600 patients with lupus erythematosus [94% female, median age: 41 years, interquartile range (IQR): 33–51] from 50 countries were included. A history of photosensitivity was reported by 389/600 (64.8%) patients. Photosensitivity was associated with the presence of other cutaneous involvement [odds ratio (OR) = 3.8; 95% CI 2.5–5.7; P  < 0.001] and differed according to the area of residence and level of education (P  < 0.001, for all). Photosensitivity was characterized by a wide range of clinical manifestations (both cutaneous and systemic symptoms in 56.1% and systemic symptoms only in 29.8% of patients). Fatigue was the most frequently reported systemic manifestation (82.3%). Overall, 559/600 (93%) patients were aware of the detrimental role of ultraviolet radiation exposure in lupus erythematosus, but 160/480 (33.3%) were unaware of the importance of photoprotective measures, including 90/310 (29%) among those with photosensitivity. Conclusion A high rate of self-reported photosensitivity characterizes lupus erythematosus patients. Photosensitivity frequently includes subjective features, which makes it difficult to evaluate in clinical practice. As fatigue is frequent in lupus erythematosus, further study is needed to clarify the causal link with ultraviolet radiation exposure. About one-third of lupus erythematosus patients are unaware of the importance of photoprotective measures. This should be improved through more frequent and targeted awareness interventions. [ABSTRACT FROM AUTHOR]

Background and Objective: Chronic interstitial lung disease (ILD) occurs rarely with systemic lupus erythematosus (SLE) as compared with other connective tissue diseases. This multicentric retrospective study of patients with SLE‐ILD from the OrphaLung and French SLE networks during 2005–2020 aimed to describe the characteristics of patients with SLE‐ILD and analyse factors associated with prognosis. Methods: We analysed data for 89 patients with SLE‐ILD (82 women, 92.1%) (median age at SLE diagnosis: 35 years [interquartile range 27–47]). All patients met the 2019 EULAR/ACR criteria for the diagnosis of SLE. Results: Forty two (47.2%) patients were positive for anti‐ribonuclear protein antibodies and 45 (50.6%) for anti SSA/Ro antibodies. A total of 58 (65.2%) patients had another connective tissue disease: Sjögren's syndrome (n = 33, 37.1%), systemic sclerosis (n = 14, 15.7%), inflammatory myopathy (n = 6, 6.7%), or rheumatoid arthritis (n = 6, 6.7%). ILD was diagnosed along with SLE in 25 (28.1%) patients and at a median of 6 (0–14) years after the SLE diagnosis. The most frequent CT pattern was suggestive of non‐specific interstitial pneumonia (n = 41, 46.0%) with or without superimposed organizing pneumonia. After a median follow‐up of 86.5 [39.5–161.2] months, 18 (20.2%) patients had died and 6 (6.7%) underwent lung transplantation. The median 5‐year and 10‐year transplantation‐free survival were 96% (92–100) and 87% (78–97). In total, 44 (49.4%) patients showed ILD progression. Cutaneous manifestations and Raynaud's phenomenon were associated with better survival. Only forced vital capacity was significantly associated with survival and ILD progression. Conclusion: ILD is a rare manifestation of SLE with good overall prognosis but with possible risk of ILD progression. Patients with SLE‐ILD frequently have another connective tissue disease. [ABSTRACT FROM AUTHOR]

This article discusses a study that examined the relationship between discoid lupus erythematosus (DLE) and various demographic and health factors. The researchers analyzed data from the All of Us Research Program and found that DLE patients had higher odds of having concurrent diagnoses in various domains, including cardiovascular, autoimmune, endocrine, renal, psychiatric, and dermatologic. The study also found that LGBTQ individuals had a lower prevalence of DLE, suggesting potential social or healthcare barriers. Lower income levels and higher prevalence of insurance were also associated with DLE. The study emphasizes the need for further research to explore these disparities and understand the impact of stress and access to healthcare services. [Extracted from the article]

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. Plain language summary: Skin manifestations of systemic lupus erythematosus (SLE) are myriad and can have a dramatic impact on patients' lives. Our study at Mayo Clinic, Rochester/Minnesota, USA, investigated the range of skin disease that occurs in patients with SLE and showed that these skin manifestations require as much systemic treatment comparable to those used for other organs affected by SLE in patients without skin findings. Patients with skin manifestations did not have better survival than those without skin manifestations. Our study highlights the important role of dermatologists in the care of patients with SLE and in SLE research. [ABSTRACT FROM AUTHOR]

Objective. Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a wide spectrum of clinical manifestations. A decision aid (DA) for SLE was developed and implemented in 15 rheumatology clinics throughout the United States. This study explored the experiences of patients who viewed the DA to understand how patients engage with and respond to the SLE DA. Methods. We conducted a qualitative descriptive study using semistructured interviews with a convenience sample of 24 patients during May to July 2022. Results. Patients recognized the value of the SLE DA in providing general knowledge about SLE and different treatment options. However, patients expressed a desire for more comprehensive lifestyle information to better manage their condition. Another theme was the importance of having multiple formats available to cater to their different needs, as well as tailoring the DA to different stages of SLE. Conclusion. This study contributes to a broader understanding of how to provide patient-centered care for patients with SLE by offering practical insights that can inform the development of more effective, patient-centric health information technologies for managing chronic diseases, ultimately improving patient outcomes. Overall, this study underscores the significance of optimizing both the information content and determining the appropriate delivery of the tool for its future sustainability. [ABSTRACT FROM AUTHOR]

Introduction: Leaky gut has been linked to autoimmune disorders including lupus. We previously reported upregulation of anti-flagellin antibodies in the blood of lupus patients and lupus-prone mice, which led to our hypothesis that a leaky gut drives lupus through bacterial flagellin-mediated activation of toll-like receptor 5 (TLR5). Methods: We created MRL/lpr mice with global Tlr5 deletion through CRISPR/Cas9 and investigated lupus-like disease in these mice. Result: Contrary to our hypothesis that the deletion of Tlr5 would attenuate lupus, our results showed exacerbation of lupus with Tlr5 deficiency in female MRL/lpr mice. Remarkably higher levels of proteinuria were observed in Tlr5-/- MRL/lpr mice suggesting aggravated glomerulonephritis. Histopathological analysis confirmed this result, and Tlr5 deletion significantly increased the deposition of IgG and complement C3 in the glomeruli. In addition, Tlr5 deficiency significantly increased renal infiltration of Th17 and activated cDC1 cells. Splenomegaly and lymphadenopathy were also aggravated in Tlr5-/- MRL/lpr mice suggesting impact on lymphoproliferation. In the spleen, significant decreased frequencies of regulatory lymphocytes and increased germinal centers were observed with Tlr5 deletion. Notably, Tlr5 deficiency did not change host metabolism or the existing leaky gut; however, it significantly reshaped the fecal microbiota. Conclusion: Global deletion of Tlr5 exacerbates lupus-like disease in MRL/lpr mice. Future studies will elucidate the underlying mechanisms by which Tlr5 deficiency modulates host-microbiota interactions to exacerbate lupus. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE, lupus) is a debilitating, multisystem autoimmune disease that can affect any organ in the body. The disease is characterized by circulating autoantibodies that accumulate in organs and tissues, which triggers an inflammatory response that can cause permanent damage leading to significant morbidity and mortality. Lyn, a member of the Src family of non-receptor protein tyrosine kinases, is highly implicated in SLE as remarkably both mice lacking Lyn or expressing a gain-of-function mutation in Lyn develop spontaneous lupus-like disease due to altered signaling in B lymphocytes and myeloid cells, suggesting its expression or activation state plays a critical role in maintaining tolerance. The past 30 years of research has begun to elucidate the role of Lyn in a duplicitous signaling network of activating and inhibitory immunoreceptors and related targets, including interactions with the interferon regulatory factor family in the toll-like receptor pathway. Gain-offunction mutations in Lyn have now been identified in human cases and like mouse models, cause severe systemic autoinflammation. Studies of Lyn in SLE patients have presented mixed findings, which may reflect the heterogeneity of disease processes in SLE, with impairment or enhancement in Lyn function affecting subsets of SLE patients that may be a means of stratification. In this review, we present an overview of the phosphorylation and protein-binding targets of Lyn in B lymphocytes and myeloid cells, highlighting the structural domains of the protein that are involved in its function, and provide an update on studies of Lyn in SLE patients. [ABSTRACT FROM AUTHOR]

Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease that often requires hospitalization. Most hospitalizations are due to infections and/or disease activity, for which several risk factors have been described in non-Mestizo patients. Objective: To identify risk factors for hospitalization in patients with systemic lupus erythematosus (SLE). Methods: This was an observational case-control study of patients with SLE in San Luis Potosí, Mexico, evaluated from January 2019 to October 2020. We compared hospitalized lupus patients with non-hospitalized lupus patients. We used descriptive statistics and logistic regression to describe potential risk factors. Results: Of a total of 202 patients, 89 (45.1%) were hospitalized; these patients were younger, had shorter disease duration, higher disease activity scores (systemic lupus erythematosus disease activity index-SLEDAI), and more accumulated damage than non-hospitalized patients. The primary reasons for hospitalization were disease activity (60.7%), kidney disease, infection, and drug toxicity (5.6%). Multivariate analysis revealed several risk factors associated with hospitalization, including elevated creatinine, C-reactive protein, neutrophil levels, and constitutional symptoms, while prolonged international normalized ratio (INR), longer stay in the intensive care unit (ICU), and vasopressor use were associated with mortality. The use of antimalarials was a protective factor against hospitalization. Survival analysis revealed that patients with hospital-acquired infections had a lower probability of survival. Conclusions: Disease activity was the most common reason for hospitalization; kidney, constitutional, and hematological factors were associated with hospitalization; and the use of antimalarial was a protective factor for hospitalization. [ABSTRACT FROM AUTHOR]

Objectives Taxifolin (dihydroquercetin) is a bioactive plant flavonoid that exhibits anti-inflammatory and anti-oxidative properties. We hypothesized that taxifolin might be an effective dietary supplement to ameliorate symptoms arising from thrombo-inflammatory diseases such as lupus and APS. Methods We used in vitro assays and a mouse model to determine mechanisms by which taxifolin inhibits neutrophil extracellular trap (NET) formation (i.e. NETosis) and venous thrombosis in lupus and APS. Results At doses ranging from 0.1 to 1 µg/ml, taxifolin inhibited NETosis from control neutrophils stimulated with autoantibodies isolated from lupus and APS patients, and its suppressive effects were mitigated by blocking the antioxidant transcription factor Nrf2 (nuclear factor erythroid 2–related factor 2). Furthermore, taxifolin at a dose as low as 20 mg/kg/day reduced in vivo NETosis in thrombo-inflammatory mouse models of lupus and APS while also significantly attenuating autoantibody formation, inflammatory cytokine production and large-vein thrombosis. Conclusion Our study is the first to demonstrate the protective effects of taxifolin in the context of lupus and APS. Importantly, our study also suggests a therapeutic potential to neutralize neutrophil hyperactivity and NETosis that could have relevance to a variety of thrombo-inflammatory diseases. [ABSTRACT FROM AUTHOR]

The cyclic GMP–AMP synthase (cGAS), a prominent intracellular DNA sensor in mammalian cells, controls the innate immune response and the stimulator of interferon genes (STING)‐mediated synthesis of pro‐inflammatory cytokines, such as type‐I interferon (IFN‐I). For decades, IFN‐I has been hypothesized to be essential in the development of systemic lupus erythematosus (SLE), a chronic multisystem autoimmunity characterized by immune complex (IC) deposition in small vessels. Recent findings revealed that the activation of the cGAS–STING pathway by self‐DNA would propagate the autoimmune responses via upregulating IFN‐I production in SLE. In this review, we aimed to provide a comprehensive outlook of the role of the cGAS–STING pathway in SLE pathobiology, as well as, a better understanding of current therapeutic opportunities targeting this axis. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Systemic Lupus Erythematosus (SLE) can have an insidious onset and a fatal prognosis in children. Patients presenting without typical signs of SLE should undergo further evaluation if they are not responding to the initial diagnosis and treatment. This is especially true for patients with rapidly progressing symptoms and deterioration in spite of treatment. Pediatric Systemic Lupus Erythematosus is a chronic autoimmune disorder with various organ involvement pulmonary involvement in the course of this disorder is a rare yet potentially life‐threatening complication. In this case report we highlight the findings of a 16‐year‐old girl acutely and initially presenting with cough and fever, eventually complicating to diffuse alveolar hemorrhage and gradual loss of consciousness. Although the patient was started on immunosuppressive treatment after the diagnosis of lupus, based on renal and hematological impairment, was made and initially responded, she eventually deteriorated. [ABSTRACT FROM AUTHOR]

Background: Despite accumulating evidence correlating oxidative stress with lupus disease activity, the brain redox pathways are still poorly investigated. Cinnamomum cassia, a widely used spice with powerful antioxidant properties, could be a novel therapeutic candidate in lupus. Methods: C57BL/6J female mice were divided into five groups: sham, sham-cinnamon, lupus, lupus-cinnamon starting from induction, and lupus-cinnamon starting two weeks before induction. Lupus was induced by skin application on the right ear with 1.25 mg of 5% imiquimod cream three times per week for six weeks. Cinnamomum cassia was given orally, five days per week, at 200 mg/kg. Results: Concomitant to TLR7-MYD88 pathway activation, the p-NRF2/NRF2 and p-FOXO3/FOXO3 ratios were increased in the hippocampus and alleviated by cinnamon treatment. BCL-2 positivity was enhanced in hippocampal neurons and reversed only by preventive cinnamon administration. In vitro, exposure of hippocampal cells to the plasma of different groups induced a surge in oxidative stress. This was associated with an increased t-BID/BID ratio. Cinnamon treatment, particularly in the preventive arm, normalized these modifications. Conclusions: Our study shows a neuroprotective effect of cinnamon by rescuing brain redox and apoptosis homeostasis in lupus, paving the way for its use as a natural therapeutic compound in the clinical management of lupus. [ABSTRACT FROM AUTHOR]

Antimalarials (AMs), particularly hydroxychloroquine (HCQ) and chloroquine (CQ), are the cornerstone of the treatment for both systemic lupus erythematosus (SLE) and cutaneous lupus erythematosus (CLE). HCQ and CQ are recommended as first‐line oral agents in all CLE guidelines. Initially thought to have potential therapeutic effects against COVID‐19, HCQ has drawn significant attention in recent years, highlighting concerns over its potential toxicity among patients and physicians. This review aims to consolidate current evidence on the efficacy of AMs in CLE. Our focus will be on optimizing therapeutic strategies, such as switching from HCQ to CQ, adding quinacrine to either HCQ or CQ, or adjusting HCQ dose based on blood concentration. Additionally, we will explore the potential for HCQ dose reduction or discontinuation in cases of CLE or SLE remission. Our review will focus on the existing evidence regarding adverse events linked to AM usage, with a specific emphasis on severe events and those of particular interest to dermatologists. Last, we will discuss the optimal HCQ dose and the balance between preventing CLE or SLE flares and minimizing toxicity. [ABSTRACT FROM AUTHOR]

Autoimmunity is characterized by loss of tolerance to tissue-specific as well as systemic antigens, resulting in complex autoantibody landscapes. Here, we introduce and extensively validate the performance characteristics of a murine proteome-wide library for phage display immunoprecipitation and sequencing (PhIP-seq) in profiling mouse autoantibodies. This library was validated using 7 genetically distinct mouse lines across a spectrum of autoreactivity. Mice deficient in antibody production (Rag2-/- and μMT) were used to model nonspecific peptide enrichments, while cross-reactivity was evaluated using anti-ovalbumin B cell receptor-restricted OB1 mice as a proof of principle. The PhIP-seq approach was then utilized to interrogate 3 distinct autoimmune disease models. First, serum from Lyn-/- IgD+/- mice with lupus-like disease was used to identify nuclear and apoptotic bleb reactivities. Second, serum from nonobese diabetic (NOD) mice, a polygenic model of pancreas-specific autoimmunity, was enriched in peptides derived from both insulin and predicted pancreatic proteins. Lastly, Aire-/- mouse sera were used to identify numerous autoantigens, many of which were also observed in previous studies of humans with autoimmune polyendocrinopathy syndrome type 1 carrying recessive mutations in AIRE. These experiments support the use of murine proteome-wide PhIP-seq for antigenic profiling and autoantibody discovery, which may be employed to study a range of immune perturbations in mouse models of autoimmunity profiling.

BackgroundSystemic lupus erythematosus (SLE) patients are prone to frequent emergency department (ED) visits. This study explores the epidemiology and outcomes of ED visits by patients with SLE utilizing the Nationwide Emergency Department Sample (NEDS).MethodsUsing NEDS (2019), SLE ED visits identified using ICD-10 codes (M32. xx) were compared with non-SLE ED visits in terms of demographic and clinical features and primary diagnoses associated with the ED visits. Factors associated with inpatient admission were analyzed using logistic regression. Variations in ED visits by age and race were assessed.ResultsWe identified 414,139 (0.35%) ED visits for adults ≥ 18 years with SLE. ED visits with SLE comprised more women, Black patients, ages 31-50 years, Medicare as the primary payer, and had higher comorbidity burden. A greater proportion of Black and Hispanic SLE patients who visited the ED were in the youngest age category of 18-30 years (around 20%) compared to White patients (less than 10%). Non-White patients had higher Medicaid utilization (27%-32% vs 19% in White patients). Comorbidity patterns varied based on race, with more White patients having higher rates of hyperlipidemia and ischemic heart disease (IHD) and more Black patients having chronic kidney disease (CKD), hypertension, and heart failure. Categorizing by race, SLE/connective tissue disease (CTD) and infection were the most prevalent primary ED diagnosis in non-White and White patients, respectively. Age ≥ 65 years, male sex, and comorbidities were linked to a higher risk of admission. Black race (OR 0.86, p = .01) and lowest income quartile (OR 0.78, p = .003) had lower odds of inpatient admission.ConclusionInfection and SLE/CTD were among the top diagnoses associated with ED visits and inpatient admission. Despite comprising a significant proportion of SLE ED visits, Black patients had lower odds of admission. While the higher prevalence of older age groups, hyperlipidemia, and IHD among White patients may partly explain the disparate results, and further study is needed to understand the role of other factors including reliance on the ED for routine care compared among Black patients, differences in insurance coverage, and potential socioeconomic biases among healthcare providers.

Abstract Background Rituximab (RTX) has been utilised off‐label for a variety of dermatological indications beyond pemphigus vulgaris. Efficacy has been reported in other immunobullous disorders, inflammatory dermatoses and connective tissue diseases. Objectives To assess the off‐label use of RTX in our centre with respect to indications, frequency and duration of treatment, efficacy, and adverse events. Methods Charts were retrospectively reviewed for all patients who received dermatologist‐prescribed RTX infusions off‐label at our centre between 2009 and 2022. Efficacy was categorised based on reported percentage reduction of disease activity: very good (75%–100%), good (50%–74%), partial (25%–49%) and none (0%–24%). Results Twenty‐nine patients received RTX off‐label during this time period. Infusions were discontinued in 28% (n = 8), due to insufficient clinical response. Median treatment duration for those on 6‐12‐monthly regular infusions was 2.4 years (range 0.5–11 years). Indications included cutaneous lupus (n = 9), mucous membrane pemphigoid (n = 5), pyoderma gangrenosum (n = 6), lichen planus (n = 2), dermatomyositis (n = 1), livedoid vasculitis (n = 1), sarcoidosis (n = 1), bullous pemphigoid (n = 1), pemphigus vulgaris, foliaceus and vegetans (n = 1 each). Clinical improvement was documented in 79% (n = 23); very good in 48% (n = 14), good in 17% (n = 5), and moderate in 14% (n = 4). Clinical efficacy in immunobullous disorders was 100% (9/9), 67% in cutaneous lupus (6/9), 33% in pyoderma gangrenosum (2/6), and 50% in lichen planus (1/2). No side effects were documented for 79% (n = 23). Adverse peri‐infusion events were seen in three patients (10%). Four patients died during follow up; one due to neutropenic sepsis with a background of advanced malignancy, and three due to Covid‐19. Conclusions RTX was prescribed for multiple off‐label dermatological indications, often for recalcitrant disease. Responses were good overall, with a reassuring safety profile. Three patients died of Covid‐19; knowledge of the impact of RTX on the immune response and efficacy of vaccines is expanding and will continue to inform guidelines for RTX use in the post‐Covid era.

Abstract Systemic lupus erythematosus (SLE) is a multifactorial disease characterized by the convergence of genetic, immunological, and viral elements resulting in a complex interaction of both internal and external factors. The role of the Epstein-Barr virus (EBV) and human endogenous retroviruses (HERV-E) as triggers and maintenance elements in the pathogenesis of SLE has been widely recognized. Previous studies have independently evaluated the effects of EBV and HERV-E in this disease. In this work, for the first time, these viral factors are jointly investigated in SLE patients. This study aimed at assessing the differential expression of immune regulatory genes and the incidence of specific viral pathogens (EBV and HERV-E), alongside the detailed characterization of surface markers in T- and B-lymphocytes in patients with SLE and control participants. A comparative analysis between patients with SLE and control participants was performed, evaluating the expression of phenotypic markers and genes involved in the immune response (TNF-α, IL-2, IL-6, IL-10, IFNG, TLR3), as well as HERV-E gag and EBV viral genes (LMP1 and BZLF1).A significant association between SLE and EBV was found in this study. A notable increase in EBV LMP1 gene expression was observed in patients with SLE . Also, a significant overexpression of HERV-E was observed, in addition to a considerable increase in the distribution of the cell surface marker CD27 + on T- and B-lymphocytes, observed in individuals with SLE compared to the control group. This study provides evidence regarding the role that EBV virus plays in lymphocytes in the context of SLE, highlighting how both the virus and the host gene expression may influence disease pathogenesis by altering immune regulatory pathways mediated by TNF-α, IFN-γ, and IL-10, as well as parallel overexpression of HERV-E gag. The decrease in TLR3 could indicate a compromised antiviral response, which could facilitate viral reactivation and contribute to disease activity.

Viral infections caused by exposure to viruses such as Epstein–Barr, cytomegalovirus, or Parvovirus B19 have always been considered predisposing environmental factors for the onset of autoimmune diseases. More recently, autoimmune mechanisms such as molecular mimicry, T-cell activation, transient immunosuppression and inflammation have also been observed in cases of SARS-CoV-2 infection. Several newly diagnosed autoimmune disorders have been reported post-COVID-19, such as COVID-19-associated multisystemic inflammatory syndrome in children (MIS-C), type 1 diabetes mellitus, systemic lupus erythematosus, or rheumatoid arthritis. In this article, we present a new case of paediatric systemic lupus erythematosus (SLE) with haematological (macrophage activation syndrome), renal (stage 2), cutaneous (urticarial vasculitis) and digestive involvement, onset three and a half months post-COVID-19. In the dynamics, de novo infection generated by Epstein–Barr exposure was associated. The diagnosis was confirmed based on EULAR/ACR 2019 criteria. The aim of the article is to present a possible correlation between SARS-CoV-2 and Epstein–Barr as extrinsic factors in triggering or activating paediatric systemic lupus erythematosus. Keywords: paediatric systemic lupus erythematosus; post-COVID-19; Epstein–Barr; SARS- CoV-2; case report; paediatric patient.

ObjectiveIn a study of physical and cognitive functioning among predominantly Black individuals with systemic lupus erythematosus (SLE), we compared remotely administered physical and cognitive performance assessments to those collected in person.MethodsA subset of participants who completed an in-person visit in our parent study from 2021 to 2022 (n = 30) were recruited to complete a second, remote visit within 28 days. Physical performance (measured by a modified Short Physical Performance Battery [SPPB]; range 0-12; subscale ranges 0-4; higher = better performance) and cognitive performance (episodic and working memory adjusted t-scores, measured using NIH Toolbox) were measured at both visits. Mean scores were compared using paired t-tests; intraclass correlation coefficients (ICCs) were obtained from two-way mixed effects models. Linear and logistic models were used to estimate stratified associations between performance measures and related outcomes.ResultsParticipants were primarily female (93.3%) and Black (93.3%). In-person versus remote overall SPPB (8.76 vs. 9.43) and chair stand (1.43 vs. 1.90) scores were statistically significantly lower. t-Scores for episodic memory (47.27 vs. 49.53) and working memory (45.37 vs. 47.90) were lower for in-person versus remote visits. The ICC for overall SPPB indicated good agreement (0.76), whereas the ICCs for episodic (0.49) and working memory (0.57) indicated poor-moderate agreement. Associations between assessments of performance with related outcomes were similar and did not statistically significantly differ by modality of visit.ConclusionTo possibly expand and diversify pools of participants in studies of physical and cognitive performance in SLE, remote administration of assessments should be considered for future research.

ObjectiveStudies have suggested a potential link between traumatic experiences, psychological stress, and autoimmunity, but the impact of stress on disease activity and symptom severity in systemic lupus erythematosus (SLE) remains unclear. The present study was undertaken to examine whether increases in perceived stress independently associate with worse SLE disease outcomes over 3 years of follow-up.MethodsParticipants were drawn from the California Lupus Epidemiology Study (CLUES). Stress was measured annually using the 4-item Perceived Stress Scale (PSS). Participants with increases of ≥0.5 SD in PSS score were defined as having an increase in stress. Four outcomes were measured at the year 3 follow-up visit: physician-assessed disease activity (Systemic Lupus Erythematosus Disease Activity Index); patient-reported disease activity (Systemic Lupus Activity Questionnaire); pain (Patient-Reported Outcomes Measurement Information System [PROMIS] pain interference scale); and fatigue (PROMIS fatigue scale). Multivariable linear regression evaluated longitudinal associations of increase in stress with all 4 outcomes while controlling for potential confounders.ResultsThe sample (n = 260) was 91% female, 36% Asian, 30% White, 22% Hispanic, and 11% African American; the mean ± SD age was 46 ± 14 years. In adjusted longitudinal analyses, increase in stress was independently associated with greater physician-assessed disease activity (P = 0.015), greater self-reported disease activity (P

BackgroundWe aimed to identify factors associated with a significant reduction in SLE disease activity over 12 months assessed by the BILAG Index.MethodsIn an international SLE cohort, we studied patients from their 'inception enrolment' visit. We also defined an 'active disease' cohort of patients who had active disease similar to that needed for enrolment into clinical trials. Outcomes at 12 months were; Major Clinical Response (MCR: reduction to classic BILAG C in all domains, steroid dose of ≤7.5 mg and SLEDAI ≤ 4) and 'Improvement' (reduction to ≤1B score in previously active organs; no new BILAG A/B; stable or reduced steroid dose; no increase in SLEDAI). Univariate and multivariate logistic regression with Least Absolute Shrinkage and Selection Operator (LASSO) and cross-validation in randomly split samples were used to build prediction models.Results'Inception enrolment' (n = 1492) and 'active disease' (n = 924) patients were studied. Models for MCR performed well (ROC AUC = .777 and .732 in the inception enrolment and active disease cohorts, respectively). Models for Improvement performed poorly (ROC AUC = .574 in the active disease cohort). MCR in both cohorts was associated with anti-malarial use and inversely associated with active disease at baseline (BILAG or SLEDAI) scores, BILAG haematological A/B scores, higher steroid dose and immunosuppressive use.ConclusionBaseline predictors of response in SLE can help identify patients in clinic who are less likely to respond to standard therapy. They are also important as stratification factors when designing clinical trials in order to better standardize overall usual care response rates.

ObjectivesTrauma has been linked to incident SLE, but its relationship with SLE disease activity is unknown. This analysis examines associations between trauma exposures and patient-reported SLE disease activity and flares.MethodsData were from the California Lupus Epidemiology Study (CLUES). Flares were self-reported as any flare and, of those, flares accompanied by medical care (hospitalization or physician contact). The Systemic Lupus Activity Questionnaire (SLAQ) assessed disease activity. The Brief Trauma Questionnaire (BTQ) assessed all historical trauma exposures. The Adverse Childhood Experiences (ACEs) questionnaire was available for a subset. Multivariable regression analyses (n = 252) examined whether trauma exposure was associated with flares or SLAQ controlling for age, sex, poverty, race/ethnicity, comorbidities, perceived stress, disease duration and self-reported disease damage.ResultsExcluding exposure to serious illness, 63.4% reported ≥1 trauma exposure. Any traumatic event, excluding illness, doubled the odds of a flare [OR 2.27 (95% CI 1.24, 4.17)] and was associated with significantly higher SLAQ scores [β 2.31 (0.86, 3.76)]. Adjusted odds of any flare and flare with medical care were significantly elevated for those with both BTQ and ACE exposures [5.91 (2.21, 15.82) and 4.69 (1.56, 14.07), respectively]. SLAQ scores were also higher for those with both exposures [β 5.22 (3.00, 7.44)].ConclusionIn this cohort, those with a history of trauma reported more flares and greater disease activity. Identifying mechanisms of associations between trauma and disease activity and flares, as well as interventions to mitigate the effects of trauma exposures is critical, given the high rates of trauma exposures.

Introduction Systemic Lupus Erythematosus, an autoimmune disease, can target various organs of the human body. Lupus nephritis (LN) is a major complication affecting almost half of all SLE patients, with classes “III and IV” being the most aggressive. The severity and prognosis of LN can be influenced by different biomarkers, some of which are used as therapeutic targets. One such target is the B-cell activating factor (BAFF), a key figure in the pathophysiology of SLE. New add-on treatments have emerged in the treatment of LN targeting BAFF as well as other pathways. Assortment of patients to suitable treatment combinations needs more precision using guiding markers.Methods This prospective study aims to explore BAFF-expression in patients with active-proliferative LN and its possible association with the response after induction therapy. Peripheral blood mononuclear cells (PBMC) and renal tissue samples (if applicable) were collected from participants before the initiation of induction treatment. RNA was extracted, and the expression levels of BAFF-mRNA were measured using quantitative real-time polymerase chain reaction. Clinical and laboratory data, including disease activity indices and renal functions, were recorded at baseline and 6-months after the commencement of the induction treatment.Results The study included 24 patients,14 responders and 10 non-responders. At baseline, median PBMC BAFF-mRNA expression was nearly identical in responders and non-responders. Renal BAFF-expression was found to be higher in non-responders, although non-significant (p = 0.21). Contrary to PBMC BAFF expression, renal BAFF-mRNA was negatively correlated with baseline glomerular filtration rate and with the primary endpoint of response, which was reduction of proteinuria to≥50% of baseline (p = 0.07).Conclusions Renal BAFF expression could be a better representative of severity and therapeutic response than blood expression. We acknowledge that the use of BAFF expression as a predictive for early refractoriness to therapy in LN is not yet conclusive.

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by immune system dysfunction that can lead to serious health issues and mortality. Recent investigations highlight the role of gut microbiota alterations in modulating inflammation and disease severity in SLE. This review specifically summaries the variations in gut microbiota composition across various murine models of lupus. By focusing on these differences, we aim to elucidate the intricate relationship between gut microbiota dysbiosis and the development and progression of SLE in preclinical settings. [ABSTRACT FROM AUTHOR]

Abstract Background Systemic lupus erythematosus (SLE) is a life-threatening, chronic, autoimmune disease requiring long term subspecialty care due to its complex and chronic nature. Childhood-onset SLE (cSLE) is more severe than adult-onset, and the cSLE population in South Africa has been reported to have an even higher risk than patients elsewhere. Therefore, it is critical to promptly diagnose, treat, and manage cSLE. In this paper, we aim to describe and evaluate barriers and enablers of appropriate long-term care of cSLE South Africa from the perspective of caregivers (parents or family members). Methods Caregivers (n = 22) were recruited through pediatric and adult rheumatology clinics. Individuals were eligible if they cared for youth (≤ 19 years) who were diagnosed with cSLE and satisfied at least four of the eleven ACR SLE classification criteria. Individual in-depth, semi-structured interviews were conducted between January 2014 and December 2014, and explored barriers to and facilitators of ongoing chronic care for cSLE. Data were analyzed using applied thematic analysis. Results Four barriers to chronic care engagement and retention were identified: knowledge gap, financial burdens, social stigma of SLE, and complexity of the South African medical system. Additionally, we found three facilitators: patient and caregiver education, robust support system for the caregiver, and financial support for the caregiver and patient. Conclusion These findings highlight multiple, intersecting barriers to routine longitudinal care for cSLE in South Africa and suggest there might be a group of diagnosed children who don’t receive follow-up care and are subject to loss to follow-up. cSLE requires ongoing treatment and care; thus, the different barriers may interact and compound over time with each follow-up visit. South African cSLE patients are at high risk for poor outcomes. South African care teams should work to overcome these barriers and place attention on the facilitators to improve care retention for these patients and create a model for other less resourced settings.

Abstract Objective To investigate the association between ultraviolet light index (UVI), as a marker for UV exposure, and seasonality with rash and systemic disease activity in youth with childhood-onset systemic lupus (cSLE) from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry. Methods We reviewed data on rash and disease activity from Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2 K) scores from cSLE CARRA Registry participants with visits between 2010 and 2019 and obtained zipcode level UVI data from the National Oceanic and Atmospheric Administration (NOAA). Our main exposures were UVI and season during the month of visit and one month prior to visit. We used mixed-effects logistic regression models to examine associations between regional UVI (by zipcode)/season and odds of rash and severe SLEDAI-2 K score (≥ 5 vs. 0–4), adjusting for age, sex, race and income. Results Among 1222 participants, with a mean of 2.3 visits per participant, 437 visits (15%) had rash and 860 (30%) had SLEDAI-2 K score ≥ 5. There were no associations between UVI during the month prior to visit or the month of the visit and odds of rash or elevated systemic activity. However, fall season was associated with increased odds of rash (OR = 1.59, p = 0.04), but not increased disease activity. Conclusion This study found no association between UVI and rash or UVI and disease activity. However, further studies directly measuring UV exposure and accounting for patient-level protective behavioral measures may help to better understand the complex relationship between sun exposure and SLE disease activity.

Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease that affects both men and women differently and has a variety of multisystemic symptoms. One of the diseases most often affected target organs is the skin. Different ethnic and racial groupings may display variations in disease incidence, clinical heterogeneity, and severity depending on environmental, cultural, or genetic factors. This study is conducted to determine the prevalence of SLE’s cutaneous symptoms and their relationship to organ involvement. Materials and Methods: Data were gathered for this study from the patient chart, the study design was the retrospective chart review after the consent of the patients and obtaining an ethical approval, The study was carried out in Aseer Central Hospital, Abha Saudi Arabia Results: Out of a total of 100 patients 92% were females while 8% were males. The mean (SD) of the age of the respondent was 38.3 (8.5). 89.2 of the respondents had skin manifestations Conclusion: A thorough understanding of SLE skin lesions will aid in the accurate identification of the condition and in the effective therapy of lupus patients. In order to more accurately diagnose cutaneous lesions in SLE patients, we need more dermatology and rheumatology clinics that combine expertise together.

Follicular helper T (TFH) cells mediate germinal center reactions to generate high affinity antibodies against specific pathogens, and their excessive production is associated with the pathogenesis of systemic autoimmune diseases such as systemic lupus erythematosus (SLE). ETV5, a member of the ETS transcription factor family, promotes TFH cell differentiation in mice. In this study, we examined the role of ETV5 in the pathogenesis of lupus in mice and humans. T cell-specific deletion of Etv5 alleles ameliorated TFH cell differentiation and autoimmune phenotypes in lupus mouse models. Further, we identified SPP1 as an ETV5 target that promotes TFH cell differentiation in both mice and humans. Notably, extracellular osteopontin (OPN) encoded by SPP1 enhances TFH cell differentiation by activating the CD44-AKT signaling pathway. Furthermore, ETV5 and SPP1 levels were increased in CD4+ T cells from patients with SLE and were positively correlated with disease activity. Taken together, our findings demonstrate that ETV5 is a lupus-promoting transcription factor, and secreted OPN promotes TFH cell differentiation. [ABSTRACT FROM AUTHOR]

Depressive disorders are a growing problem worldwide. They are also characterized by high comorbidity, including from the circle of dermatological diseases. Autoimmune diseases seem to be particularly correlated with depressive comorbidity, raising the question of their possible common pathomechanism. The PubMed database was searched, focusing on results published after 2016. A particular reciprocal correlation of depressive disorders with psoriasis, atopic dermatitis, alopecia areata, impetigo, lupus and systemic scleroderma was found. One possible explanation for the co-occurrence of the above diseases is that the inflammatory theory may be applicable to depression, the various elements of which also apply to autoimmune diseases. [ABSTRACT FROM AUTHOR]

Moyamoya syndrome (MMS) is a rare, chronic, progressive cerebrovascular disorder characterized by stenosis at the apices of the intracranial internal carotid arteries, including the proximal anterior cerebral arteries and middle cerebral arteries. Cerebral angiography images are used for detection through measurement. Systemic lupus erythematosus (SLE) is an autoimmune disease that can cause multisystemic involvement. The coexistence of SLE and MMS has been rarely reported in the literature. A 46-year-old male patient with malar rash, Raynaud phenomenon presented to the hospital with a complaint of weakness in the left lower extremity, which began 3 days before the date of the visit. In the diffusion magnetic resonance imaging, multiple diffusion restrictions were observed in the right frontal region. The patient underwent MR angiography, revealing stenosis in the terminal and supraclinoid segments of the right internal carotid artery, which made us consider moyamoya disease. This patient, with a malar rash and Raynaud's, a positive antibody profile, was diagnosed as a male with SLE accompanied by MMS. [ABSTRACT FROM AUTHOR]

Objectives This study aims to assess the mortality of systemic lupus erythematosus (SLE) patients and examine whether there are variations by subgroup. Methods SLE patients from 2005 to 2021 were identified from the national administrative datasets. The underlying causes of death were examined. Standardized mortality ratio (SMR) was estimated to compare the relative rate of observed deaths in SLE patients with expected deaths in the general population. The hazard ratios (HR) and 95% confidence intervals (CI) of all-cause mortality and SLE specific mortality by ethnicity were estimated after adjustment for age using a Cox proportional hazards model. Results Of the 2802 patients included for analysis, 699 (24.9%) died with 209 (29.9%) SLE deaths. The age-standardized mortality rate of SLE was 0.29 per 100 000 for women and 0.05 for men. The mean age at death was 65.3 (17.1) years. Younger patients were more likely to have SLE as the underlying cause of death, from 78.9% for those under 20 years old to 18.7% for those aged 70–79 years. Compared with the general population, SLE patients were four times more likely to die (SMR: 4.0; 95% CI: 3.7, 4.3). Young patients had higher SMRs than older patients. Māori had worse all-cause mortality (HR: 1.72; 95% CI: 1.10, 2.67) and SLE specific mortality (HR: 2.60; 95% CI: 1.29, 5.24) than others. Conclusions The outcomes of SLE in New Zealand were still very poor compared with the general population. Māori with SLE had worse survival than others. Further research is needed to identify the reasons for this disparity. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is an autoimmune disease affecting mostly women of child-bearing age. Immune dysfunction in SLE results from disrupted apoptosis which lead to an unregulated interferon (IFN) stimulation and the production of autoantibodies, leading to immune complex formation, complement activation, and organ damage. Lupus nephritis (LN) is a common and severe complication of SLE, impacting approximately 30% to 40% of SLE patients. Recent studies have demonstrated an alteration in mitochondrial homeostasis in SLE patients. Mitochondrial dysfunction contributes significantly to SLE pathogenesis by enhancing type 1 IFN production through various pathways involving neutrophils, platelets, and T cells. Defective mitophagy, the process of clearing damaged mitochondria, exacerbates this cycle, leading to increased immune dysregulation. In this review, we aim to detail the physiopathological link between mitochondrial dysfunction and disease activity in SLE. Additionally, we will explore the potential role of mitochondria as biomarkers and therapeutic targets in SLE, with a specific focus on LN. In LN, mitochondrial abnormalities are observed in renal cells, correlating with disease progression and renal fibrosis. Studies exploring cell-free mitochondrial DNA as a biomarker in SLE and LN have shown promising but preliminary results, necessitating further validation and standardization. Therapeutically targeting mitochondrial dysfunction in SLE, using drugs like metformin or mTOR inhibitors, shows potential in modulating immune responses and improving clinical outcomes. The interplay between mitochondria, immune dysregulation, and renal involvement in SLE and LN underscores the need for comprehensive research and innovative therapeutic strategies. Understanding mitochondrial dynamics and their impact on immune responses offers promising avenues for developing personalized treatments and non-invasive biomarkers, ultimately improving outcomes for LN patients. [ABSTRACT FROM AUTHOR]

The development of autoimmune diseases often takes years before clinical symptoms become detectable. We propose a mathematical model for the immune response during the initial stage of Systemic Lupus Erythematosus which models the process of aberrant apoptosis and activation of macrophages and neutrophils. NETosis is a type of cell death characterised by the release of neutrophil extracellular traps, or NETs, containing material from the neutrophil’s nucleus, in response to a pathogenic stimulus. This process is hypothesised to contribute to the development of autoimmunogenicity in SLE. The aim of this work is to study how NETosis contributes to the establishment of persistent autoantigen production by analysing the steady states and the asymptotic dynamics of the model by numerical experiment. [ABSTRACT FROM AUTHOR]

Protein kinase C delta (PKCδ) has emerged as a key protective molecule against systemic lupus erythematosus (SLE or lupus), an autoimmune disease characterized by anti-double stranded (ds) DNA IgGs. Although PKCδ-deficient mice and lupus patients with mutated PRKCD genes clearly demonstrate the requirement for PKCδ in preventing lupus autoimmunity, this critical tolerance mechanism remains poorly understood. We recently reported that PKCδ acts as a key regulator of B cell tolerance by selectively deleting anti-dsDNA B cells in the germinal center (GC). PKCδ's tolerance function is activated by sphingomyelin synthase 2 (SMS2), a lipid enzyme whose expression is generally reduced in B cells from lupus patients. Moreover, pharmacologic strengthening of the SMS2/PKCδ tolerance pathway alleviated lupus pathogenesis in mice. Here, we review relevant publications in order to provide mechanistic insights into PKCδ's tolerance activity and discuss the potential significance of therapeutically targeting PKCδ's tolerance activity in the GC for selectively inhibiting lupus autoimmunity. [ABSTRACT FROM AUTHOR]