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).

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.

IRF5 Variants Are Risk Factors for Systemic Lupus Erythematosus in Two Mexican Populations.

INTRODUCTION: Interferon regulatory factor 5 ( IRF5 ) is one of the pivotal genes implicated in systemic lupus erythematosus (SLE) among diverse ethnic groups, including Europeans, Asians, Hispanics, and Africans. Notably, its significance appears particularly pronounced among Hispanic populations. Previous studies have identified several single-nucleotide variants within IRF5 , such as rs2004640G/T, rs2070197T/C, and rs10954213G/A, as associated with susceptibility to SLE among patients from Mexico City. However, the population of Yucatan, located in the Southeast of Mexico and characterized by a greater Amerindian genetic component, remains largely unexplored in this regard. OBJECTIVES: Our study aimed to replicate the observed association between IRF5 variants and susceptibility to SLE among patients from Central Mexico and Yucatan. Furthermore, we investigated the impact of IRF5 rs59110799G/T, a variant that has not been previously studied in SLE individuals. METHOD: Our study included 204 SLE patients and 160 controls from Central Mexico, as well as 184 SLE patients and 184 controls from Yucatan. All participants were females 18 years and older. We employed a TaqMan assay to detect the presence of the following single-nucleotide variants: rs2004640G/T, rs2070197T/C, rs10954213G/A, and rs59110799G/T. Furthermore, we utilized 2 distinct web tools and databases to predict the potential functional implications of IRF5 variants. RESULTS: In SLE patients from Central Mexico, several IRF5 alleles showed significant associations with the disease following adjustment by the Bonferroni test: the rs2070197C allele (odds ratio [OR], 2.08), the rs10954213A allele (OR, 1.59), and the rs59110799G allele (OR, 1.71). Conversely, among patients from Yucatan, the following alleles showed associations: rs2004640T (OR, 1.51), rs2070197C (OR, 1.62), rs10954213A (OR, 1.67), and rs59110799G (OR, 1.44). CONCLUSION: Our findings highlight genetic variations between Mexican populations and emphasize the role of IRF5 as a risk factor in SLE patients from both Central Mexico and Yucatan.

Development and Validation of Nosocomial Bacterial Infection Prediction Models for Patients With Systemic Lupus Erythematosus.

BACKGROUND: Hospital-acquired bacterial infections are associated with high morbidity and mortality rates in patients with systemic lupus erythematosus (SLE). This study aimed to develop and validate predictive models for the risk of hospital-acquired bacterial infections in patients with SLE. METHODS: A historical cohort study was designed for development, and another bidirectional cohort study was used for external validation. The risk of bacterial infection was assessed upon admission and after 5 days of hospitalization. Predictor selection employed the least absolute shrinkage and selection operator (LASSO) techniques. Multiple imputations were used to handle missing data. Logistic regression models were applied, and the properties of discrimination, calibration, and decision curve analysis were evaluated. RESULTS: The development cohort comprised 1686 patients and 237 events (14.1%) from 3 tertiary hospitals. The external validation cohort included 531 patients and 84 infection outcomes (15.8%) from 10 hospital centers in Colombia (secondary and tertiary level). The models applied at admission and after 120 hours of stay exhibited good discrimination (AUC > 0.74). External validation demonstrated good performance among patients from the same tertiary institutions where the models were developed. However, geographic validation at other institutions has been suboptimal. CONCLUSIONS: Two predictive models for nosocomial bacterial infections in patients with SLE are presented. All infection prevention recommendations should be maximized in patients at moderate/high risk. Further validation studies in diverse contexts, as well as clinical impact trials, are necessary before potential applications in research and clinical care.

Performance of the Systemic Lupus Erythematosus Risk Probability Index (SLERPI) in a cohort of Colombian population.

OBJECTIVE: To evaluate the performance of the Systemic Lupus Erythematosus Risk Probability Index (SLERPI) in Colombian patients with systemic lupus erythematosus (SLE). METHODS: The Colombian cohort included 435 SLE patients and 430 controls with other autoimmune diseases (ADs). Clinical and serological data were collected, and SLE was indicated by SLERPI scores > 7. The American College of Rheumatology (ACR)-1997, Systemic Lupus International Collaborating Clinics (SLICC)-2012, and European League Against Rheumatism (EULAR)/ACR-2019 criteria were used as reference standards. The impact of overt polyautoimmunity (PolyA) on SLERPI performance was assessed. Additionally, multivariate lineal regression analysis was performed to evaluate the contribution of SLERPI features to the overall SLERPI score. RESULTS: SLE patients had higher SLERPI scores (P < 0.0001), with almost 90% meeting "definite" lupus criteria. Main factors influencing SLERPI included immunological disorder (ß:44.75, P < 0.0001), malar/maculopapular rash (ß:18.43, P < 0.0001), and anti-nuclear antibody positivity (ß:15.65, P < 0.0001). In contrast, subacute cutaneous lupus erythematosus/discoid lupus erythematosus (ß:2.40, P > 0.05) and interstitial lung disease (ß:-21.58, P > 0.05) were not significant factors to the overall SLERPI score. SLERPI demonstrated high sensitivity for SLE, both for the overall SLE group and for those without overt PolyA (95.4% and 94.6%, respectively), but had relatively low specificity (92.8% and 93.7%, respectively). The model showed high sensitivity for hematological lupus (98.8%) and lupus nephritis (96.0%), but low sensitivity for neuropsychiatric lupus (93.2%). Compared to the ACR-1997, SLICC-2012 and EULAR/ACR-2019 criteria, SLERPI yielded the highest sensitivity and lowest specificity. CONCLUSION: SLERPI efficiently identified SLE patients in a Colombian cohort, showing high sensitivity but low specificity. The model effectively distinguishes SLE patients, even in the presence of concurrent overt PolyA. Key Points •SLERPI has a high sensitivity, but low specificity compared to ACR-1997, SLICC-2012 and EULAR/ACR-2019 criteria in the Colombian population. •Within the SLERPI score, immunological disorder, malar/maculopapular rash, and anti-nuclear antibody positivity are the strongest predictors of SLE. •SLERPI model can efficiently distinguish patients with SLE, regardless of concomitant overt PolyA. •SLERPI demonstrates high sensitivity in identifying hematological and nephritic subphenotypes of SLE.

Gene profiling of Epstein-Barr Virus and human endogenous retrovirus in peripheral blood mononuclear cells of SLE patients: immune response implications.

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.

Circulating extracellular vesicles in Systemic Lupus Erythematosus: physicochemical properties and phenotype.

OBJECTIVE: This study aimed to identify the physicochemical and phenotypic characteristics of circulating Extracellular Vesicles (EVs) in the plasma of patients with SLE, with or without Lupus Nephritis (LN), and their potential utility as disease biomarkers. METHODS: Plasma-circulating EVs were concentrated using differential centrifugation from adult female patients (n=38) who met the 'American College of Rheumatology/European Alliance of Associations for Rheumatology 2019' criteria for SLE diagnosis with (LN) or without LN (nLN), confirmed by renal biopsy. Controls (n=18) were healthy volunteers matched by gender and similar age. The structure, size and Energy Dispersion Spectrum (EDS) of EVs were observed by electron microscopy. The surface charge and size distribution were evaluated using dynamic light scattering. The counts and phenotype of EVs from patients (SLE-EVs) and controls (Ctrl-EVs) were obtained using flow cytometry. Non-parametric statistical tests and exploratory analysis of multiple variables were performed. The discriminatory power of some variables as potential biomarkers of the disease was also evaluated. RESULTS: Circulating EVs were heterogeneous in morphology and size, but SLE-EVs reached larger diameters than Ctrl-EVs (p<0.0001). Small SLE-EVs and large SLE-EVs were increased compared with Ctrl-EV (p<0.0001 and p<0.05, respectively). Likewise, patients with SLE (LN or nLN) had higher concentrations of large EVs compared with controls (p<0.001 and p<0.0001, respectively). SLE-EVs showed a different EDS (p<0.001) and were less electronegative (p<0.0001) than Ctrl-EVs. EV-CD45+, EV-CD14+ and EV-IgM+ were more frequent in patients with SLE compared with controls (p<0.001, p<0.05 and p<0.001, respectively). The concentrations of large EVs and EV-IgM+ allowed better discrimination of patients from controls. CONCLUSIONS: Plasma-circulating EVs from patients with SLE with and without nephritis are increased in peripheral blood and have different physicochemical properties than controls. Characteristics of EVs such as larger size and the presence of IgM on the surface could help discriminate patients from controls.

[Epidemiological, clinical, and biochemical characteristics of patients in the LUPUS-IMMex cohort]. / Características epidemiológicas, clínicas y bioquímicas de los pacientes en la cohorte LUPUS-IMMex.

Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can affect multiple organs and body systems. Objective: To describe the sociodemographic, clinical, and biochemical characteristics of the Lupus-IMMS-Mexico (LUPUS-IMMex) patient cohort from a tertiary-level center. Material and methods: Observational descriptive study of 160 patients with diagnosis of SLE belonging to the aforementioned cohort. Various variables were analyzed at the time of diagnosis. For quantitative variables, normality tests were applied, followed by measures of central tendency and dispersion according to their distribution. For categorical variables, frequencies and percentages were calculated. Results: 81.87% of the patients were female, with a median age at diagnosis of 28 years. 18.12% had a family history of SLE, and concurrently with SLE, 32.50% had hypertension, and 11.25% had antiphospholipid syndrome. The most common clinical manifestation was joint involvement (68.12%), renal (49.37%) and hematological (43.75%) manifestations. Conclusions: SLE affects millions globally. Lack of awareness leads to delayed diagnoses, suboptimal management, and diminished quality of life. After analyzing 160 patients with SLE, their clinical, socioeconomic, and therapeutic characteristics are largely like other cohorts, with differences attributable to ethnic and geographical influences. Informing patients about SLE and providing reliable resources are essential for self-care. Awareness promotes research, therapies, and enhances medical care and the lives of patients globally.

Introducción: el lupus eritematoso sistémico (LES) es una enfermedad autoinmunitaria crónica que puede afectar a múltiples órganos y sistemas del cuerpo. Objetivo: describir las características sociodemográficas, clínicas y bioquímicas de la cohorte de pacientes Lupus-IMMS-México (LUPUS-IMMex) de un hospital de tercer nivel. Material y métodos: estudio descriptivo observacional de 160 pacientes con diagnóstico de LES de la cohorte mencionada. Se analizaron diversas variables al momento del diagnóstico. Para variables cuantitativas se aplicaron pruebas de normalidad y posteriormente medidas de tendencia central y dispersión de acuerdo con su distribución. Para variables categóricas se calcularon frecuencias y porcentajes. Resultados: 81.87% de los pacientes fueron del sexo femenino, con mediana de edad al diagnóstico de 28 años. El 18.12% tenían antecedentes familiares de LES y concomitante al LES, hipertensión (32.50%) y síndromes antifosfolípidos (11.25%). Las afecciones clínicas más frecuentes fueron la articular (68.12%), la renal (49.37%) y la hematológica (43.75%). Conclusiones: el LES afecta a millones de personas globalmente. La falta de conciencia lleva a diagnósticos tardíos, manejo deficiente y baja calidad de vida. Tras analizar 160 pacientes con LES, sus características clínicas, socioeconómicas y terapéuticas son mayormente similares a otras cohortes, con diferencias atribuibles a influencias étnicas y geográficas. Informar a los pacientes sobre el LES y brindar recursos confiables es esencial para el autocuidado. La sensibilización fomenta la investigación, las terapias y mejora la atención médica y la vida de pacientes a nivel global.

[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.

Experiencing pregnancy in the context of lupus and antiphospholipid syndrome: a grounded theory.

OBJECTIVE: To understand the meanings attributed to pregnancy in the context of Lupus and antiphospholipid syndrome by women and healthcare professionals. METHOD: Qualitative research, using Symbolic Interactionism as a theoretical framework and Grounded Theory, a constructivist perspective. Data were collected between January and August 2022, through online interviews with 27 women with Lupus located on the social network Facebook and in-person or remote interviews with 12 healthcare professionals. RESULTS: The theoretical model constructed has two categories: "Equal conditions, distinct experiences: experiencing the gestational process" shows that obstetric complications and lack of connection with healthcare professionals trigger negative meanings to the experience; and "Therapeutic management interfering in the attribution of meanings to the experience", demonstrates that the way women interact with healthcare professionals and how they manage treatment favors a positive reframing. FINAL CONSIDERATIONS: The meanings attributed to pregnancy are elaborated and modified according to the interpretation of previous and current experiences, healthcare trajectory and interactions with healthcare professionals. Previous guidance, planning, bonding and trust in healthcare professionals enable positive meanings, while obstetric complications, unqualified assistance and lack of bonding with professionals provide negative meanings.

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)

Coronary Artery Calcification Progression in Patients With Systemic Lupus Erythematosus.

OBJECTIVE: To evaluate the progression of coronary artery calcification (CAC) and associated risk factors in a systemic lupus erythematosus (SLE) cohort. METHODS: We reassessed the presence of CAC in patients with SLE who were screened 9 years before, using multidetector computed tomography. Clinical variables (cumulated disease activity and damage accrual), antiphospholipid syndrome and SLE serology, and cardiovascular (CV) risk factors (hypertension, BMI [kg/m2], modified Framingham risk score, lipid profile, menopausal status) were assessed longitudinally. RESULTS: We included 104 patients from the parent study. Most of them were women (94.2%), with a mean age of 41.0 (SD 8.3) years and mean disease duration of 14.8 (SD 2.9) years. We documented CAC in 17 patients (16.3%). Seven cases were from the parent study and 10 were incident cases. The cumulative incidence of CAC was 9% and the incidence density was 1 per 100 person-years. CAC occurred more frequently in the age groups 30-39 years and 40-44 years. All patients with previous CAC had worsening of their calcium indexes, and none developed clinical CV events. When comparing prevalent CAC cases (n = 17) vs patients without calcification (n = 87), both groups were similar in traditional CV risk factors, disease duration, Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) area under the curve (AUC), and Systemic Lupus International Collaborating Clinics (SLICC) score, but were more likely to be postmenopausal and have higher apolipoprotein B (apoB) levels. Patients with previous CAC had higher apoB levels, SLEDAI-2K AUC scores, and anticardiolipin IgG antibodies than incident cases. CONCLUSION: CAC in patients with SLE progressed over time but was not associated with adverse CV events during the first 9 years of follow-up. ApoB levels and postmenopausal status might be associated with this progression.

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.

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.