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OBJECTIVES: To identify the predictive factors of first hospitalization and associated variables to the main causes of hospitalizations in lupus patients from a Latin American cohort. METHODS: The first hospitalization after entry into the cohort during these patients' follow-up due to either lupus disease activity and/or infection was examined. Clinical and therapeutic variables were those occurring prior to the first hospitalization. Descriptive statistical tests, multivariable logistic, and Cox regression models were performed. RESULTS: 1341 individuals were included in this analysis; 1200 (89.5%) were women. Their median and interquartile range (IQR) age at diagnosis were 27 (20-37) years and their median and IQR follow up time were 27.5 (4.7-62.2) months. A total of 456 (34.0%) patients were hospitalized; 344 (75.4%), 85 (18.6%) and 27 (5.9%) for disease activity, infections, or both, respectively. The predictors of the first hospitalization regardless of its cause were: medium (HR 2.03(1.27-3.24); p = 0.0028) and low (HR 2.42(1.55-3.79); p < 0.0001) socioeconomic status, serosal (HR 1.32(1.07-1.62); p = 0.0074) and renal (HR 1.50(1.23-1.82); p < 0.0001) involvement. Antimalarial (AM) use (HR 0.61(0.50-0.74); p < 0.0001) and achieving remission (HR 0.80(0.65-0.97); p = 0.0300) were negative predictors. CONCLUSIONS: The first hospitalization was associated with worse socioeconomic status and serosal and renal involvement. Conversely, AM use and achieving remission were associated with a lower risk of hospitalizations.
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OBJECTIVES: To measure the expression level of the vacuolar protein sorting 13 (VPS13) gene and stimulator of interferon genes (STING) in patients with SLE with and without reported neuropsychiatric symptoms to establish their possible role in the pathogenesis of neuropsychiatric SLE (NPSLE). METHODS: This study included 100 subjects: 50 patients diagnosed with SLE and 50 age-matched and sex-matched healthy participants as the control group. The patients with SLE were further subdivided into NPSLE and non-NPSLE groups. All the subjects underwent rheumatological, neurological and psychological evaluation, MRI, VPS13C gene and STING expression assessment via quantitative real-time PCR. RESULTS: Seventy-eight per cent of the SLE group were classified as non-NPSLE, and 22% were classified as NPSLE. Positive MRI results were found in 55% of the patients with NPSLE and 7.7% of the patients without NPSLE.VPS13C expression levels were decreased in the patients with SLE compared with the control (p<0.001), while STING expression levels showed higher levels in the patients in comparison with the control (p<0.001). Both markers showed significant differences between the MRI-positive and MRI-negative groups.At a cut-off value of 0.225 for the VPS13C assessment and a cut-off value of 3.15 for STING expression, both markers were able to distinguish patients with NPSLE from those who were non-NPSLE; however, VPS13C performed better. CONCLUSION: The VPS13C expression levels were decreased in patients with NPSLE compared with patients without NPSLE, while STING expression levels showed higher levels in NPSLE. Both were associated with the MRI findings. To distinguish patients with NPSLE from those without it, the VPS13C assessment performed better.
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Vasculitis por Lupus del Sistema Nervioso Central , Imagen por Resonancia Magnética , Proteínas de la Membrana , Humanos , Femenino , Adulto , Masculino , Proteínas de la Membrana/genética , Vasculitis por Lupus del Sistema Nervioso Central/inmunología , Imagen por Resonancia Magnética/métodos , Estudios de Casos y Controles , Persona de Mediana Edad , Adulto Joven , Proteínas de Transporte Vesicular/genética , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/psicología , Lupus Eritematoso Sistémico/inmunología , ProteínasRESUMEN
OBJECTIVE: To evaluate both humoral and cellular immune responses to the COVID-19 messenger RNA (mRNA; BNT162b2) vaccine in patients with childhood-onset SLE (cSLE) compared with healthy controls and patient controls (kidney transplant (KTx) recipients). METHODS: This single-centre, cross-sectional and case-control study included 16 patients with cSLE, 19 healthy controls and 19 KTx recipients. We assessed SARS-CoV-2-specific humoral (anti-SARS-CoV-2 IgG, neutralising antibody (nAb)) and cellular (interferon gamma release assay (IGRA)) immune responses at least 1 month after administration of two doses of the mRNA vaccine. RESULTS: Humoral immune response rates (anti-SARS-CoV-2 IgG and nAb seropositivity) in patients with cSLE were comparable to healthy controls (100% vs 100% and 100% vs 95%, respectively) but significantly higher than in KTx recipients (74% and 42%, p<0.05 for both). Cellular immune response rate measured by IGRA was lower in patients with cSLE compared with healthy controls (56.3% vs 89.5%, p=0.050) and comparable to KTx recipients (63%). IGRA-negative patients with cSLE had significantly lower total leucocyte and lymphocyte counts at vaccination time as compared with their counterparts (p=0.008 and p=0.001, respectively). No differences were found in disease activity or immunosuppressive therapies between IGRA-negative and IGRA-positive patients with cSLE. CONCLUSION: Patients with cSLE showed robust humoral but compromised cellular immune responses to the COVID-19 mRNA vaccine, associated with lower lymphocyte counts. These findings highlight the need for further research to enhance vaccine efficacy in this vulnerable group.
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Anticuerpos Antivirales , Vacuna BNT162 , COVID-19 , Inmunidad Celular , Inmunidad Humoral , Lupus Eritematoso Sistémico , SARS-CoV-2 , Humanos , Femenino , Masculino , Estudios de Casos y Controles , COVID-19/prevención & control , COVID-19/inmunología , Lupus Eritematoso Sistémico/inmunología , Estudios Transversales , SARS-CoV-2/inmunología , Anticuerpos Antivirales/sangre , Adulto , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Trasplante de Riñón , Niño , Adolescente , Inmunoglobulina G/sangre , Adulto JovenRESUMEN
OBJECTIVES: This study aims to elucidate the microbial signatures associated with autoimmune diseases, particularly systemic lupus erythematosus (SLE) and inflammatory bowel disease (IBD), compared with colorectal cancer (CRC), to identify unique biomarkers and shared microbial mechanisms that could inform specific treatment protocols. METHODS: We analysed metagenomic datasets from patient cohorts with six autoimmune conditions-SLE, IBD, multiple sclerosis, myasthenia gravis, Graves' disease and ankylosing spondylitis-contrasting these with CRC metagenomes to delineate disease-specific microbial profiles. The study focused on identifying predictive biomarkers from species profiles and functional genes, integrating protein-protein interaction analyses to explore effector-like proteins and their targets in key signalling pathways. RESULTS: Distinct microbial signatures were identified across autoimmune disorders, with notable overlaps between SLE and IBD, suggesting shared microbial underpinnings. Significant predictive biomarkers highlighted the diverse microbial influences across these conditions. Protein-protein interaction analyses revealed interactions targeting glucocorticoid signalling, antigen presentation and interleukin-12 signalling pathways, offering insights into possible common disease mechanisms. Experimental validation confirmed interactions between the host protein glucocorticoid receptor (NR3C1) and specific gut bacteria-derived proteins, which may have therapeutic implications for inflammatory disorders like SLE and IBD. CONCLUSIONS: Our findings underscore the gut microbiome's critical role in autoimmune diseases, offering insights into shared and distinct microbial signatures. The study highlights the potential importance of microbial biomarkers in understanding disease mechanisms and guiding treatment strategies, paving the way for novel therapeutic approaches based on microbial profiles. TRIAL REGISTRATION NUMBER: NCT02394964.
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OBJECTIVE: To estimate real-life European Alliance of Associations for Rheumatology (EULAR)/European Renal Association (ERA)-European Dialysis and Transplantation Association (EDTA) response rates and predictors for no response in patients with lupus nephritis (LN) managed with conventional immunosuppressive therapies. METHODS: Ambidirectional cohort study of patients with new-onset LN (period 2014-to date). Response rates in the first year were calculated, and all treatment modifications were recorded. Univariate and multivariate regression analyses were performed to assess determinants of failure to respond at 12 months. RESULTS: 140 patients were included (81.4% women, median (IQR) age at LN diagnosis 38 (22) years). Among them, 32.1% presented with nephrotic range proteinuria, 28.6% with glomerular filtration rate <60 mL/min, 76.6% had proliferative and 19.7% class V LN. Initial treatment consisted of cyclophosphamide in 51.4% of patients (84.7% high-dose, 15.3% low-dose) and mycophenolate in 32.1%. 120 patients had available data at 12 months. EULAR/ERA-EDTA renal response rates at 3, 6 and 12 months were achieved by 72.6%, 78.5% % and 69.2% of patients, respectively. In multivariate analysis, increased Chronicity Index at baseline was associated with failure to achieve either complete or partial response at 12 months (OR 2.26, 95% CI 1.35 to 3.77). Notably, 20% of patients required treatment modifications due to suboptimal response during the first 12 months, with the addition of or switch to a different immunosuppressive drug in seven and nine patients, respectively. CONCLUSIONS: More than two-thirds of patients with LN attain EULAR/ERA-EDTA response rates by 12 months, but 20% require therapy modifications within this time period. Patients with increased chronicity in baseline biopsy, when combined with histological activity, are at higher risk for a lack of clinical response.
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Tasa de Filtración Glomerular , Inmunosupresores , Nefritis Lúpica , Humanos , Femenino , Masculino , Inmunosupresores/uso terapéutico , Adulto , Persona de Mediana Edad , Nefritis Lúpica/tratamiento farmacológico , Resultado del Tratamiento , Ciclofosfamida/uso terapéutico , Ácido Micofenólico/uso terapéutico , Adulto JovenAsunto(s)
Hidroxicloroquina , Lupus Eritematoso Sistémico , Inhibidores de Agregación Plaquetaria , Trombosis , Humanos , Hidroxicloroquina/uso terapéutico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/complicaciones , Inhibidores de Agregación Plaquetaria/uso terapéutico , Trombosis/tratamiento farmacológico , Trombosis/etiología , Femenino , Adulto , Masculino , Antirreumáticos/uso terapéutico , Persona de Mediana EdadRESUMEN
OBJECTIVES: In childhood-onset SLE (cSLE), patients have an increased risk of premature atherosclerosis. The pathophysiological mechanisms for this premature atherosclerosis are not yet completely understood, but besides traditional risk factors, the endothelium plays a major role. The first aim of this study was to measure levels of SLE-associated markers involved in endothelial cell (EC) function and lipids in a cSLE cohort longitudinally in comparison with healthy controls (HC). Next aim was to correlate these levels with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and nailfold capillaroscopic patterns. METHODS: Blood serum samples, videocapillaroscopy images and patient characteristics were collected in a multicentre longitudinal cSLE cohort and from age and sex comparable HC. Disease activity was evaluated by SLEDAI. A total of 15 EC markers and six lipids were measured in two longitudinal cSLE samples (minimum interval of 6 months) and in HC. Nailfold videocapillaroscopy images were scored according to the guidelines from the EULAR Study Group on Microcirculation in Rheumatic Diseases. RESULTS: In total, 47 patients with cSLE and 42 HCs were analysed. Median age at diagnosis was 15 years (IQR 12-16 years). Median time between t=1 and t=2 was 14.5 months (IQR 9-24 months). Median SLEDAI was 12 (IQR 6-18) at t=1 and 2 (IQR 1-4) at t=2. Serum levels of angiopoietin-2, CCL2, CXCL10, GAS6, pentraxin-3, thrombomodulin, VCAM-1 and vWF-A2 were elevated in cSLE compared with HC at t=1. While many elevated EC markers at t=1 normalised over time after treatment, several markers remained significantly increased compared with HC (angiopoietin-2, CCL2, CXCL10, GAS6, thrombomodulin and VCAM-1). CONCLUSION: In serum from patients with cSLE different markers of endothelial activation were dysregulated. While most markers normalised during treatment, others remained elevated in a subset of patients, even during low disease activity. These results suggest a role for the dysregulated endothelium in early and later phases of cSLE, possibly also during lower disease activity. TRIAL REGISTRATION NUMBER: NL60885.018.17.
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Biomarcadores , Lupus Eritematoso Sistémico , Angioscopía Microscópica , Humanos , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/fisiopatología , Femenino , Masculino , Niño , Adolescente , Biomarcadores/sangre , Estudios Longitudinales , Angioscopía Microscópica/métodos , Endotelio Vascular/fisiopatología , Edad de Inicio , Células Endoteliales , Índice de Severidad de la Enfermedad , Estudios de Casos y Controles , Trombomodulina/sangre , Lípidos/sangre , Aterosclerosis/sangre , Aterosclerosis/fisiopatologíaRESUMEN
BACKGROUND: Rituximab is associated with high infection rates, but studies of infections following rituximab in youth with childhood-onset SLE (cSLE) are limited. We conducted a retrospective longitudinal cohort study to assess the incidence of hospitalised infections following rituximab among children with cSLE and to assess changes in hospital-based rituximab administration over time. METHODS: Youth ages 2-21 years with an International Classification of Diseases (ICD) code for SLE who received rituximab during admission to a Pediatric Health Information System hospital from 2009 to 2021 were included. Incidence rates for infections requiring hospitalisation over the 12 months following first rituximab administration were calculated. Rituximab use by year of hospital discharge was tabulated. RESULTS: We identified 1567 children with cSLE who received rituximab. 219 children were admitted with an infection within 1 year after first rituximab administration, for an incidence rate of 140 cases per 1000 patient-years. Seven children (0.44%) died during a hospitalisation with an infection in the year following rituximab administration. The most common hospitalised infections were bacterial pneumonia, sepsis and cellulitis. 12 children were hospitalised with COVID-19, none of whom died. Hospitalisations with rituximab administered decreased from 2019 to 2021. CONCLUSIONS: In this cohort of patients with cSLE who received inpatient treatment with rituximab, we observed a 14% rate of hospitalisation with infection in the year following rituximab administration among youth with cSLE. Rituximab use declined during the COVID-19 pandemic. No fatalities with COVID-19 were observed. Given the lack of outpatient data, including doses of concomitant medications and disease activity measures, further research is needed to identify risk factors for infection following rituximab among children with cSLE.
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Hospitalización , Lupus Eritematoso Sistémico , Rituximab , Humanos , Rituximab/uso terapéutico , Rituximab/efectos adversos , Rituximab/administración & dosificación , Adolescente , Niño , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/complicaciones , Femenino , Estudios Retrospectivos , Masculino , Preescolar , Hospitalización/estadística & datos numéricos , Estudios Longitudinales , Incidencia , Adulto Joven , COVID-19/epidemiología , SARS-CoV-2RESUMEN
Myocarditis is a potentially life-threatening inflammatory disease of the myocardium, often resulting from infectious and immune-mediated responses. Clinical presentation in severe cases often results in a devastating illness requiring extracorporeal membrane oxygenation support as a result of cardiogenic shock. Although endomyocardial biopsy is still considered the gold standard for diagnosis, it often reveals nonspecific lymphocytic infiltration. Because the precise cause is usually unknown, the initial treatment typically involves immunosuppression and frequent assessment of myocardial contractility. This report presents 3 rare cases of autoimmune diseases (polymyositis, immunoglobulin G4-related disease, and systemic lupus erythematosus) that require extracorporeal membrane oxygenation support as a result of fulminant myocarditis, including their follow-up periods.
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Oxigenación por Membrana Extracorpórea , Miocarditis , Humanos , Miocarditis/terapia , Miocarditis/diagnóstico , Miocarditis/fisiopatología , Miocarditis/inmunología , Oxigenación por Membrana Extracorpórea/métodos , Masculino , Femenino , Adulto , Biopsia , Persona de Mediana Edad , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/terapia , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/complicaciones , Miocardio/patología , Miocardio/inmunología , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/terapia , Choque Cardiogénico/terapia , Choque Cardiogénico/etiología , Choque Cardiogénico/diagnóstico , Resultado del Tratamiento , Enfermedad Relacionada con Inmunoglobulina G4/diagnóstico , Enfermedad Relacionada con Inmunoglobulina G4/terapia , Enfermedad Relacionada con Inmunoglobulina G4/complicacionesRESUMEN
OBJECTIVES: To evaluate the safety, tolerability, pharmacokinetics (PK), biomarker response and efficacy of E6742 in a phase I/II study in patients with systemic lupus erythematosus (SLE). METHODS: Two sequential cohorts of patients with SLE were enrolled and randomised to 12 weeks of two times per day treatment with E6742 (100 or 200 mg; n=8 or 9) or placebo (n=9). The primary endpoint was safety, the secondary endpoints were PK and interferon gene signature (IGS), and the exploratory endpoints were efficacy and biomarker. RESULTS: The proportion of patients with any treatment-emergent adverse events (TEAEs) was 58.8% in the E6742 group (37.5% (3/8 patients) for 100 mg; 77.8% (7/9 patients) for 200 mg) and 66.7% (6/9 patients) in the placebo group. No Common Terminology Criteria for Adverse Events≥Grade 3 TEAEs occurred. PK parameters were similar to these in previous phase I studies in healthy adults. The IGS and levels of proinflammatory cytokines after ex-vivo challenge with a Toll-like receptor 7/8 agonist were immediately decreased by E6742 treatment. The response rate of the British Isles Lupus Assessment Group-based Composite Lupus Assessment at week 12 was 37.5% (3/8 patients) for E6742 100 mg, 57.1% (4/7 patients) for E6742 200 mg and 33.3% (3/9 patients) for placebo group. CONCLUSIONS: E6742 had a favourable safety profile and was well tolerated, with suppression of IGS responses and preliminary efficacy signals in patients with SLE. These results provide the first clinical evidence to support E6742 in the treatment of SLE, and support larger, longer-term clinical trials. TRIAL REGISTRATION NUMBER: NCT05278663.
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Biomarcadores , Lupus Eritematoso Sistémico , Receptor Toll-Like 7 , Receptor Toll-Like 8 , Humanos , Lupus Eritematoso Sistémico/tratamiento farmacológico , Femenino , Adulto , Masculino , Receptor Toll-Like 7/antagonistas & inhibidores , Persona de Mediana Edad , Método Doble Ciego , Resultado del Tratamiento , Receptor Toll-Like 8/antagonistas & inhibidoresRESUMEN
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by a significant health burden. There is an essential need for novel biomarkers and therapeutic targets to improve diagnosis and management. Mendelian randomization (MR) was applied to explore causal links between SLE and various biomarkers like immune cells, metabolites, and inflammatory cytokines using multiple databases. Initially, biomarkers significantly associated with SLE were identified. Bidirectional MR helped clarify these relationships, and a two-step mediation MR examined their effects on SLE risk. Intersection analysis was used to identify biomarkers with consistent effects across datasets. Four biomarkers were identified as having significant associations with SLE risk: 1-palmitoyl-2-arachidonoyl-GPI levels [odds ratio (OR), 1.379; 95% confidence interval (CI), 1.180 to 1.613; FDR, 0.046], IL-17A levels (OR, 2.197; 95% CI, 1.412 to 3.418; FDR, 0.044), N-acetyl-aspartyl-glutamate (NAAG) levels (OR, 0.882; 95% CI, 0.831 to 0.936; FDR, 0.030), and ribitol levels (OR, 0.743; 95% CI, 0.644 to 0.857; FDR, 0.012). Bidirectional MR showed an inverse effect of NAAG on IL-17A levels (OR, 0.978; 95% CI, 0.962 to 0.994; p = 0.006). Mediation analysis indicated that NAAG influenced SLE risk both directly (beta = - 0.108) and indirectly through IL-17A (beta = - 0.018), highlighting the potential mediating role of IL-17A. After expanding the significance criteria to p < 0.05, intersection analysis across multiple datasets revealed 29 biomarkers with consistent beta directions, including 19 potential risk factors (beta > 0) and 10 protective factors (beta < 0) for SLE. This research has revealed significant genetic associations with SLE and demonstrated that IL-17A mediates the relationship between NAAG levels and SLE risk, highlighting potential new targets for personalized therapeutic interventions. Key Points ⢠This study employs MR to identify significant genetic associations between various biomarkers and SLE, providing novel insights into potential biomarkers and therapeutic targets. ⢠Four key biomarkers were identified as significantly associated with SLE risk: 1-palmitoyl-2-arachidonoyl-GPI, IL-17A, N-acetyl-aspartyl-glutamate (NAAG), and ribitol. ⢠The findings suggest that NAAG levels have a protective effect against SLE, partly mediated through IL-17A, indicating a complex interplay between these biomarkers in the pathogenesis of SLE. ⢠Intersectional analysis across multiple datasets revealed 29 biomarkers with consistent effects on SLE risk, highlighting new directions for future research and potential personalized therapeutic strategies.
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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.
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Lupus Eritematoso Sistémico , Humanos , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/epidemiología , Lupus Eritematoso Sistémico/sangre , Femenino , Masculino , Adulto , México/epidemiología , Persona de Mediana Edad , Adulto Joven , Estudios de Cohortes , AdolescenteRESUMEN
Paediatric systemic lupus erythematosus (pSLE) management and research could be enhanced by a mobile health application (app); however, no app designed for pSLE is currently available. A development and design committee comprising of patients, parents/caregivers and other stakeholders met to inform development and design of an app specific for pSLE. This meeting report summarises the group's discussions and recommendations that could help create a useful and desirable app or mobile health tool for the pSLE community.
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Cuidadores , Lupus Eritematoso Sistémico , Aplicaciones Móviles , Telemedicina , Humanos , Lupus Eritematoso Sistémico/terapia , NiñoRESUMEN
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.
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Biomarcadores , Vesículas Extracelulares , Lupus Eritematoso Sistémico , Nefritis Lúpica , Fenotipo , Humanos , Femenino , Vesículas Extracelulares/metabolismo , Adulto , Lupus Eritematoso Sistémico/sangre , Biomarcadores/sangre , Nefritis Lúpica/sangre , Nefritis Lúpica/diagnóstico , Persona de Mediana Edad , Estudios de Casos y Controles , Citometría de Flujo/métodosRESUMEN
OBJECTIVES: To compare the sensitivity of 2019 European Alliance of Associations for Rheumatology/American College of Rheumatology (EULAR/ACR) classification criteria against 1997 ACR criteria for systemic lupus erythematosus (SLE), for incident SLE cases in the presumably complete population-based Nor-SLE cohort from Southeast Norway (2.9 million inhabitants). METHODS: All cases International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) coded as SLE during 2000-2017 were individually reviewed. Those with a confirmed SLE diagnosis by expert clinical assessment were included in the Nor-SLE cohort. Core clinical data were recorded, and the cases were classified according to 2019 EULAR/ACR and 1997 ACR criteria. Juvenile SLE was defined as <16 years at diagnosis and adult SLE was defined as ≥16 years at diagnosis. RESULTS: We included 737 incident SLE cases (701 adults, 36 juveniles). At diagnosis, 2019 EULAR/ACR criteria were more sensitive than 1997 ACR criteria for adults (91.6% vs 77.3%; p<0.001), but not for juveniles (97.2% vs 88.9%). The 2019 EULAR/ACR counts at diagnosis differed by age group and ethnicity, being higher in young cases and those originating from Asia. From time of diagnosis to study end the fulfilment rate of 2019 EULAR/ACR criteria for the adult cohort increased from 92.5% and 86.5% to 94.6% and 91.0%, respectively, for females and males (mean disease duration of 7.5 years). CONCLUSION: Showing 92% criteria fulfilment already at time of SLE diagnosis by 2019 EULAR/ACR criteria versus 77% by 1997 ACR criteria, the results from this population-based study suggest that the 2019 EULAR/ACR criteria will achieve its goal of capturing more early-SLE cases for clinical trials.
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Lupus Eritematoso Sistémico , Humanos , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/epidemiología , Noruega/epidemiología , Masculino , Femenino , Adulto , Adolescente , Incidencia , Persona de Mediana Edad , Adulto Joven , Estudios de Cohortes , Niño , Clasificación Internacional de Enfermedades , Vigilancia de la Población , Sensibilidad y EspecificidadRESUMEN
OBJECTIVE: To assess organ damage, with emphasis on the cardiovascular system, over the different stages of the disease in a large SLE cohort. METHODS: Multicentre, longitudinal study of a cohort of 4219 patients with SLE enrolled in the Spanish Society of Rheumatology Lupus Registry. Organ damage was ascertained using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). We longitudinally analysed SDI (globally and for each domain) over time only in the 1274 patients whose dates of damage events had been recorded. RESULTS: During the first year after diagnosis of SLE, 20% of the 1274 patients presented with new damage manifestations. At years 2 and 3, new damage was recorded in 11% and 9% of patients. The annual percentage of patients with new damage after year 5 decreased to 5%. In the first year with the disease, most damage was accumulated in the musculoskeletal, neuropsychiatric and renal systems; in later stages, most damage was in the musculoskeletal, ocular and cardiovascular systems. Considering 'cerebrovascular accident' and 'claudication for 6 months' as cardiovascular items, the cardiovascular system was the second most affected system during the early stages of SLE, with 19% of the patients who presented with damage affected at first year after diagnosis. During the late stages, 20-25% of the patients presenting with new damage did so in this modified cardiovascular domain of the SDI. CONCLUSIONS: New damage occurs mainly during the first year following diagnosis of SLE. Cardiovascular damage is relevant in both the early and the late stages of the disease. Strategies to prevent cardiovascular damage should be implemented early after diagnosis of SLE.
Asunto(s)
Sistema Cardiovascular , Lupus Eritematoso Sistémico , Sistema de Registros , Humanos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/epidemiología , Estudios Longitudinales , Masculino , Femenino , Adulto , España/epidemiología , Persona de Mediana Edad , Sistema Cardiovascular/fisiopatología , Enfermedades Cardiovasculares/epidemiología , Índice de Severidad de la Enfermedad , Progresión de la Enfermedad , ReumatologíaRESUMEN
OBJECTIVES: Contraception is crucial for safely timing pregnancies in patients with SLE. This study investigated predictors of contraception documentation in patients with SLE, and the alignment of contraception practices with the 2020 American College of Rheumatology (ACR) guidelines, within the Rheumatology Informatics System for Effectiveness (RISE) registry. MATERIALS AND METHODS: Female patients (aged 18-44 years) with SLE were identified via International Classification of Diseases (ICD)-9/ICD-10 coding within the RISE registry, which includes data from rheumatology clinics across the USA. Eligible patients were required to have ≥1 clinical visit in 2019 (prepandemic) or between 1 April 2020 and 30 March 2021 (mid-pandemic). Adjusted multilevel logistic modelling assessed patient, provider and practice characteristics for associations with contraception documentation. Contraception patterns were identified and compared with the 2020 ACR guidelines. RESULTS: Contraception documentation rates were similar in the prepandemic and mid-pandemic groups (8.1% and 8.5%, respectively). Higher documentation rates were found in women who were younger, White, and had more visits, as well as those seen within a health system, by a female provider, and within specific regions and electronic health record (EHR) systems. Prescription of a teratogenic medication did not influence contraception documentation or type. Oestrogen-containing contraceptives were prescribed less often to women at high risk for thrombosis (26.2% with thrombotic risk vs 60.6% without, p<0.0001) and history of lupus nephritis (LN) (53.8% with history of LN vs 63.2% without, p=0.024). CONCLUSIONS: Practices participating in the RISE registry do not currently record contraception in the large majority of women with SLE, although increased documentation in some EHRs suggests that system changes may improve rates of documentation. Women at higher risk for thrombosis were less likely to receive oestrogen, suggesting that warnings against oestrogen use has impacted contraception prescription, although the limited documentation and limited contraception among women taking teratogenic medications suggest a high unmet need.