Cytokine profiles and their correlation with clinical and blood parameters in rheumatoid arthritis and systemic lupus erythematosus.

The abnormal biological activity of cytokines and their imbalance are implicated in developing rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Cytokine levels were measured in RA and SLE patients and compared to healthy controls using the Wilcoxon rank sum test and Kruskal-Wallis test. The relationship between cytokine levels and blood and clinical parameters was assessed using Spearman's correlation test. Compared to healthy controls, both RA and SLE patients exhibited elevated levels of GM-CSF, CX3CL1, IFN-α2, IL-12p70, IL-17A, TNF-α, IL-1ß, and IFN-γ, which is evidence of their shared inflammatory signature. IL-2 levels were elevated exclusively in RA patients, while MCP-1 and IL-10 were uniquely increased in SLE patients. Notably, TNF-α showed the most significant increase in SLE patients. IL-4 was elevated in SLE patients with nephritis, correlating with IL-6, IL-10, sCD40L, and IL-8, suggesting B cell involvement in lupus nephritis. The negative correlation between CX3CL1 and TNF-α with HDL in RA and SLE respectively, highlights the potential association of these inflammatory markers with cardiovascular risk. These findings underscore the complex cytokine interplay in RA and SLE. CX3CL1 emerges as a potential therapeutic target for RA, while TNF-α and IL-4 show promise as therapeutic targets for SLE.

Methyl-donor supplementation in women with systemic lupus erythematosus with different nutritional status: the protocol for a randomised, double-blind, placebo-controlled trial.

INTRODUCTION: DNA hypomethylation in patients with systemic lupus erythematosus (SLE) has been recently documented in the literature. Low levels of DNA methylation have been observed globally and in genes associated with immune and inflammatory pathways in SLE's CD4+T lymphocytes. Given that certain micronutrients can either donate methyl groups within one-carbon metabolism pathways or serve as cofactors for enzymes involved in the DNA methylation process, this randomised, double-blind, placebo-controlled trial aims to investigate whether a 3-month supplementation of folic acid and vitamin B12 will modulate the DNA methylation profile in subcutaneous adipose tissue (primary outcome) of women with SLE and normal weight or excess body weight. As secondary objectives, we will assess gene expression, telomere length and phenotypic characteristics (ie, clinical parameters, body weight and composition, abdominal circumference, food intake and disordered eating attitude, physical activity, lipid profile, serum concentrations of leptin, adiponectin, and cytokines). METHODS AND ANALYSIS: Patients will be classified according to their nutritional status by body mass index in normal weight or excess body weight. Subsequently, patients in each group will be randomly assigned to either a placebo or an intervention group (folic acid (400 mcg) and vitamin B12 (2000 mcg) supplementation). Endpoint evaluations will be conducted using both intention-to-treat and per-protocol analyses. This study has the potential to design new personalised nutritional approaches as adjunctive therapy for patients with SLE. ETHICS AND DISSEMINATION: This study has been reviewed and approved by the Ethical Committee from Clinical Hospital of the School of Medicine of the University of Sao Paulo, Brazil (CAAE.: 47317521.8.0000.0068). TRIAL REGISTRATION NUMBER: NCT05097365 (first version).

Ruptured aortic aneurysm in an adolescent with systemic lupus erythematosus. / Ruptura de aneurisma de aorta en una adolescente con lupus eritematoso sistémico.

Systemic lupus erythematosus (SLE) is a chronic, multisystem, autoimmune disease. Cardiovascular involvement is frequent; however, aneurysm and/or aortic dissection are rare entities with fatal evolution. The objective is to describe a rare and fatal complication of SLE in pediatrics and review the literature. We present the case of a 16-year-old girl with SLE with multisystem involvement without cardiovascular disease at diagnosis. She consulted for severe chest pain. Chest X-ray showed a dilated aortic arch with no cardiomegaly. The presence of a dissection was suspected, and an angiotomography was performed. A descending aortic aneurysm without a dissection flap was confirmed. Antihypertensive treatment was started. After a Valsalva maneuver, she presented an aneurysmal rupture. She died 12 hours after admission. Aneurysm and dissection are infrequent complications in pediatric SLE. As they have high mortality, it is essential to consider them in a patient with SLE and chest pain.

El lupus eritematoso sistémico (LES) es una enfermedad autoinmune, multisistémica y crónica. La afectación cardiovascular es frecuente, sin embargo, el aneurisma y/o la disección de aorta son entidades raras de evolución fatal. El objetivo es describir una complicación poco frecuente y fatal del LES en pediatría, y realizar una revisión de la literatura. Se presenta el caso de una mujer de 16 años con LES con afectación multisistémica, sin compromiso cardiovascular al diagnóstico. Consultó por dolor torácico grave. Radiografía de tórax sin cardiomegalia, con arco aórtico dilatado. Ante la sospecha de disección, se efectuó angiotomografía. Se confirmó aneurisma de aorta descendente sin flap de disección. Inició tratamiento antihipertensivo. Ante una maniobra de Valsalva, presentó ruptura aneurismática. Falleció a las 12 horas de su ingreso. El aneurisma y/o disección son complicaciones muy poco frecuentes en LES pediátrico. Al tener elevada mortalidad, es importante considerarlos ante un paciente con LES y dolor torácico.

Cognitive impairment in a Colombian cohort of patients with systemic lupus erythematosus: A cross-sectional study.

CONTEXT: Cognitive deficits are neuropsychiatric syndromes associated with systemic lupus erythematosus. In our context, there are no data on the frequency of cognitive deficit as a manifestation of neuropsychiatric SLE or the associated conditions. OBJECTIVE: To define determinants of cognitive deficit in a cohort of Colombian patients with SLE attending a third-level hospital. METHODS AND PATIENTS: This descriptive cross-sectional study included patients with SLE, explored the presence of cognitive impairment through screening testing using the Montreal Cognitive Assessment (MoCA test), and diagnostic confirmation with a specific neuropsychological test battery recommended by the American College of Rheumatology. Quality of life was assessed using the LupusCol questionnaire and depression using the Beck Depression Inventory. RESULTS: Most patients were women, with a median age of 37 years (IQR, 28.0 - 46.7). Most patients had a level of higher education or technical education. Fifty-nine (62.9%) patients presented with a normal MoCA test result ≥26 points, and 35 (37.1%) patients with a score <26 points that were considered abnormal. The comprehensive neuropsychological test battery was applied to 31 patients (33.0%) with an abnormal MoCA test. Forty-one patients (48.8%) had some degree of depression. The median loss of quality of life was 21.03% (IQR 10.2 - 40.3). 19 patients (20%) presented some degree of cognitive deficit, 15 (15.95% of the total sample) had cognitive impairment, and 4 (4.25%) had cognitive decline. In a logistic regression analysis using data from patients undergoing specific tests, variables related to cognitive deterioration were found to be associated with a lower quality of life, showing an adjusted odds ratio of 1.05 (CI 1.01-0.09). No association was demonstrated with SLEDAI, prednisolone use, cyclophosphamide use, and the presence of depression. CONCLUSION: In this study, it was found in 16% of patients evaluated with the complete neuropsychological test battery and in 37% with the MoCA screening test. Our results suggest that it is crucial to implement strategies to assess cognitive deficit, depression, and quality of life in the consultation of patients with SLE and to raise awareness among health providers who care for patients with lupus about their presence and impact.

Obesity as an aggravating factor of systemic lupus erythematosus disease: What we already know and what we must explore? - A rapid scoping review.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can affect various organs and systems. Symptoms of SLE can vary widely from person to person and over time, including fatigue, joint pain, skin rashes, fever, and inflammation of multiple organs. The association between SLE and excess body weight has been the subject of study, with evidence suggesting that overweight and obesity can worsen the disease´s clinical presentation. Obesity is linked to a state of low-grade chronic inflammation, which can exacerbate the inflammation present in SLE. Additionally, obesity may negatively impact treatment response, disease progression, and patient prognosis. Patients with SLE and obesity may face additional challenges in managing the disease, such as increased symptom severity, higher risk of cardiovascular and renal complications, and a reduced response to conventional treatments. Obesity can also influence the quality of life of patients with SLE, making a holistic approach that considers the individual's nutritional status essential. Therefore, understanding the relationship between obesity and SLE is crucial for optimizing treatment, improving clinical outcomes, and enhancing patients' quality of life. Further research is needed to elucidate the underlying pathophysiological mechanisms, develop more precise and personalized management strategies, and identify biomarkers that can predict disease prognosis and treatment response.

Predicting autoimmune diseases: A comprehensive review of classic biomarkers and advances in artificial intelligence.

Autoimmune diseases comprise a spectrum of disorders characterized by the dysregulation of immune tolerance, resulting in tissue or organ damage and inflammation. Their prevalence has been on the rise, significantly impacting patients' quality of life and escalating healthcare costs. Consequently, the prediction of autoimmune diseases has recently garnered substantial interest among researchers. Despite their wide heterogeneity, many autoimmune diseases exhibit a consistent pattern of paraclinical findings that hold predictive value. From serum biomarkers to various machine learning approaches, the array of available methods has been continuously expanding. The emergence of artificial intelligence (AI) presents an exciting new range of possibilities, with notable advancements already underway. The ultimate objective should revolve around disease prevention across all levels. This review provides a comprehensive summary of the most recent data pertaining to the prediction of diverse autoimmune diseases and encompasses both traditional biomarkers and the latest innovations in AI.

High Interleukin 21 Levels in Patients with Systemic Lupus Erythematosus: Association with Clinical Variables and rs2221903 Polymorphism.

Background: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoantibody production and diverse tissue and organ inflammatory affections. Interleukin 21 (IL-21) is implicated in B cell survival, proliferation, differentiation, class switching, and immunoglobulin production; therefore, it is considered a key cytokine in the pathogenesis of SLE. However, its association with disease activity and clinical phenotypes remains unclear. We aimed to evaluate the association of IL-21 levels with the disease activity and clinical phenotypes in patients with SLE. Also, we analyzed the IL21 polymorphisms associated with increased IL-21 levels. Methods: The IL-21 serum levels were determined using the enzyme-linked immunosorbent assay (ELISA) method. The rs2221903 and rs2055979 polymorphisms were assessed in 300 healthy controls (HCs) and 300 patients with SLE by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The levels of IL-21 were monitored during follow-up visits in 59 patients with SLE. Results: The patients with SLE showed higher IL-21 levels compared to the HCs. The IL-21 levels did not correlate with Mex-SLEDAI and were not different in patients with inactive, mild-moderate, and severe disease. The IL-21 levels were increased in patients with hematological affection. The ROC curve analysis revealed that the IL-21 levels had good predictive power in discriminating among patients with SLE and HCs. In a follow-up analysis, the levels of IL-21 remained higher in the patients with SLE even when the patients were in remission. Also, the rs2221903 polymorphism was associated with increased IL-21 levels. Conclusions: This study highlights the importance of IL-21 as a key cytokine in SLE. IL-21 levels are higher in patients with SLE and remain increased regardless of disease activity. According to the ROC analysis, IL-21 is a potential biomarker of SLE. Further longitudinal studies are needed to explore the relationship between IL-21 and the clinical phenotypes of SLE.

[Shrinking lung syndrome associated with systemic lupus erythematosus]. / Síndrome del pulmón encogido asociado a lupus eritematoso sistémico.

INTRODUCTION: Shrinking lung syndrome (SLS) is a rare and less-known manifestation of systemic lupus erythematosus (SLE). The aim of this study is to describe the demographic, clinical, functional, imaging characteristics, and treatment received in a cohort of patients diagnosed with SLS. METHODS: Clinical records were reviewed retrospectively in a cohort of patient with SLE and SLS followedup prospectively between 2007 to 2023 in the Rheumatology and Neumonology Units. RESULTS: Eleven SLS patients (10.3%) of 107 SLE patients were diagnosed. They were 81.8% female and 18.2% male. Median age was 30 years old (RIQ = 25-75% [25.5-41.5]). Clinical symptoms were dyspnea (72%), pleuritic pain (36%), but 27.3% of patients were asymptomatic at diagnosis. Respiratory functional evaluation was, median FEV1 / FVC : 86% (RIQ = 82-90), median FVC: 61% (RIQ = 38.5-71), median DLCO: 65% (RIQ = 48-69) and median DLCO/VA: 95% (RIQ = 89-106). High-resolution computed tomography of thorax (HRCT) showed atelectasis (54.5%), diafragmatic elevation (27.3%), normal (27.3%) and pleural effusion (9%). Patients were treated with systemic corticosteroids (100%); in 72.7% of them, associated to other immunosupressives: methotrexate (36%), mycophenolate (27.3%), hydroxychloroquine (27.3%) and azatioprine (18.2%). CONCLUSION: SLS prevalence was 10.3%, higher than reported in other studies of SLE. Dyspnea was the most clinical symptom. Suspicion of moderate restriction were determined with mild deterioration of DLCO. Atelectasis was the most frequent HCRT sign. Immunosupressive treatment was prescribed in all patients with systemic corticosteroids associated to other drugs.

Introducción: El síndrome de pulmón encogido (SPE) es una manifestación rara y poco conocida del lupus eritematoso sistémico (LES). El objetivo es describir las características demográficas, manifestaciones clínicas, funcionales, imagenológicas y tratamiento recibido en una cohorte de pacientes diagnosticados con SPE. Métodos: Se examinaron las historias clínicas de una cohorte de pacientes con LES seguidos prospectivamente desde 2007 al 2023 por los Servicios de Reumatología y Neumotisiología. Resultados: De 107 pacientes diagnosticados con LES, se hallaron 11 pacientes con SPE (10.3%), 81.8% fueron mujeres y 18.2 % varones; edad (mediana): 30 años (RIQ 25-75% = 25.5-41.5). Presentaron disnea 72%, dolor pleurítico 36%, y asintomáticos 27.3% al momento del diagnóstico. Funcionalmente presentaron FEV1 / FVC = 86% mediana, (RIQ = 82-90), FVC mediana 61% (RIQ= 38.5-71), DLCO mediana: 65% (RIQ = 48­69) y DLCO/VA mediana: 95% (RIQ = 89-106). Se observó en la tomografía de tórax de alta resolución (TACAR) atelectasias (54.5%), elevación del diafragma (27.3%), normalidad (27.3%) y derrame pleural (9%). Recibieron tratamiento con corticoides sistémicos (100%), asociados a otros inmunosupresores en 72.7%: metotrexato (36%), micofenolato (27.3%), hidroxicloroquina (27.3%) y azatioprina (18.2%). Conclusión: La prevalencia de SPE fue 10.3%, más alta que lo reportado en otras series de casos de LES. La disnea fue el síntoma principal de consulta. Los pacientes presentaron funcionalmente sospecha de restricción moderada y leve caída de la DLCO. La atelectasia fue el signo más frecuente en la TACAR. El tratamiento inmunosupresor fue indicado en todos los pacientes con corticoides sistémicos asociados usualmente a otros inmunosupresores.

Childhood-onset systemic lupus erythematosus associated with inborn errors of immunity: One or several conditions? / Lupus eritematoso sistémico pediátrico asociado a un error de la inmunidad innata: ¿una enfermedad o varias?

Childhood-onset systemic lupus erythematosus (cSLE) is a multisystem disease; its severity depends on the organs involved. Monogenic diseases have been described as predisposing to the onset of cSLE. Analytical and immunological tests are used for diagnostic confirmation. The main goal of treatment is remission and flare prevention. Here we describe the clinical case of a patient with prolonged febrile syndrome, arthralgias, and anemia, positive analytical tests for antinuclear antibodies and anti-DNA antibodies and low values of complement C3, C4, and C1q; so the patient was diagnosed with cSLE associated with C1q deficiency. Patients with C1q deficiency present with early onset of disease and significant target organ damage with nephritis. An early diagnosis of cSLE is important to ensure an early and appropriate treatment. Treatment may be personalized depending on the underlying defect that generates the subtype of lupus.

El lupus eritematoso sistémico pediátrico (LESp) es una enfermedad multisistémica, cuya gravedad depende de los órganos afectados. Se han descrito enfermedades monogénicas que predisponen a la aparición de LESp. Para la confirmación diagnóstica, se realizan pruebas analíticas e inmunológicas. El objetivo principal del tratamiento es la remisión de la enfermedad y la prevención de brotes. Se presenta un caso clínico de una paciente con síndrome febril prolongado, artralgias y anemia, con pruebas analíticas positivas para ANA, anti-ADN y valores bajos de complemento C3, C4 y C1q, por lo que se realizó diagnóstico de LESp asociado a deficiencia de C1q. Los pacientes con deficiencia de C1q presentan inicio temprano y daño importante a órganos blanco con nefritis. Realizar un diagnóstico oportuno de LESp es importante para garantizar un tratamiento temprano y adecuado. El tratamiento se podría individualizar dependiendo del defecto subyacente que genere el subtipo de lupus.

Colestasis, delirium y nocardiosis pulmonar en un varón con lupus eritematoso sistémico de inicio tardío / Cholestasis, delirium and pulmonary nocardiosis in a man with systemic lupus erythematosus of late onset

Resumen Se presenta el caso de un varón de 64 años que fue internado por delirium asociado a ictericia con patrón de colestasis en el hepatograma, y una masa en el pulmón derecho en el contexto de pérdida de peso y síndro me constitucional de 8 meses de evolución. Se realizó punción de la masa pulmonar cuyo cultivo desarrolló colonias blanquecinas identificadas como Nocardia cyria cigeorgica por espectrometría de masas (MALDI-TOF MS). Se llegó al diagnóstico de lupus eritematosos sistémico (LES) por presentar 8 de los criterios de acuerdo con el grupo SLICC 2012 y 24 puntos de acuerdo a los criterios EULAR/ACR 2019. La biopsia hepática mostró leve y variable infiltrado inflamatorio mixto en espacios porta, con ausencia de hepatitis de interfase y presencia de reacción ductular periférica. Se interpretaron estos hallazgos como vincu lados a hepatopatía por LES. El delirium fue interpretado como afectación neuroló gica por LES en base al descarte de otras enfermedades. Recibió tratamiento antibiótico y tras constatarse reducción del tamaño de la masa pulmonar se adminis traron pulsos de ciclofosfamida intravenosa. Evolucionó favorablemente, con normalización del hepatograma y el estado de conciencia, y recuperación del peso en forma progresiva. Al año se lo encontró en buen estado de salud. Justifica el reporte del caso la rara forma de presenta ción del LES de comienzo tardío, así como la nocardiosis pulmonar concomitante sin tratamiento inmunosupre sor previo.

Abstract A case is presented of a 64-year-old male patient who was admitted because of delirium, jaundice, a pattern of cholestasis in the liver profile and a right lung mass in the context of a constitutional syndrome and weight loss in the last eight months. The lung mass was punctured and the culture of the obtained material developed white colonies, identified by mass spectrometry (MALDI-TOF) as Nocardia cyriacigeorgica. Regarding the clinical diagnosis, it was considered as systemic lupus erythematosus (SLE), on the basis of fulfilling 8 criteria according to SLICC 2012 group, and 24 points according to EULAR/ACR 2019. The liver biopsy showed a mixt cellular infiltrate in portal spaces, with absence of interphase hepatitis and presence of peripheral ductular reaction. These findings were interpreted as liver compromise relate to SLE. Delirium was also considered as a neurological mani festation related to SLE on the basis of ruling out other causes. After being treated with antibiotics and documenting a reduction in the size of the lung mass he received cy clophosphamide in intravenous pulses, achieving normal ization of his liver profile and his state of consciousness, and a progressively weight recovering. A year after he was in good health. The report of this case is justified because of the rare presenting form of late onset SLE, as well as the concomi tant pulmonary nocardiosis in the absence of previous immunosuppressant treatment.

Complicaciones maternas y perinatales en gestantes con lupus: Estudio de casos y controles / Maternal and Perinatal Complications in Pregnant Women with Lupus: Case control Study

Objetivo: Determinar la frecuencia de complicaciones materno-perinatales y factores clínicos asociados a estos resultados en estantes con lupus. Métodos: Se realizó un estudio de casos y controles a partir de historias clínicas de pacientes con diagnóstico Lupus Eritematoso Sistémico en embarazo, entre 2010-2022 en una institución de salud en Medellín-Colombia. Éstas se clasificaron como casos (pacientes con resultados adversos materno-perinatales) y controles (pacientes sin resultados adversos). Resultados: Se incluyó un total de 67 pacientes (35 casos y 32 controles). Las complicaciones maternas más frecuentes fueron los trastornos hipertensivos asociados al embarazo (71,4 %), incluyendo preeclampsia y una presentación importante de partos pretérmino (68,6 %). La nefritis lúpica previa y durante el embarazo, fue más frecuente en los casos que en los controles (31,4 % versus 9,4 %). Los compromisos cardiovasculares, de mucosas y musculo-esquelético, fueron más frecuentes durante el embarazo (31,4 %, 40 % y 34,3 %, respectivamente), coincidiendo con mayor actividad del lupus, principalmente durante el embarazo. El compromiso cardiovascular y de mucosas durante el embarazo, así como tener síndrome antifosfolípido se relacionaron con desenlace materno-perinatal adverso. Conclusión: Componentes clínicos propios de la enfermedad como la nefritis lúpica, el síndrome antifosfolípido, el compromiso cardiovascular, y de mucosas podrían predisponer a desenlaces maternos y/o perinatales adversos como trastornos hipertensivos asociados al embarazo, pretérmino, restricción de crecimiento fetal, entre otros(AU)

Objective: To determine the frequency of maternal-perinatal complications and the clinical factors associated with these outcomes in pregnant women with lupus. Methods: A case-control study was conducted using the medical records of patients diagnosed with pregnancy and lupus in a healthcare institution in Medellin, Colombia, between 2010 and 2022. The patients were classified as cases (patients with adverse maternal-perinatal outcomes) and controls (patients without adverse outcomes). Results: A total of 67 patients (35 cases and 32 controls) were included. The most frequent maternal complications were pregnancyassociated hypertensive disorders (71.4%), including preeclampsia and a significant presentation of preterm deliveries (68.6%). Lupus nephritis prior to and during pregnancy was more frequent in cases than in controls (31.4% versus 9.4%). Cardiovascular, mucosal and musculoskeletal compromises were more frequent during pregnancy (31.4%, 40% and 34.3%, respectively), coinciding with greater lupus activity, mainly during pregnancy. Cardiovascular and mucosal involvement during pregnancy, as well as having antiphospholipid syndrome, were related to adverse maternal-perinatal outcome. Conclusion: Clinical components of the disease such as lupus nephritis, antiphospholipid syndrome, cardiovascular and mucosal involvement, are factors that may predispose these patients to adverse maternal and/or perinatal outcomes, such as hypertensive disorders associated with pregnancy, low birth weight, preterm, fetal growth restriction, among others(AU)

Updates in diagnosis and treatment of pediatric antiphospholipid syndrome.

PURPOSE OF REVIEW: This review offers an overview of the most important recent articles on pediatric APS. RECENT FINDINGS: Non-thrombotic extra criteria manifestations were prevalent in pediatric APS. Pregnancy morbidity has been described as the first manifestation of APS at youth age, impairing gestational outcomes. The 2023 APS criteria were developed for adult APS patients, and there is still a lack of pediatric-specific APS criteria. Catastrophic APS was more commonly reported as the initial manifestation of pediatric APS than in adults. Regarding treatment, direct oral anticoagulants have been recently approval for pediatric patients with venous thrombosis. New approaches have been proposed for severe cases, for arterial thrombosis, and rituximab for refractory cases. Recurrences typically occurred early and were associated with older age at diagnosis. Current studies highlighted the multifaceted nature of pediatric APS. Further large prospective multicenter studies evaluating new medications capable of reducing recurrence risk and improving prognosis in this population will be required.

Bilateral outer foveal microdefect in a patient with systemic lupus erythematosus using hydroxychloroquine - A case report.

INTRODUCTION: The association of outer foveal microdefect and LES or hydroxychloroquine use has not been established in current literature. CASE REPORT: We present the first reported case of bilateral outer foveal microdefect ina a patient with systemic lúpus erythematosus using hydroxycloroquine. DISCUSSION/CONCLUSION: While it is not possible to definitively attribute the described findings in our patient to HCQ use, it is important to be aware of the possibility that the outer foveal microdefect may be caused by this medication. Therefore, patients on chronic HCQ therapy should be informed about the risk of potential visual adverse effects, so that appropriate interventions can be implemented if necessary.

The Expression of Toll-like Receptors (TLR7 and TLR9) in Class III and Class IV of Recently Diagnosed Lupus Nephritis with 12-Month Follow-Up.

Renal involvement is an important cause of morbidity and mortality in systemic lupus erythematosus (SLE). The present study included patients with recently diagnosed Class III and Class IV lupus nephritis (LN) treated by Rheumatology who, upon the detection of alterations in their kidney function, were referred to Nephrology for the joint management of both medical specialties. The purpose of this study was to compare the plasma expression of Toll-Like Receptor 7 (TLR7) and TLR9 in healthy control (HC) subjects and newly diagnosed Class III and Class IV LN patients with 12-month follow-ups. The plasma expression of TLR7 and TLR9 proteins was determined by the ELISA method. A significant increase in the expression of TLR7 protein was found in Class III LN in the basal determination compared to the expression in the HC (p = 0.002) and at 12 months of follow-up (p = 0.03) vs. HC. The expression of TLR9 showed a behavior opposite to that of TLR7. TLR9 showed decreased protein expression in LN Class III patients' baseline and final measurements. The result was similar in the basal and final determinations of LN Class IV compared to the expression in HC. A significant decrease in SLEDAI -2K was observed at 12 months of follow-up in patients in Class III (p = 0.01) and Class IV (p = 0.0001) of LN. Complement C3 levels improved significantly at 12-month follow-up in Class IV patients (p = 0.0001). Complement C4 levels decreased significantly at 12-month follow-up in LN Class III compared to baseline (p = 0.01). Anti-DNA antibodies decreased significantly at 12 months of follow-up in Class IV LN (p = 0.01). A significant increase in proteinuria was found at 12 months of follow-up in Class III LN, compared to the baseline determination (p = 0.02). In LN Class IV, proteinuria decreased at 12 months of follow-up compared to baseline (p = 0.0001). Albuminuria decreased at 12 months of follow-up in LN Class IV (p = 0.006). Class IV LN, albuminuria also decreased at 12 months of follow-up (p = 0.009). Hematuria persisted in all patients and the glomerular filtration rate did not change. Three Class IV patients died before 12 months of follow-up from various causes. In conclusion, although the rheumatologic data appeared to improve, the renal function data remained inconsistent. Decreased expression of TLR9 and increased expression of TLR7 could be useful in the early diagnosis of Class III and Class IV LN is correct.

Partial long-term clinical improvement after a BCG challenge in systemic lupus erythematosus-prone mice.

Systemic Lupus Erythematosus (SLE) is an autoimmune disorder that causes a breakdown of immune tolerance. Current treatments mainly involve general immunosuppression, increasing the risk of infections. On the other hand, Bacillus Calmette-Guérin (BCG) has been investigated as a potential therapy for autoimmune diseases in recent years, prompting an ongoing investigation. This study aimed to evaluate the effect of BCG vaccination on early and late clinical presentation of SLE in a murine disease model. MRL/MPJ-Faslpr mice were immunized with BCG or treated with PBS as a control. The progress of the disease was evaluated at 27 days post-immunization (dpi) (early) and 56 dpi (late). Clinical parameters and proteinuria were monitored. Blood samples were collected for measurement of antinuclear antibodies (ANAs), anti-double-stranded DNA (anti-dsDNA), and cytokine determination was performed using ELISA. Samples collected from mice were analyzed by flow cytometry and histopathology. We observed a clinical improvement in BCG-treated mice, reduced proteinuria in the latter stages of the disease, and decreased TNF-α. However, BCG did not elicit significant changes in ANAs, anti-dsDNA, histopathological scores, or immune cell infiltration. BCG was only partially beneficial in an SLE mouse model, and further research is needed to determine whether the immunity induced by this vaccine can counteract lupus's autoimmune response.

Discordant Perception of Disease Activity Between Providers and Adolescents with Systemic Lupus Erythematosus: A Cohort Study.

Discordance in perception of disease activity between adolescent patients with lupus and their providers may influence disease outcomes. We found that patients endorsed higher perceptions of disease activity than providers. Discordance was present at all levels of disease activity, particularly in patients with high activity, nephritis, and/or taking corticosteroids or mycophenolate mofetil.

Exploring the Role of PD-1 in the Autoimmune Response: Insights into Its Implication in Systemic Lupus Erythematosus.

Despite advances in understanding systemic lupus erythematosus (SLE), many challenges remain in unraveling the precise mechanisms behind the disease's development and progression. Recent evidence has questioned the role of programmed cell death protein 1 (PD-1) in suppressing autoreactive CD4+ T cells during autoimmune responses. Research has investigated the potential impacts of PD-1 on various CD4+ T-cell subpopulations, including T follicular helper (Tfh) cells, circulating Tfh (cTfh) cells, and T peripheral helper (Tph) cells, all of which exhibit substantial PD-1 expression and are closely related to several autoimmune disorders, including SLE. This review highlights the complex role of PD-1 in autoimmunity and emphasizes the imperative for further research to elucidate its functions during autoreactive T-cell responses. Additionally, we address the potential of PD-1 and its ligands as possible therapeutic targets in SLE.

Assessment of the role of high-density lipoproteins and their immunomodulatory activity in systemic lupus erythematosus immunopathology.

OBJECTIVE: To explore the potential associations between high-density lipoprotein (HDL) levels and inflammasome components in the context of systemic lupus erythematosus (SLE). METHODS: A cross-sectional study was conducted. A group of 50 patients with SLE and 50 healthy controls matched by sex and similar age ranges were enrolled. Serum HDL cholesterol (HDL-C) and C reactive protein (CRP) levels were quantified. Serum cytokine levels, including IL-1ß and IL-6, were determined by ELISA. The gene expression of inflammasome-related genes in peripheral blood mononuclear cells was measured by quantitative real-time PCR. RESULTS: HDL-C levels were lower in the patients with SLE (p<0.05), and on segregation according to disease activity, those with active SLE had the lowest HDL-C levels. Patients with SLE presented higher concentrations of the serum inflammatory cytokines IL-1ß and IL-6 (p<0.0001) but similar levels of CRP to those in controls. A similar scenario was observed for the gene expression of inflammasome components, where all the evaluated markers were significantly upregulated in the SLE population. These results revealed significant negative correlations between HDL levels and disease activity, serum IL-6 and IL-1ß levels and the mRNA expression of NLRP3, IL-1ß and IL-18. In addition, significant positive correlations were found between disease activity and serum IL-1ß and between disease activity and the mRNA expression of IL-18, and interestingly, significant positive correlations were also observed between active SLE and serum IL-1ß and the mRNA expression of NLRP3. CONCLUSION: Our results suggest that HDL is essential for SLE beyond atherosclerosis and is related to inflammation regulation, possibly mediated by inflammasome immunomodulation.

Food consumption, physical activity and aerobic capacity in systemic lupus erythematosus patients with high cardiovascular risk.

Systemic Lupus Erythematosus (SLE) is a chronic, autoimmune and multisystemic rheumatic disease. Patients with SLE have decreased functional and aerobic capacity, as well as increased prevalence of Cardiovascular Diseases (CVD), which are the primary causes of morbimortality in this condition. Dietary intake and physical activity are well-known modifiable cardiovascular risk factors. The aim of this study is to describe food consumption, sedentary behavior, physical activity level, and functional and aerobic capacity in a sample of SLE patients with high cardiovascular risk. This was a cross-sectional study in which patients were assessed for (i) Demographic, anthropometric, and disease-related parameters; (ii) Food consumption; (iii) Physical activity level and sedentary behavior; (iv) Functional and aerobic capacity. Patients averaged 41.7 ± 9 years, and most were classified as overweight/obese (87%). Average macronutrient intake was within recommendations; however, fiber (16 ± 9g) and calcium (391 ± 217 mg) intakes were below, and sodium intake (2.9 ± 1.3 mg) was above recommendations. Besides, food consumption assessed by the Nova system showed a predominance of unprocessed foods (43.8 ± 14.0%TEI), although ultraprocessed food intake (20.0 ± 13.9%TEI) was slightly higher than that seen in the Brazilian population. Patients also exhibited high sedentary behavior (8.2 ± 2.2h) and only eighteen participants reached the minimum recommended amount of moderate-to-vigorous physical activity. Overall, patients had a low functional and aerobic capacity compared to the general population. Data from this study may help design dedicated clinical trials aiming to investigate the effects of lifestyle intervention to mitigate CVD in SLE.

Referrals for rheumatologic evaluation following a positive antinuclear antibody test result. A cross-sectional single center Brazilian study.

BACKGROUND: In general, patients are referred for rheumatological evaluation due to isolated laboratory abnormalities, especially antinuclear antibody (ANA) positivity, with the risk of more severe patients remaining on the waiting list for longer than desired. The aim of this study was to analyze the demographic, clinical, and laboratory information of patients referred to a specialized rheumatological care unit because of positive antinuclear antibody. METHODS: This is a retrospective study of 99 out of 1670 patients seen by the same rheumatologist between 01/01/2011 and 01/01/2019. Patients whose referrals were exclusively due to the ANA test result and the specialist's final diagnosis being "abnormal finding of serum immunological test" (ICD-10 R769) were included. Sociodemographic, clinical, and laboratory information were extracted from the consulting rheumatologist's chart. Descriptive statistics were used for data analysis. RESULTS: A total of 99 patients were included, most of whom were female (84.8%) with a median age of 49 years. At the moment of specialist's appointment, 97 patients (97.9%) repeated the ANA test, and 77 patients remained positive. Of these, only 35 (35.35%) were in a high titer range (greater than or equal to 1:320). Complete blood count for cytopenia's investigation was not performed in a high percentage of patients (22.2%), as well as urinalysis (31.3%). In addition, more than 70% of patients score 0 to 1 classification criteria for Systemic Lupus Erythematosus, according to SLE - ACR 1987 (American College of Rheumatology) and SLICC 2012 (Systemic Lupus International Collaborating Clinics). CONCLUSIONS: Most patients are still referred for specialized evaluation due to the misinterpretation of laboratory tests that were inappropriately requested in patients without clinical evidence of autoimmune rheumatic disease.