HOPKINS LUPUS COHORT: 1999 Update

Antiphospholipid syndrome(APS) is an autoimmune disorder characterized clinically by vascular thrombosis and/or pregnancy morbidity, associated with persistently elevated titers of antiphospholipid antibodies on at least two measurements over 12 weeks apart. In this study, we conducted a systematic review of the literature utilizing the Pubmed platform, in order to acquire clinical information about acute coronary syndromes in patients with APS. The obtained articles were reviewed in order to register the clinical characteristics, the rate of occurrence, the prognosis and the therapeutic approach of these patients. APS should be considered in young patients with acute myocardial infarction, even in patients with normal coronary arteries. The pharmaceutical approach is mainly based on the vitamin K antagonists, and in certain occasions aspirin, without any definite guidelines on the subject. Further randomized clinical trials are imperative for a better understanding of the particular characteristics of this group of patients, so that a more complete therapeutic approach to be obtained.

Systemic lupus erythematosus (SLE) represents an autoimmune disease in which activation of the type I interferon pathway leads to dysregulation of tolerance and the generation of autoantibodies directed against nuclear constituents. The mechanisms driving the activation of the interferon pathway in SLE have been the subject of intense investigation but are still incompletely understood. Transposable elements represent an enormous source of RNA that could potentially stimulate the cell intrinsic RNA-recognition pathway, leading to upregulation of interferons. We used RNA-seq to define transposable element families and subfamilies in three cell types in SLE and found diverse effects on transposable element expression in the three cell types and even within a given family of transposable elements. When potential mechanisms were examined, we found that Hsp90 inhibition could drive increased expression of multiple type of transposable elements. Both direct inhibition and the delivery of a heat shock itself, which redirects heat shock regulators (including Hsp90) off of basal expression promoters and onto heat shock-responsive promoters, led to increased transposable element expression. This effect was amplified by the concurrent delivery of a histone deacetylase inhibitor. We conclude that transposable elements are dysregulated in SLE and there are tissue-specific effects and locus-specific effects. The magnitude of RNAs attributable to transposable elements makes their dysregulation of critical interest in SLE where transposable element RNA complexed with proteins has been shown to drive interferon expression.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of unknown etiology, characterized by the production of autoantibodies by autoreactive B cells, which are capable of inducing inflammatory changes in various organs and systems by several mechanisms. In patients with SLE, all the cardiac structures can be involved. Pericarditis is the most common cardiac abnormality, but lesions of the valves, myocardium, and coronary vessels may also occur. Nowadays, cardiac manifestations can be frequently recognized by echocardiography and other noninvasive tests, such as cardiac computed tomography or cardiac magnetic resonance imaging. Echocardiography is a nonexpensive, sensitive, and specific technique in detecting cardiac abnormalities, particularly mild pericarditis, valvular lesions, and myocardial dysfunction. Premature atherosclerosis is the most frequent cause of coronary artery disease in SLE patients. Efforts should be made to control traditional risk factors as well as all other factors, which could contribute to atherosclerotic plaque development.

Los registros de pacientes son herramientas útiles para evaluar enfermedades poco frecuentes. Nuestro objetivo es presentar el «Registro español de pacientes con lupus eritematoso sistémico» (RELES).

RELES se inició en 2008, como un registro multicéntrico de cohortes, observacional, prospectivo, incluyendo a pacientes desde el momento del diagnóstico, cuyo objetivo es analizar la incidencia y complicaciones no inflamatorias del lupus eritematoso sistémico (LES). Participan los servicios de Medicina Interna de 38 hospitales españoles.

Se incluyó a 298 pacientes con una edad media de 40,8 ± 15,7 años, de los que el 88,9% eran mujeres y el 85,6% de raza caucásica. En la primera visita, predominaron las manifestaciones articulares (74,5%). Ciento setenta y siete pacientes (59,4%) mostraban positividad para anti-DNA nativo, siendo superior en estos la frecuencia de nefritis lúpica (26,7% vs. 14%, p = 0,009; riesgo relativo [RR] 1,33), de anemia hemolítica (13,6% vs. 4,1%, p= 0,07; RR 1,46) y linfopenia (55,4% vs. 43,8%, p = 0,05; RR 1,21). La mediana del Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI 2K) fue de 9,64 puntos (rango intercuartílico 4-13). Los tratados con antipalúdicos antes del diagnóstico de LES tenían una mediana de SLEDAI en la primera visita de 5, frente a 8 en los que no los tomaban (p = 0,02).

RELES constituye la primera cohorte de pacientes con LES recogidos desde el momento del diagnóstico en España. La presencia de anti-DNA se ha relacionado con manifestaciones graves como nefritis y anemia hemolítica. El tratamiento con antipalúdicos antes del diagnóstico se asoció con una enfermedad menos activa al comienzo.

Patient registries are useful tools for assessing rare diseases. Our objective is to present the Spanish registry of patients with systemic lupus erythematosus (Registro español de pacientes con lupus eritematoso sistémico, RELES).

RELES was started in 2008 as an observational, prospective, multicentre cohort registry that included patients from the time they were diagnosed. The registry's objective is to analyse the incidence and noninflammatory complications of systemic lupus erythematosus (SLE). The departments of internal medicine of 38 Spanish hospitals participate in this registry.

A total of 298 patients with a mean age of 40.8 ± 15.7 years were included, 88.9% of whom were women and 85.6% of whom were white. In the first visit, there was a predominance of joint manifestations (74.5%). One hundred and seventy-seven patients (59.4%) were positive for anti-native DNA. In these patients, there was a higher rate of lupus nephritis (26.7% vs. 14%, p=.009; relative risk [RR], 1.33), haemolytic anaemia (13.6% vs. 4.1%, p=.07; RR, 1.46) and lymphopenia (55.4% vs. 43.8%, p=.05; RR, 1.21). The median Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI 2 K) score was 9.64 points (interquartile range, 4-13). The patients treated with antimalarial drugs before the diagnosis of SLE had a median SLEDAI score in the first visit of 5, compared with 8 for those who were not treated with these drugs (p=.02).

RELES constitutes the first Spanish patient cohort with SLE recorded from the time of the diagnosis. The presence of anti-DNA has been related to severe manifestations such as nephritis and haemolytic anaemia. Treatment with antimalarial drugs before the diagnosis was associated with less active disease at the initial presentation.

El lupus eritematoso sistémico es una enfermedad autoinmune, multisistémica de etiología desconocida, que afecta principalmente a mujeres en edad reproductiva. Dentro de las manifestaciones más frecuentes se encuentran los compromisos renal e inmunológico; el primero es el responsable de gran parte de la morbimortalidad de los pacientes y el segundo está fuertemente asociado a múltiples manifestaciones clínicas.

Analizar la prevalencia y características de las principales manifestaciones clínicas e inmunológicas de 115 pacientes con diagnóstico de lupus eritematoso sistémico del Hospital Universitario San Vicente Fundación y establecer la asociación entre los anticuerpos específicos y el compromiso de órgano.

Los pacientes fueron vistos por el Grupo de Reumatología de la Universidad de Antioquia entre 2008 y 2012. Los datos clínicos e inmunológicos se recolectaron del archivo o sistema electrónico de historias clínicas del hospital, en un formato previamente protocolizado.

Similar a lo informado por otros estudios, se encontró asociación entre hipocomplementemia y compromiso renal, y mayor alteración de las pruebas de función renal como creatinina, nitrógeno ureico en sangre, depuración de creatinina y proteinuria en 24 h. La frecuencia de anticuerpos anti-ADN de doble cadena fue del 79,1% y estos se encontraron asociados con compromiso renal y puntuaciones más altas de «Systemic Lupus Erythematosus Disease Activity Index». Se observó también asociación entre anticuerpos anti-Sm con serositis y lupus discoide.

Systemic lupus erythematosus is an autoimmune disease. The etiology is unknown, and it primarily affects women of reproductive age. Among the most common manifestations are the renal and immune system involvement; the first one is responsible for the majority of the morbidity and mortality of patients, and the second strongly associated with multiple clinical manifestations.

To analyze the prevalence and characteristics of the main clinical and immunological manifestations of 115 patients diagnosed with systemic lupus erythematosus in the Hospital Universitario San Vicente Fundación, and to determine the association between autoantibodies and organ involvement.

Patients were seen by the Rheumatology Group, University of Antioquia, between 2008 and 2012. Clinical and immunological data were collected from the files or electronic medical records using a previously designed format.

The study found an association between hypocomplementemia and renal involvement, similar to other studies. Nephritis was found in patients with active lupus, as well as a greater impairment of renal function tests such as, creatinine, blood urea nitrogen, creatinine clearance, and proteinuria. The percentage of patients with anti-dsDNA was 79.1%, and these antibodies were associated with renal involvement, as well as higher Systemic Lupus Erythematosus Disease Activity Index scores; anti-Sm antibodies was associated with serositis and discoid lupus.