Citrullination facilitates cross-reactivity of rheumatoid factor with non-IgG1 Fc epitopes in rheumatoid arthritis

Rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPAs) are the two most prevalent autoantibodies in rheumatoid arthritis (RA), and are thought to have distinct autoantigen targets. Whilst RF targets the Fc region of antibodies, ACPAs target a far broader spectrum of citrullinated peptides. Here we demonstrate significant sequence and structural homology between proposed RF target epitopes in IgG1 Fc and the ACPA target fibrinogen. Two of the three homologous sequences were susceptible to citrullination, and this modification, which occurs extensively in RA, permitted significant cross-reactivity of RF+ patient sera with fibrinogen in both western blots and ELISAs. Crucially, this reactivity was specific to RF as it was absent in RF− patient and healthy control sera, and could be inhibited by pre-incubation with IgG1 Fc. These studies establish fibrinogen as a common target for both RF and ACPAs, and suggest a new mechanism in RF-mediated autoimmune diseases wherein RF may act as a precursor from which the ACPA response evolves

Efficacy and adverse effects of intravenous lignocaine therapy in fibromyalgia syndrome

BACKGROUND: To investigate the effects of intravenous lignocaine infusions (IV lignocaine) in fibromyalgia. METHODS: Prospective study of the adverse effects of IV lignocaine in 106 patients with fibromyalgia; retrospective questionnaire study of the efficacy of IV lignocaine in 50 patients with fibromyalgia. RESULTS: Prospective study: Two major (pulmonary oedema and supraventricular tachycardia) and 42 minor side-effects were reported. None had long-term sequelae. The commonest was hypotension (17 cases). Retrospective study: Pain and a range of psychosocial measures (on single 11-point scales) improved significantly after treatment. There was no effect of the treatment on work status. The average duration of pain relief after the 6-day course of treatment was 11.5 ± 6.5 weeks. CONCLUSIONS: Intravenous lignocaine appears to be both safe and of benefit in improving pain and quality of life for patients with fibromyalgia. This needs to be confirmed in prospective randomised controlled trials

A patient with hypereosinophilic syndrome that manifested with acquired hemophilia and elevated IgG4: a case report

<p>Abstract</p> <p>Introduction</p> <p>Hypereosinophilic syndrome is defined as a prolonged state (more than six months) of eosinophilia (greater than 1500 cells/μL), without an apparent etiology and with end-organ damage. Hypereosinophilic syndrome can cause coagulation abnormalities. Among hypereosinophilic syndrome types, the lymphocytic variant (lymphocytic hypereosinophilic syndrome) is derived from a monoclonal proliferation of T lymphocytes. Here, we describe the case of a patient with lymphocytic hypereosinophilic syndrome who presented with a coagulation abnormality. To the best of our knowledge, this is the first such report including a detailed clinical picture and temporal cytokine profile.</p> <p>Case presentation</p> <p>A 77-year-old Japanese man presented to our facility with massive hematuria and hypereosinophilia (greater than 2600 cells/μl). His eosinophilia first appeared five years earlier when he developed femoral artery occlusion. He manifested with multiple hematomas and prolonged activated partial thromboplastin time. His IgG4 level was remarkably elevated (greater than 2000 mg/dL). Polymerase chain reaction tests of peripheral blood and bone marrow identified lymphocytic hypereosinophilic syndrome. His prolonged activated partial thromboplastin time was found to be due to acquired hemophilia. Glucocorticoids suppressed both the hypereosinophilia and coagulation abnormality. However, tapering of glucocorticoids led to a relapse of the coagulation abnormality alone, without eosinophilia. Tumor necrosis factor α, interleukin-5, and/or eotaxin-3 may have caused the hypereosinophilia, and interleukin-10 was correlated with the coagulation abnormality.</p> <p>Conclusions</p> <p>To the best of our knowledge, this is the first case in which lymphocytic hypereosinophilic syndrome and IgG4-related disease have overlapped. In addition, our patient is only the second case of hypereosinophilic disease that manifested with acquired hemophilia. Our patient relapsed with the coagulation abnormality alone, without eosinophilia. This report shows that the link between eosinophilia, IgG4, and clinical manifestations is not simple and provides useful insight into the immunopathology of hypereosinophilic syndrome and IgG4-related disease.</p

Impact of Rituximab on Immunoglobulin Concentrations and B Cell Numbers after Cyclophosphamide Treatment in Patients with ANCA-Associated Vasculitides

OBJECTIVE: To assess the impact of immunosuppressive therapy with cyclophosphamide (CYC) and rituximab (RTX) on serum immunoglobulin (Ig) concentrations and B lymphocyte counts in patients with ANCA-associated vasculitides (AAVs). METHODS: Retrospective analysis of Ig concentrations and peripheral B cell counts in 55 AAV patients. RESULTS: CYC treatment resulted in a decrease in Ig levels (median; interquartile range IQR) from IgG 12.8 g/L (8.15-15.45) to 9.17 g/L (8.04-9.90) (p = 0.002), IgM 1.05 g/L (0.70-1.41) to 0.83 g/L (0.60-1.17) (p = 0.046) and IgA 2.58 g/L (1.71-3.48) to 1.58 g/L (1-31-2.39) (p = 0.056) at a median follow-up time of 4 months. IgG remained significantly below the initial value at 14.5 months and 30 months analyses. Subsequent RTX treatment in patients that had previously received CYC resulted in a further decline in Ig levels from pre RTX IgG 9.84 g/L (8.71-11.60) to 7.11 g/L (5.75-8.77; p = 0.007), from pre RTX IgM 0.84 g/L (0.63-1.18) to 0.35 g/L (0.23-0.48; p<0.001) and from pre RTX IgA 2.03 g/L (1.37-2.50) to IgA 1.62 g/L (IQR 0.84-2.43; p = 0.365) 14 months after RTX. Treatment with RTX induced a complete depletion of B cells in all patients. After a median observation time of 20 months median B lymphocyte counts remained severely suppressed (4 B-cells/µl, 1.25-9.5, p<0.001). Seven patients (21%) that had been treated with CYC followed by RTX were started on Ig replacement because of severe bronchopulmonary infections and serum IgG concentrations below 5 g/L. CONCLUSIONS: In patients with AAVs, treatment with CYC leads to a decline in immunoglobulin concentrations. A subsequent RTX therapy aggravates the decline in serum immunoglobulin concentrations and results in a profoundly delayed B cell repopulation. Surveying patients with AAVs post CYC and RTX treatment for serum immunoglobulin concentrations and persisting hypogammaglobulinemia is warranted

Diseño de un manual de detección de ansiedad social en adolescentes

Curso de Especial InterésEl objetivo de este trabajo de grado ha sido diseñar un manual dirigido a padres y docentes, en el que se establezcan técnicas de detección de ansiedad social en adolescentes; el diseño de este manual permite un aprendizaje significativo de una forma diferente, en un lenguaje claro y preciso, en formato digital para un fácil acceso y portabilidad del material, logrando de esta forma, que la población adolescente sea beneficiada a través de las acciones que se emprenderán por parte de los padres de familia, docentes y profesionales.142 p.RESUMEN 1. JUSTIFICACIÓN 2. OBJETIVOS 3. ESTUDIO DEL MERCADO 4. PRESENTACIÓN DEL PRODUCTO 5. CLIENTES – SEGMENTACIÓN 6. COMPETENCIA 7. CANALES DE DISTRIBUCIÓN 8. RESULTADOS DEL ESTUDIO DE MERCADO 9. DISCUSIÓN DEL ESTUDIO DE MERCADO 10. PRESUPUESTO 11. RESULTADOS 12. CONCLUSIONES REFERENCIAS APÉNDICESPregradoPsicólog

Echocardiography may help detect pulmonary vasculopathy in the early stages of pulmonary artery hypertension associated with systemic sclerosis

<p>Abstract</p> <p>Background</p> <p>Pulmonary arterial hypertension (PAH) in patients with systemic sclerosis is associated with a poor prognosis, but this can be improved by early disease detection. Abnormal pulmonary and cardiac function can be detected early by means of echocardiography, whereas right heart catheterization is usually performed later.</p> <p>Objectives</p> <p>The purpose of this prospective study was to detect early the presence of pulmonary artery vasculopathy in patients with verified systemic sclerosis without significant pulmonary fibrosis, normal lung volumes and a mildly reduced lung diffusion capacity of carbon monoxide (DLCO).</p> <p>Methods</p> <p>Nineteen consecutive female NYHA class I-II patients with scleroderma and a PAPs of < 35 mm/Hg measured by echocardiography, were enrolled between September 2007 and September 2009. They had a mean age of 51 ± 13 years, body mass index of 25 ± 5 kg/m²). They all underwent complete Doppler echocardiography, CPET, a pulmonary ventilation test (carbon monoxide lung diffusion, DLCO), HRCT. To investigate PAH by means of complete resting Doppler echocardiography estimates of systolic pulmonary artery pressure (PAPs) derived from tr icuspid regurgitation, mean PAP derived from pulmonary regurgitation, pulmonary vessel resistance (PVR) derived from the acceleration time of the pulmonary outflow tract (ACTpo), and right ventricular function derived from tricuspid annular plane systolic excursion (TAPSE). Right heart catheterisation was conducted only, if pulmonary hypertension was suggested by echocardiography and an abnormal ventilator test.</p> <p>The data are given as mean values ± SD, unless otherwise stated. The correlations between the variables were analysed using Pearson's <it>r </it>coefficient, and the predictive value of the variables was calculated using linear regression analysis. A p value of > 0.05 was considered significant.</p> <p>Results</p> <p>Right heart catheterization detected PAH in 15/19 patients; mean PAP was 30.5 mm/Hg and RVP 3.6 UW. Coronary angiography of the patients aged more than 55 years showed some evidence of significant coronary artery disease. Echocardiography showed high systolic PAP values (46 ± 8 mmHg), whereas right ventricular function was normal (TAPSE 23 ± 3 mm), and in line with the NYHA class. ACTpo was reduced in the patients with a systolic PAP of < 46 mm/Hg (p > 0.001) and positively correlated with DLCO (p > 0.001) and the hemodynamic data.</p> <p>There was a good correlation between ACTpo and PVR (hemodynamic data) (r = -0615; p > 0.01).</p> <p>Conclusions</p> <p>Although they need to be confirmed by studies of larger series of patients, our findings suggest that, in comparison with hemodynamic data, non-invasive echocardiographic measurements are an excellent means of identifying early-stage PAH.</p