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OBJECTIVES: ANA-associated RMDs (ANA-RMDs-SLE, pSS, scleroderma, inflammatory myositis, mixed connective tissue disease (MCTD) and undifferentiated connective tissue disease) are a disease spectrum with overlapping clinical and immunological features. Musculoskeletal inflammation is common and impactful across ANA-RMDs. We evaluated musculoskeletal inflammation (ANA-arthritis) prevalence in a multi-disease ANA-RMD study, assessed its clinical impact across ANA-RMD diagnoses, proposed new basket groupings of patients and evaluated immunological profiles in legacy and new basket contexts. METHODS: An observational study enrolled ANA-RMD patients. Demographic variables, comorbidities, therapies, disease activity instruments (BILAG, SLEDAI, ESSDAI, physician-VAS), patient-reported outcomes (SF36, FACIT-Fatigue, EQ5D, ICECAP-A, WPAI, patient-VAS) and biomarker profile (6 gene expression scores, flow cytometry, autoantibody profile) were analysed. Reclustering utilized Gaussian Mixture Modelling (GMM). Clinical and immune features of new and legacy clusters were compared. RESULTS: Inflammatory MSK symptoms were prevalent across ANA-RMDs, in 213/294 patients. In ANA-arthritis patients, most variables did not differ between diagnoses, excluding EQ5D-5L index and mobility domains (lower in MCTD/pSS, both p< 0.05). Fibromyalgia and osteoarthritis prevalence were similar across diagnoses. Therapy use differed significantly, biologic use being greatest in SLE (p< 0.05).GMM yielded two multi-disease clusters; High-MSK disease activity (n = 89) and Low-MSK disease activity (n = 124). High-MSK disease activity contained all patients with active joint swelling and had significantly higher prednisolone usage, PGA and Sm/RNP/SmRNP/Chromatin positivity, Tetherin-MFI and Interferon Score-A activity; with numerically lower fibromyalgia and osteoarthritis prevalence. CONCLUSION: We define ANA-Arthritis, a more clinically and immunologically homogeneous population than existing RMDs for trials, and a more prevalent population for therapies in the clinic.
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BACKGROUND: Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease characterized by immune mechanisms dysregulation, leading to the production of diverse autoantibodies. However, the immune pathways underlying B-cell function and phenotypic abnormalities related to SLE pathogenesis remain incompletely understood. OBJECTIVE: To explore new markers of SLE activity and potential targets for SLE immunotherapy. METHODS: Collect peripheral blood mononuclear cells (PBMCs) from SLE patients and healthy controls (HC). Use flow cytometry to detect CD39 and CD73 expression on B cell subsets and enzyme-linked immunosorbent assay (ELISA) to measure adenosine (ADO) concentrations in SLE patients' serum. Compare CD39+CD73+ B cell subsets frequency and ADO concentrations in SLE patients and HC group. Additionally, analyze the correlation between CD39+CD73+ B cell subsets frequency and clinical laboratory parameters. RESULTS: CD39 and CD73 are simultaneously highly expressed on CD19+ B cell subsets, with significantly lower frequency of CD39+CD73+ B cell subsets in SLE patients compared to HC group. This frequency negatively correlates with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), C-reactive protein (CRP), and anti-double-stranded DNA (anti-dsDNA) antibodies, while positively correlating with IgM and prothrombin time (PT). Additionally, the frequency of CD39+CD73+ B cell subsets is significantly negatively correlated with IL-6 and IFN-α. In vitro cell experiments demonstrate that adenosine significantly inhibits R848-induced inflammatory cytokine production in a dose-dependent manner. CONCLUSION: The frequency of CD39+CD73+ B cell subsets of SLE patients is decreased, correlating with clinical laboratory parameters and disease activity. Simultaneously, ADO concentration in the patients' serum is reduced. The CD39+CD73+ B cell/ADO pathway may represent a novel immunotherapy strategy for SLE.
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OBJECTIVE: Skin involvement is common in systemic lupus erythematosus (SLE), but may be resistant to conventional treatment. We sought to evaluate the efficacy of anifrolumab (ANI) in refractory cutaneous manifestations of SLE. METHODS: Case series of patients with refractory cutaneous SLE from three Rheumatology Departments in Greece. Outcome measures were improvement in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), physician global assessment (PGA) and Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI). Clinically relevant improvement in skin was defined as decrease ≥50% (CLASI50) from baseline values. RESULTS: Eighteen patients received ANI; all had active skin involvement at baseline. Mean (SD) SLEDAI and PGA at ANI initiation were 7.4 (2.7) and 1.4 (0.5), respectively, with a mean prednisone dose 4.9 (4.5) mg/day. Mean CLASI (Activity/Damage) at baseline was 13.9 (9.7)/2.9 (4.6). Patients were refractory to a mean 6.3 (1.5) immunomodulatory agents (including hydroxychloroquine and glucocorticoids) before the initiation of ANI. After a mean 8.5 (4.6) months, 89% (n = 16/18) of patients demonstrated significant improvement in general lupus and cutaneous disease activity, and glucocorticoid tapering. Mean SLEDAI and mean CLASI at last visit were 3.4 (1.9) and 2.1 (2.4)/1.4 (2.2), respectively, and mean daily prednisone dose decreased to 2.4 (2.2). Of note, in this group of highly refractory patients CLASI50 was achieved in 16/18 (89%) patients. One patient discontinued ANI after 4 infusions due to a varicella-zoster virus infection and one patient, who initially responded to treatment with ANI, experienced a skin flare due to temporary discontinuation due to Covid 19 infection. DORIS remission and LLDAS were attained in two (11.1%) and eleven (61.1%) patients, respectively. CONCLUSION: Anifrolumab is highly effective in various skin manifestations of SLE, even after prior failure to multiple treatments.
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Introduction: Several studies have reported associations between various autoimmune diseases and migraine. Using Mendelian randomization (MR), this study aimed to evaluate the interplay between autoimmune diseases and migraine. Methods: Here, instrumental variables, exposure factors, and outcome factors for 10 common autoimmune diseases and migraine and its subtypes were screened. This screening utilized comprehensive statistics from Europe's largest genome-wide association study and performed reverse MR analysis on positive results. The causality between autoimmune diseases and migraine was comprehensively assessed using multiple analytical methods. Additionally, sensitivity analyses, such as the horizontal diversity heterogeneity and leave-one-out method, were performed. Results: Random-effects inverse variance weighting analysis revealed a causal correlation between autoimmune hyperthyroidism and migraine (p = 0.0002), and this association was consistent across both migraine with aura (MA; p = 0.006) and migraine without aura (MO; p = 0.017). In addition, there was a positive causal association between systemic lupus erythematosus (SLE) and MA (p = 0.001) and between hypothyroidism and MO (p = 0.038). There is insufficient evidence to substantiate a causal link between outcomes and other autoimmune-related disorders, and reverse MR results did not reveal a causal relationship between migraines and these autoimmune disorders. The validity of the results was demonstrated by a sensitivity analysis; horizontal pleiotropy and heterogeneity were not observed. Discussion: This study observed a positive genetic association between autoimmune hyperthyroidism and migraines. In addition, SLE positively affects MA, and hypothyroidism contributes to the incidence of MO. These results have great significance for future research and prevention of migraine.
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BACKGROUND: The interferon-gamma (IFN-γ) release assay (IGRA) is an important laboratory diagnosis for latent Mycobacterium tuberculosis (TB) infection. The TB-IGRA measures the release of IFN-γ from peripheral blood cells, who are exposed to TB antigen (Ag), mitogen (MT), or negative/nil control (NL) in vitro. While, an exceptional higher TB Ag-NL level will reflect an elevation of peripheral lymphocytes released IFN-γ in a same condition. Therefore, we found that the elevated levels of TB Ag-NL could become a new biomarker for the diagnosis and treatment of pediatric systemic lupus erythematosus (SLE) patients. METHODS: We have analyzed the clinical data of 776 children who are underwent TB-IGRA testing in the Department of Allergy and Rheumatology of Guangzhou Women and Children's Medical Center from 2018 to 2020. To investigate the association between TB Ag-NL and SLE, we have analyzed the clinical data of 47 SLE patients and TB Ag-NL testing results, and then evaluated the association between TB Ag-NL and SLE disease activity. RESULTS: The TB Ag-NL levels were significantly higher in patients with active SLE than those in inactive SLE (p = 0.0002). The TB Ag-NL levels were positively correlated with the SLE disease activity index (SLEDAI) and laboratory diagnosis parameters. The mean value of TB Ag-NL in SLE patients (0.04191 ± 0.07955, IU/mL) were significantly higher than those in patients with juvenile dermatomyositis (JDM) (0.0158 ± 0.0337, IU/mL, p = 0.036), juvenile idiopathic arthritis (JIA) (0.0162 ± 0.0388, IU/mL, p = 0.001), and healthy controls (HC) (0.0001 ± 0.0027, IU/mL, p = 0.0003). Therefore, the elevated TB Ag-NL levels could serve as a potential diagnostic biomarker of SLE, especially for the active SLE. CONCLUSION: The detection of IFN-γ release levels by the TB-IGRA may be useful to assess SLE disease activity in pediatric patients with active SLE.
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Biomarcadores , Ensayos de Liberación de Interferón gamma , Lupus Eritematoso Sistémico , Humanos , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/sangre , Femenino , Niño , Masculino , Biomarcadores/sangre , Ensayos de Liberación de Interferón gamma/métodos , Adolescente , Interferón gamma/sangre , Tuberculosis Latente/diagnóstico , Antígenos Bacterianos/inmunología , PreescolarRESUMEN
The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway has been identified as a significant modulator of inflammation in various clinical contexts, including infection, cellular stress, and tissue injury. The extensive participation of the cGAS-STING pathway can be attributed to its ability to detect and control the cellular reaction to DNAs originating from both microorganisms and hosts. These DNAs are well recognized as molecules linked with potential risks. At physiological levels, the STING signaling system exhibits protective effects. However, prolonged stimulation of this pathway contributes to autoimmune disorder pathogenesis. The present paper provides an overview of the activation mechanism of the cGAS-STING signaling pathways and their associated significant functions, as well as therapeutic interventions in the context of systemic lupus erythematosus (SLE). The primary objective is to enhance our comprehension of SLE and facilitate more effective diagnosis and treatment strategies for this condition.
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BACKGROUND: Monogenic lupus is a rare variant of systemic lupus erythematosus (SLE) that develops in patients with a single gene disorder. Early complement component deficiencies were the first forms of monogenic lupus to be described and C1Q gene mutations are one of the most common forms. C1QA complement deficiency has been reported to occur usually due to biallelic variants in C1QA gene and compound heterozygous variants in C1QA gene have rarely been reported. Majority of the monogenic lupus patients with C1Q deficiency present with mucocutaneous, renal, and musculoskeletal manifestations. Our patient is an unusual case of monogenic lupus with severe neurological manifestations along with cutaneous, haematological, and hepatic manifestations secondary to rare compound heterozygous variants in C1QA gene and anti-ribosomal P autoantibody positivity. She was treated with glucocorticoids, rituximab and fresh frozen plasma with partial neurological recovery. Thus, we present a unique case of monogenic lupus due to a rare compound heterozygous variant in C1QA gene with a brief review of literature.
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OBJECTIVE: To improve our understanding of systemic lupus erythematosus (SLE)-macrophage activation syndrome (MAS). METHODS: A systematic review was performed, to retrieve all those papers on patients with SLE-MAS, in individual or aggregated form. The data in each of these medical records were extracted and analyzed to identify the characteristics of SLE-MAS. RESULTS: A total of 86 SLE-MAS patients were included (25 males and 61 females. The mean (±standard error of the mean) age was 31.21 ± 1.694 years. MAS occurred as the initial presentation of SLE in 47 people (54.65%) and during the course of SLE in 39 (45.35%). A coinfection was reported in 23 (26.74%) patients. The mean Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score was 16.54 ± 0.9462. Overall, 10 patients (11.63%) died. The SLEDAI-2K score was higher in patients with MAS as an initial manifestation of SLE than in those where MAS occurred during the course of SLE. The proportion of patients receiving steroid pulse therapy was lower in patients with coinfections. The deceased group demonstrated lower platelet and ferritin levels. Multiple regression analysis revealed that age and thrombocytopenia were independent factors associated with poor prognosis. In receiver operating characteristic analysis, a platelet count cutoff value of ≤47 × 109/L was a predictor of poor outcome. CONCLUSIONS: SLE-MAS patients demonstrated high lupus activity, and lupus activity was especially higher in patients with MAS as an initial manifestation. Lupus activity was the predominant trigger of lupus MAS. Thrombocytopenia was an independent factor for poor prognosis.
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Lupus Eritematoso Sistémico , Síndrome de Activación Macrofágica , Humanos , Síndrome de Activación Macrofágica/diagnóstico , Síndrome de Activación Macrofágica/etiología , Síndrome de Activación Macrofágica/sangre , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/inmunología , Femenino , Masculino , Adulto , Trombocitopenia/etiología , Trombocitopenia/sangre , Pronóstico , Índice de Severidad de la EnfermedadRESUMEN
Systemic lupus erythematosus (SLE) is the prototype of autoimmune diseases and can manifest with a plethora of clinical signs and symptoms associated with a myriad of laboratory abnormalities. An infrequent but potentially lethal complication of SLE is macrophage activation syndrome (MAS). The diagnosis of MAS in SLE can be very challenging due to similarities in presentation of both flares and infections, such as fever, lymphadenopathy, splenomegaly, and cytopenias. These aggravating factors contribute to the increased risk of poor outcomes in SLE-associated MAS. Indeed, at the moment MAS remains invariably lethal if untreated and still has a high mortality rate with treatment. In this chapter, we discuss several aspects of MAS in the context of SLE and in particular, the pathogenesis of MAS in SLE, how MAS presents in pediatric versus adult SLE, and, finally, MAS treatment in SLE and future directions.
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Lupus Eritematoso Sistémico , Síndrome de Activación Macrofágica , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/complicaciones , Humanos , Síndrome de Activación Macrofágica/diagnóstico , Síndrome de Activación Macrofágica/etiología , Síndrome de Liberación de Citoquinas/inmunología , Síndrome de Liberación de Citoquinas/etiología , Citocinas/metabolismoRESUMEN
Systemic lupus erythematosus (SLE) is a chronic autoimmune condition that can affect multiple organ systems and is heterogenous in its presentation and response to therapy. When diagnosed in childhood, SLE is associated with increased morbidity and mortality compared to adult SLE, often requiring substantial immunosuppression with the risk of significant side effects. There remains a significant unmet need for new therapies that can improve disease control and reduce glucocorticoid and other toxic medication exposure for patients with severe or refractory disease. The pathogenesis of SLE involves B cell dysregulation and autoantibody production, which are a hallmark of the disease. Currently approved B cell directed therapies often result in incomplete B cell depletion and may not target long-lived plasma cells responsible for SLE autoantibodies. It is hypothesized that by persistently eliminating both B cells and plasmablasts, CAR T therapy can halt autoimmunity and prevent organ damage in patient's refractory to current B cell-depleting treatments. Herein we summarize the current preclinical and clinical data utilizing CAR T cells for SLE and discuss the future of this treatment modality for lupus.
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Inmunoterapia Adoptiva , Lupus Eritematoso Sistémico , Humanos , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/terapia , Niño , Inmunoterapia Adoptiva/métodos , Inmunoterapia Adoptiva/efectos adversos , Linfocitos B/inmunología , Linfocitos T/inmunología , Receptores Quiméricos de Antígenos/inmunologíaRESUMEN
Systemic autoimmune diseases are complex conditions characterized by an immune system dysregulation and an aberrant activation against self-antigens, leading to tissue and organ damage. Even though genetic predisposition plays a role, it cannot fully explain the onset of these diseases, highlighting the significant impact of non-heritable influences such as environment, hormones and infections. The exposome represents all those factors, ranging from chemical pollutants and dietary components to psychological stressors and infectious agents. Epigenetics, which studies changes in gene expression without altering the DNA sequence, is a crucial link between exposome and the development of autoimmune diseases. Key epigenetic mechanisms include DNA methylation, histone modifications, and non-coding RNAs. These epigenetic modifications could provide a potential piece of the puzzle in understanding systemic autoimmune diseases and their connection with the exposome. In this work we have collected the most important and recent evidence in epigenetic changes linked to systemic autoimmune diseases (systemic lupus erythematosus, idiopathic inflammatory myopathies, ANCA-associated vasculitis, and rheumatoid arthritis), emphasizing the roles these changes may play in disease pathogenesis, their potential as diagnostic biomarkers and their prospective in the development of targeted therapies.
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We present the case of a 39-year-old woman who was diagnosed with SLE and antiphospholipid antibodies 8 years ago. The chief manifestations of her disease included low-grade fever and polyarthritis. Eight months before presentation, she experienced symptoms attributed to a flare of SLE, leading to an increase in immunomodulatory treatment with no improvement. She presented to the emergency room with acute onset of dyspnea. Clubbing of her fingers and toes was noted. When questioned, she reported the onset of clubbing 5 months earlier. A CTA was performed to rule out pulmonary embolism, which was excluded, although it revealed a severely damaged mitral valve with severe insufficiency and a large mass on the valve, protruding into the left atrium. Antibiotics were started, with a working diagnosis of infectious endocarditis; however, the severe mitral valve dysfunction lead to emergency mitral valve replacement, revealing an organized thrombus. She was treated with anticoagulation, with a working diagnosis of Libman-Sacks endocarditis, with no improvement. Additional immunosuppression failed to improve her symptoms. Enlargement of the thrombotic mass and an increased gradient across the prosthetic mitral valve led to repeat surgery, culminating in a diagnosis of high-grade sarcoma within the left atrial mass. We further discuss cardiac sarcoma and describe the occurrence of clubbing in patients with sarcoma. This case highlights the importance of interdisciplinary collaboration and the need for vigilant monitoring in refractory cases, particularly when atypical presentations arise.
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High mobility group box proterin-1 (HMGB-1) is a multifunctional protein that can be released by various programmed cell deaths (PCDs), such as necroptosis and ferroptosis. PCDs play a critical role in the pathogenesis of systemic lupus erythematosus (SLE). However, the role of HMGB-1 in the process of SLE remains unclear. This study aims to demonstrate the potential diagnosing role of serum HMGB-1 in SLE that released by necroptosis and ferroptosis. We found that the serum levels of HMGB-1, receptor-interacting protein kinase 3 (RIPK3) /mixed lineage kinase domain-like protein (MLKL) related with necroptosis, and metabolites associated with ferroptosis were significantly upregulated in SLE patients compared to HC individuals. These serum levels were positively correlated with SLE disease activity. Additionally, the serum level of HMGB-1 showed a strong positive correlated with the levels of RIPK3/MLKL and ferroptosis metabolites. Moreover, the serum level of HMGB-1 was correlated with renal involvement and high-antinuclear antibodies (ANA) titer. After SLE serum and interferon γ (IFN-γ) treatment in vitro, the level of necroptosis and ferroptosis markers were activated and HMGB1 was released both in HEK293 and HK2 cells. Clinically, HMGB-1 was considered as a significant independent risk factor in SLE serum by binary logistic assay. Notably, HMGB-1 exhibited outstanding diagnostic ability for SLE by the area under the curve (AUC) in receiver operating characteristic (ROC) curve analysis. Taken together, our study indicates that the serum level of HMGB-1 is a promising biomarker for the diagnosis and monitoring of SLE.
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N6-methyladenosine (m6A) modification is the most widespread RNA internal modification involved in RNA metabolism. M6A regulators consist of writers, erasers and readers. They exert their function by methylation, demethylation and recognization respectively, participating in cell biology and immune responses. Previously, the focus of m6A modification is its effect on tumor progress. Currently, extensive m6A-related studies have been performed in autoimmune diseases, such as RA, IBD and SLE, revealing that the unique influence of m6A modification in autoimmunity is undeniable. In this review, we summarize the function of m6A regulators, analyze their roles in pathogenic immune cells, summarize the m6A modification in SLE, and provide the potential m6A-targeting therapies for autoimmune diseases.
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Systemic lupus erythematosus (SLE) can adversely affect surgical outcomes, and the impact on revision total knee arthroplasty (TKA) outcomes is unclear. This study aimed to explore the impact of SLE on in-patient outcomes of revision TKA. The Nationwide Inpatient Sample (NIS) database from 2005 to 2018 was searched for patients aged ≥ 18 years old who received revision TKA. Patients with and without SLE were propensity score matched (PSM) at a 1:4 ratio. Associations between SLE and in-hospital outcomes were examined using regression analyses. The study included 133,054 patients, with 794 having SLE. After 1:4 PSM, data of 3,970 patients were analyzed (SLE, 794; non-SLE, 3,176). Multivariate-adjusted analyses revealed that SLE patients had a significantly higher risk of postoperative complications (adjusted odds ratio [aOR] = 1.23, 95% confidence interval [CI]: 1.05-1.44, p = 0.011), non-routine discharge (aOR = 1.22, 95% CI: 1.02-1.46, p = 0.028), major blood loss (aOR = 1.19), respiratory failure/mechanical ventilation (aOR = 1.79), acute kidney injury (AKI) (aOR = 1.47), and wound dehiscence (aOR = 2.09). SLE patients also had a longer length of hospital stay (aBeta = 0.31) and greater total hospital costs (aBeta = 6.35) compared to non-SLE patients. Among those with aseptic failure, SLE patients had a significantly higher risk of postoperative complications (aOR = 1.23) and non-routine discharge (aOR = 1.36). SLE is independently associated with worse in-hospital outcomes in patients undergoing revision TKA. This study highlights the importance of heightened vigilance and tailored perioperative management for patients undergoing major surgeries in the background of SLE. Key Points ⢠SLE significantly increases the risk of non-routine discharge, major blood loss, respiratory failure, acute kidney injury, and wound dehiscence, in patients undergoing aseptic and septic revision TKA. ⢠Patients with SLE experience longer hospital stays and higher hospital costs compared to those without SLE. ⢠The study's findings highlight the necessity for healthcare providers to consider the presence of SLE as a critical factor in preoperative planning and postoperative care to improve outcomes in revision TKA patients.
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Introduction This study aims to identify the influence of social determinants of health (SDoH) on patients with systemic lupus erythematosus (SLE), emphasizing racial and ethnic disparities in healthcare. Methods A cross-sectional study used the National Institute of Health's (NIH) All of Us Research Program (AoU). From 727,000 patients, SLE patients were categorized by race, ethnicity, and responses to the Social Determinants of Health survey from May 2018 until March 2023. Survey questions addressed transportation access, neighborhood safety, provider biases, and food insecurity. JMP Pro 16.0 and R 4.2.2 were used for statistical analysis. Results Significant racial disparities were evident amongst SLE patients for transportation access, neighborhood safety, food security, and respect from healthcare providers (p-value < 0.001). African Americans, Asians, and White participants showed different perceptions regarding neighborhood crime, healthcare provider courtesy, and feeling unheard by providers, with respective p-values of 0.001, 0.010, and 0.023. Hispanic participants perceived higher neighborhood crime rates, felt unsafe during nighttime walks, felt unheard by healthcare providers, and reported worrying about food security compared to non-Hispanic participants, with respective p-values of 0.003, 0.003, 0.009, and <0.001. Discussion SLE is affected by access to care, treatments, stress, and lifestyle habits. Therefore, identifying SDoH for SLE patients is critical as it impacts disease progression, leading to delays in diagnosis, improper management, and worsening morbidity. Conclusion Targeted social and community-based interventions may improve access to care, identify implicit biases among providers, and alleviate food insecurity.
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Introduction: This study explores the issue of paper-and-pencil screening tests for bipolar disorder, often leading to false positives. It discusses hypotheses that connect MDQ positivity with sleep disorders, a decline in health-related quality of life, and the impact of the COVID-19 pandemic on mood disorders. The study proposes that MDQ identifies a "Dysregulation of Mood, Energy, and Social Rhythms Syndrome" (DYMERS), indicating a stress-related condition. It aims to investigate the association between MDQ positivity and systemic lupus erythematosus (SLE) in comparison to other chronic disorders. Methods: This case-control study, conducted from April 2019 to February 2020, investigated MDQ positivity in patients with SLE. Ethical approvals were obtained, and statistical analysis was used for data assessment. Results: This is a case-controlled study where MDQ positivity was significantly higher in systemic lupus erythematosus cases than controls. The analysis compared gender, age, and the presence of depressive episodes between MDQ-positive and MDQ-negative cases, revealing some differences but no significant variations. Interestingly, no association with high prednisone or biologics use was observed. The frequency of MDQ positivity in systemic lupus erythematosus was compared to other chronic pathologies, revealing varying associations with each condition. Conclusion: This study reveals a high rate of (MDQ) positivity in systemic lupus erythematosus (SLE), associated with the risk of bipolar disorder in SLE. Notable discrepancies in MDQ positivity risk factors between SLE and bipolar disorder are observed. The study emphasizes the ability of MDQ to identify a distinct syndrome characterized by rhythm dysregulation, posing a risk for bipolar disorder and other disorders.
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Background: Factor H (FH) is a major soluble inhibitor of the complement system and part of a family comprising five related proteins (FHRs 1-5). Deficiency of FHR1 was described to be linked to an elevated risk of systemic lupus erythematosus (SLE). As FHR1 can partially antagonize the functionality of FH, an altered FHR1/FH ratio could not only enhance SLE vulnerability but also affect the disease expression. This study focuses on the analysis of FH and FHR1 at a protein level, and the occurrence of anti-FH autoantibodies (anti-FH) in a large cohort of SLE patients to explore their association with disease activity and/or expression. Methods: We assessed FH and FHR1 levels in plasma from 378 SLE patients compared to 84 healthy controls (normal human plasma, NHP), and sera from another cohort of 84 healthy individuals (normal human serum, NHS), using RayBio® CFH and CFHR1 ELISA kits. Patients were recruited by the Swiss SLE Cohort Study (SSCS). Unmeasurable FHR1 levels were all confirmed by Western blot, and in a subgroup of patients by PCR. Anti-FH were measured in SLE patients with non-detectable FHR1 levels and matched control patients using Abnova's CFH IgG ELISA kit. Results: Overall, FH and FHR1 levels were significantly higher in healthy controls, but there was no significant difference in FHR1/FH ratios between SLE patients and NHPs. However, SLE patients showed a significantly higher prevalence of undetectable FHR1 compared to all healthy controls (35/378 SLE patients versus 6/168 healthy controls; p= 0.0214, OR=2.751, 95% CI = 1.115 - 8.164), with a consistent trend across all ethnic subgroups. Levels of FH and FHR1, FHR1/FH ratios and absence of FHR1 were not consistently associated with disease activity and/or specific disease manifestations, but absence of FHR1 (primarily equivalent to CFHR1 deficiency) was linked to the presence of anti-FH in SLE patients (p=0.039). Conclusions: Deficiency of FHR1 is associated with a markedly elevated risk of developing SLE. A small proportion of FHR1-deficient SLE patients was found to have autoantibodies against FH but did not show clinical signs of microangiopathy.
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Autoanticuerpos , Factor H de Complemento , Lupus Eritematoso Sistémico , Humanos , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/sangre , Femenino , Masculino , Factor H de Complemento/metabolismo , Factor H de Complemento/inmunología , Adulto , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Persona de Mediana Edad , Proteínas Inactivadoras del Complemento C3b/genética , Adulto Joven , Anciano , Estudios de Casos y Controles , Adolescente , Proteínas SanguíneasRESUMEN
Electronic Health Records (EHRs) contain a wealth of unstructured patient data, making it challenging for physicians to do informed decisions. In this paper, we introduce a Natural Language Processing (NLP) approach for the extraction of therapies, diagnosis, and symptoms from ambulatory EHRs of patients with chronic Lupus disease. We aim to demonstrate the effort of a comprehensive pipeline where a rule-based system is combined with text segmentation, transformer-based topic analysis and clinical ontology, in order to enhance text preprocessing and automate rules' identification. Our approach is applied on a sub-cohort of 56 patients, with a total of 750 EHRs written in Italian language, achieving an Accuracy and an F-score over 97% and 90% respectively, in the three extracted domains. This work has the potential to be integrated with EHR systems to automate information extraction, minimizing the human intervention, and providing personalized digital solutions in the chronic Lupus disease domain.