Serum Endoglin Levels in Patients Suffering from Systemic Sclerosis and Elevated Systolic Pulmonary Arterial Pressure

Background. Pulmonary arterial hypertension (PAH) is the main cause of morbimortality in systemic sclerosis (SSc). Increased Eng expression has been demonstrated in SSc patients. Objective. Ascertaining serum levels of Eng in SSc patients with and without elevated systolic pulmonary arterial pressure (sPAP) and comparing them with that of healthy volunteers. Methods. A cross-sectional study was carried out. A commercial ELISA kit was used for measuring serum concentrations of Eng in 60 subjects: 40 patients with SSc with and without elevated sPAP, compared to 20 healthy control subjects. Elevated sPAP was detected by echocardiogram. Results. No association between positive Eng and elevated sPAP was found when compared to the SSc without elevated sPAP group (OR = 2.85; 0.65–12.88 95% CI; P = .11); however, an association was found between positive Eng and elevated sPAP compared to healthy controls (OR = 23.22; 2.46–1050.33 95% CI; P = .001), and weak association was found between the positive Eng with SSc without elevated sPAP group compared to healthy controls (OR = 8.14, 0.8–393.74 95% CI; P = .046). Conclusion. Raised serum levels of Eng in SSc patients compared to healthy controls were found, suggesting a role for Eng in SSc vasculopathy and not just in elevated sPAP. However, prospective studies are needed to verify such observations

Gastric Antral Vascular Ectasia in Systemic Sclerosis: Current Concepts

Introduction. Gastric antral vascular ectasia (GAVE) is a rare entity with unique endoscopic appearance described as “watermelon stomach.” It has been associated with systemic sclerosis but the pathophysiological changes leading to GAVE have not been explained and still remain uncertain. Methods. Databases Medline, Scopus, Embase, PubMed, and Cochrane were searched for relevant papers. The main search words were “Gastric antral vascular ectasia,” “Watermelon Stomach,” “GAVE,” “Scleroderma,” and “Systemic Sclerosis.” Fifty-four papers were considered for this review. Results. GAVE is a rare entity in the spectrum of manifestations of systemic sclerosis with unknown pathogenesis. Most patients with systemic sclerosis and GAVE present with asymptomatic anemia, iron deficiency anemia, or heavy acute gastrointestinal bleeding. Symptomatic therapy and endoscopic ablation are the first-line of treatment. Surgical approach may be recommended for patients who do not respond to medical or endoscopic therapies. Conclusion. GAVE can be properly diagnosed and treated. Early diagnosis is key in the management of GAVE because it makes symptomatic therapies and endoscopic approaches feasible. A high index of suspicion is critical. Future studies and a critical review of the current findings about GAVE are needed to understand the role of this condition in systemic sclerosis

Systemic sclerosis: A world wide global analysis

The objective of this study was to analyze epidemiological tendencies of systemic sclerosis (SSc) around the world in order to identify possible local variations in the presentation and occurrence of the disease. A systematic review of the literature was performed through electronic databases using the keywords 'Systemic Sclerosis' and 'Clinical Characteristics.' Out of a total of 167 articles, 41 were included in the analysis. Significant differences in the mean age at the time of diagnosis, subsets of SSc, clinical characteristics, and presence of antibodies were found between different regions of the word. Because variations in both additive and nonadditive genetic factors and the environmental variance are specific to the investigated population, ethnicity and geography are important characteristics to be considered in the study of SSc and other autoimmune diseases. © Clinical Rheumatology 2009

CARACTERIZACIÓN DE LOS PERFILES DE EXPRESIÓN DEL FACTOR DE TRANSCRIPCIÓN IKAROS EN ENFERMEDADES AUTOINMUNES

Introducción y objetivo: Las enfermedades autoinmunes son patologías complejas asociadas a distinos genes que no logran explicar completamente estos sindromes. Ikaros es un factor de transcripción linfoide con un alto nivel de splicing alternativo, de las cuales resultan distintas isoformas, entre ellas isoformas dominantes negativas. En este estudio caracterizamos el perfil de expresión de las isoformas de Ikaros en pacientes con síndrome de Sjögren, lupus eritematoso sistémico, esclerosis sistémica y artritis reumatoide. Métodos: Se extrajo RNA a partir de sangre periférica de 180 individuos, cada interexón se amplificó con un nuevo diseño de qRT-PCR y la detección de splicings no canónicos se realizó mediante el análisis de las curvas melting. Resultados: La expresión de Ikaros se encuentra alterada en enfermedades autoinmunes. Los niveles disminuidos del interexón IK4-5 en todas las patologías autoinmunes se asoció con la presencia de isoformas dominantes negativas. En los pacientes con artritis se observó la mayor expresión de Ikaros y en lupus la más baja, indicando en este caso que ésta podría ser una posible causa de la enfermedad. Las variantes de splicing detectadas afectan tanto los exones con dominios de unión al ADN y de dimerización con otras proteínas. Conclusión: Éste es el primer estudio en Latinoamérica que determina la relación entre Ikaros y enfermedades autoinmunes. Los diferentes perfiles de expresión en artritis y lupus permiten considerar a Ikaros como un biomarcador mediante el cual se puede diferenciar la enfermedad frente al resto

IKAROS expression profiles characterize different autoimmune diseases

Abstract Background Autoimmune diseases are syndromes characterized by an immune response against self-antigens. They are complex pathologies associated with a variety of genetic determinants, but these genes cannot fully explain the aetiology of autoimmune disorders. Ikaros is a transcription factor that plays a major role in lymphoid differentiation. Methods In this study, we characterized the expression profiles of Ikaros isoforms by quantifying the interexonic regions of patients diagnosed with Sjögren’s syndrome, systemic lupus erythaematosus, systemic sclerosis and rheumatoid arthritis in RNA extracted from peripheral blood. REST software was used for relative quantification and Hierarchical clustering analysis was performed using Cluster and TreeView. Results The expression of Ikaros was altered in all diseases examined. Significant differences were found in all of the interexonic regions between the comparison groups. Decreased expression of the IE3–4, 4–5 and 5–6 regions in all of the autoimmune pathologies was associated with the presence of dominant negative isoforms. Differences in the expression of several exons in rheumatoid arthritis and systemic lupus erythaematosus indicated the presence of different isoforms, which could serve as biomarkers for these diseases. Conclusion This study is the first conducted in Latinamerica that sought to determine the relationship between Ikaros and autoimmune diseases and is the first description of Ikaros in patients with rheumatoid arthritis, Sjögren’s syndrome and systemic sclerosis. Furthermore, we confirmed that Ikaros expression is altered in systemic lupus erythaematosus

Polyautoimmunity and familial autoimmunity in systemic sclerosis

Characterization of the extent to which particular combinations of autoimmune diseases occur in excess of that expected by chance may offer new insights into possible common pathophysiological mechanisms. The goal of this study was to investigate the spectrum of polyautoimmunity (i.e. autoimmune diseases co-occurring within patients) and familial autoimmunity (i.e. diverse autoimmune diseases co-occurring within families) in patients with systemic sclerosis (SSc). A cross-sectional study of two convenience samples of patients with SSc, one in Canada and the other in Colombia, was performed. History of other autoimmune diseases in the SSc patients as well as a family history of autoimmunity was obtained. Of 719 patients, 273 (38%) had at least one other autoimmune disease. A total of 366 autoimmune diseases were reported, of which the most frequent were autoimmune thyroid disease (AITD, 38%), rheumatoid arthritis (RA, 21%), Sjögren's syndrome (18%), and primary biliary cirrhosis (4%). There were 260 (36%) patients with first-degree relatives with at least one autoimmune disease, of which the most frequent were RA (18%) and AITD (9%). Having at least one first-degree relative with autoimmune disease was a significant predictor of polyautoimmunity in SSc patients. No significant differences in polyautoimmunity or familial autoimmunity were noted between diffuse and limited subsets of disease. Our results indicate that polyautoimmunity is frequent in patients with SSc and autoimmune diseases cluster within families of these patients. Clinically different autoimmune phenotypes might share common susceptibility variants, which acting in epistatic pleiotropy may represent risk factors for autoimmunity. © 2008 Elsevier Ltd. All rights reserved

Polyautoimmunity and familial autoimmunity in systemic sclerosis

"Characterization of the extent to which particular combinations of autoimmune diseases occur in excess of that expected by chance may offer new insights into possible common pathophysiological mechanisms. The goal of this study was to investigate the spectrum of polyautoimmunity (i.e. autoimmune diseases co-occurring within patients) and familial autoimmunity (i.e. diverse autoimmune diseases co-occurring within families) in patients with systemic sclerosis (SSc). A cross-sectional study of two convenience samples of patients with SSc, one in Canada and the other in Colombia, was performed. History of other autoimmune diseases in the SSc patients as well as a family history of autoimmunity was obtained. Of 719 patients, 273 (38%) had at least one other autoimmune disease. A total of 366 autoimmune diseases were reported, of which the most frequent were autoimmune thyroid disease (AITD, 38%), rheumatoid arthritis (RA, 21%), Sjögren's syndrome (18%), and primary biliary cirrhosis (4%). There were 260 (36%) patients with first-degree relatives with at least one autoimmune disease, of which the most frequent were RA (18%) and AITD (9%). Having at least one first-degree relative with autoimmune disease was a significant predictor of polyautoimmunity in SSc patients. No significant differences in polyautoimmunity or familial autoimmunity were noted between diffuse and limited subsets of disease. Our results indicate that polyautoimmunity is frequent in patients with SSc and autoimmune diseases cluster within families of these patients. Clinically different autoimmune phenotypes might share common susceptibility variants, which acting in epistatic pleiotropy may represent risk factors for autoimmunity. © 2008 Elsevier Ltd. All rights reserved.