Is there a common genetic basis for autoimmune diseases?

Autoimmune diseases (ADs) represent a diverse collection of diseases in terms of their demographic profile and primary clinical manifestations. The commonality between them however, is the damage to tissues and organs that arises from the response to self-antigens. The presence of shared pathophysiological mechanisms within ADs has stimulated searches for common genetic roots to these diseases. Two approaches have been undertaken to sustain the “common genetic origin” theory of ADs. Firstly, a clinical genetic analysis showed that autoimmunity aggregates within families of probands diagnosed with primary Sjögren's (pSS) syndrome or type 1 diabetes mellitus (T1D). A literature review supported the establishment of a familiar cluster of ADs depending upon the proband's disease phenotype. Secondly, in a same and well-defined population, a large genetic association study indicated that a number of polymorphic genes (i.e. HLA-DRB1, TNF and PTPN22) influence the susceptibility for acquiring different ADs. Likewise, association and linkage studies in different populations have revealed that several susceptibility loci overlap in ADs, and clinical studies have shown that frequent clustering of several ADs occurs. Thus, the genetic factors for ADs consist of two types: those which are common to many ADs (acting in epistatic pleitropy) and those that are specific to a given disorder. Their identification and functional characterization will allow us to predict their effect as well as to indicate potential new therapeutic interventions. Both autoimmunity family history and the co-occurrence of ADs in affected probands should be considered when performing genetic association and linkage studies.

What are the priorities for prevention and control of non-communicable diseases and injuries in sub-Saharan Africa and South East Asia?

Last year’s UN high level meeting sought to galvanise the international community into scaling up its response to the escalating global burden of non-communicable diseases. With resources tight, D Chisholm and colleagues examine which interventions should be given priority for action and investment

Should rituximab be considered as the first-choice treatment for severe autoimmune rheumatic diseases?

The present study aimed to assess the tolerance and efficacy of rituximab (RTX), a chimeric IgG1 monoclonal antibody directed against the CD20 receptor present in B lymphocytes, in patients with autoimmune rheumatic diseases (AIRD). For this purpose, patients treated with RTX and their respective clinical charts were comprehensively examined. Indications for treatment were a refractory character of the disease, inefficacy or intolerance of other immunosuppressors. Activity indexes (SLEDAI, DAS28, and specific clinical manifestations) were used to evaluate efficacy. Serious side effects were also recorded. Seventy-four patients were included. Forty-three patients had systemic lupus erythematosus (SLE), 21 had rheumatoid arthritis (RA), 8 had Sjögren’s syndrome (SS), and 2 had Takayasu’s arteritis (TA). RTX was well-tolerated in 66 (89%) patients. In 8 patients (SLE = 3, SS = 3, RA = 2), serious side effects lead to discontinuation. The mean follow-up period was 12 ± 7.8 (2–35) months. The efficacy of RTX was registered in 58/66 (87%) patients, of whom 36 (83%) had SLE, 18/21 (85%) had RA, 3/8 (37%) had SS, and 1 had TA. The mean time of efficacy was 6.3 ± 5.1 weeks. A significant steroid-sparing effect was noticed in half of the patients. These results add further evidence for the use of RTX in AIRD. Based on its risk–benefit ratio, RTX might be used as the first-choice treatment for patients with severe AIRD.

Organic solvents as risk factor for autoimmune diseases: a systematic review and meta-analysis

Background: Genetic and epigenetic factors interacting with the environment over time are the main causes of complex diseases such as autoimmune diseases (ADs). Among the environmental factors are organic solvents (OSs), which are chemical compounds used routinely in commercial industries. Since controversy exists over whether ADs are caused by OSs, a systematic review and meta-analysis were performed to assess the association between OSs and ADs. Methods and Findings: The systematic search was done in the PubMed, SCOPUS, SciELO and LILACS databases up to February 2012. Any type of study that used accepted classification criteria for ADs and had information about exposure to OSs was selected. Out of a total of 103 articles retrieved, 33 were finally included in the meta-analysis. The final odds ratios (ORs) and 95% confidence intervals (CIs) were obtained by the random effect model. A sensitivity analysis confirmed results were not sensitive to restrictions on the data included. Publication bias was trivial. Exposure to OSs was associated to systemic sclerosis, primary systemic vasculitis and multiple sclerosis individually and also to all the ADs evaluated and taken together as a single trait (OR: 1.54; 95% CI: 1.25-1.92; p-value, 0.001). Conclusion: Exposure to OSs is a risk factor for developing ADs. As a corollary, individuals with non-modifiable risk factors (i.e., familial autoimmunity or carrying genetic factors) should avoid any exposure to OSs in order to avoid increasing their risk of ADs.

How do autoimmune diseases cluster in families? A systematic review and meta-analysis

Background: A primary characteristic of complex genetic diseases is that affected individuals tend to cluster in families (that is, familial aggregation). Aggregation of the same autoimmune condition, also referred to as familial autoimmune disease, has been extensively evaluated. However, aggregation of diverse autoimmune diseases, also known as familial autoimmunity, has been overlooked. Therefore, a systematic review and meta-analysis were performed aimed at gathering evidence about this topic. Methods: Familial autoimmunity was investigated in five major autoimmune diseases, namely, rheumatoid arthritis, systemic lupus erythematosus, autoimmune thyroid disease, multiple sclerosis and type 1 diabetes mellitus. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed. Articles were searched in Pubmed and Embase databases. Results: Out of a total of 61 articles, 44 were selected for final analysis. Familial autoimmunity was found in all the autoimmune diseases investigated. Aggregation of autoimmune thyroid disease, followed by systemic lupus erythematosus and rheumatoid arthritis, was the most encountered. Conclusions: Familial autoimmunity is a frequently seen condition. Further study of familial autoimmunity will help to decipher the common mechanisms of autoimmunity.

Plasmapheresis vs. immunoglobulin in autoimmune neurologic diseases: a meta-analysis

Objectives: to evaluate the efficacy and safety of human immunoglobulin versus plasmapheresis in the management of autoimmune neurologic diseases. Likewise, length of hospital stay and duration of ventilator support were compared. Methods: Randomized controlled trials and analytical observational studies of more than 10 cases, were reviewed. Cochrane Neuromuscular Disease Group trials, MEDLINE, EMBASE, HINARI Ovid, the Database of abstracts of reviews of effectiveness and the Economic evaluation Database were searched as data source. Reference lists were examined for further relevant articles. A random-effect model was used to derive a pooled risk ratio. Results: 725 articles were found and 27 met the criteria for a population studied of 4717 cases: 14 articles were about Guillain Barré syndrome, 10 of Myasthenia Gravis, one of Sydenham Chorea, one of Chronic inflammatory demyelinating polyneuropathy, and one of PANDAS. No evidence was found in favor of any of the two treatments as regards effectiveness (OR 0.94, IC 0.63 – 1.41, p= 0.77) or ventilator support time; IGIV had a significant better safety profile than plasmapheresis (OR 0.70, IC 0.51 – 0.96, p= 0.03) and patients needed less time of hospital stay (p=0.03). Conclusions: There is no evidence for superiority in the effectiveness of immunoglobulin or plasmapheresis in the management of autoimmune neurologic diseases. Nevertheless, patients treated with immunoglobulin have statistically significant less adverse effects, a shorter hospital stay and a tendency of less ventilator support time. These premises could lead to fewer costs for health services but an economic study should be done.

Riesgo de hipertensión arterial por ruido laboral: revisión sistemática

Introducción: la pérdida auditiva inducida por ruido es el efecto nocivo del ruido más comúnmente estudiado, sin embargo, el ruido también produce trastornos digestivos y del sueño, cambios en los niveles de cortisol, efectos cardiovasculares e hipertensión arterial (HTA), entre otros. Objetivo: determinar si la exposición laboral a ruido induce hipertensión arterial. Materiales y métodos: se siguieron las recomendaciones del método PRISMA para revisiones sistemáticas. Se hizo una búsqueda de estudios en PUBMED utilizando los términos “occupational and noise and hypertension” y aplicando los filtros: 1) publicaciones incluidas entre 2005-2015; 2) estudios publicados en inglés; 3) revisión de títulos y resúmenes; 4) revisión completa de los textos para un total final de 32 estudios. Se hizo la revisión, análisis y resumen de todos los estudios. Resultados: los estudios concluyeron que aquellos portadores de los polimorfismos de la enzima convertidora de angiotensina expuestos a ruido, tuvieron una mayor susceptibilidad genética a tener HTA. Los estudios reportaron una asociación positiva entre ruido e HTA. Hay controversia acerca de la relación que existe entre HTA, ruido y coexposición a otros factores como calor, trabajo por turnos, presencia de solventes o plomo en el lugar de trabajo y carga física. Conclusiones: Se presume que solo los niveles de ruido ≥ 85 dBA tienen efectos negativos sobre la salud, pero se ha encontrado que los efectos no auditivos del ruido se producen por debajo de este parámetro. Recomendaciones: se sugiere el uso de la pérdida auditiva inducida por ruido entre población trabajadora como un método de tamizaje para detectar personas prehipertensas, con el fin prevenir la generación de HTA.

Pulsioximetría de pacientes en hemodiálisis, de la unidad de terapia renal – fundación cardioinfantil, análisis para establecer recomendaciones

Introducción. En Colombia, el 80% de los pacientes con enfermedad renal crónica en hemodiálisis tienen fístula arteriovenosa periférica (FAV) que asegura el flujo de sangre durante la hemodiálisis (1), la variabilidad en el flujo de sangre en el brazo de la FAV hacia la parte distal, puede afectar la lectura de la oximetría de pulso (SpO2) (2), llevando a la toma de decisiones equivocadas por el personal de salud. El objetivo de este estudio es aclarar si existe diferencia entre la SpO2 del brazo de la FAV y el brazo contralateral. Materiales y métodos. Se realizó un estudio de correlación entre los valores de SpO2 del brazo con FAV contra el brazo sin FAV, de 40 pacientes que asistieron a hemodiálisis. La recolección de los datos se llevó a cabo, con un formato que incluyó el resultado de la pulsioximetria y variables asociadas, antes, durante y después de la hemodiálisis. Se comparó la mediana de los deltas de las diferencias con pruebas estadísticas T Student – Mann Whitney, aceptando un valor significativo de p < 0,05. Resultados. No se encontraron diferencias estadísticamente significativas de la SpO2 entre el brazo con FAV y el brazo sin FAV, antes, durante y después de la diálisis, sin embargo si se apreció una correlación positiva estadísticamente significativa. Conclusiones. Se encontró correlación positiva estadísticamente significativa, donde no hubo diferencias en el resultado la pulsioximetría entre el brazo con FAV y brazo sin FAV, por lo tanto es válido tomar la pulsioximetría en cualquiera de los brazos.

Characterization and efficacy of bacterial strains for biological control of soil-borne diseases caused by Phytophthora cactorum and Meloidogyne javanica on Rosaceous plants

S'avaluaren 58 soques de Pseudomonas fluorescens i Pantoea agglomerans per la seva eficàcia en el biocontrol de la malaltia causada per l'oomicet Phytophthora cactorum en maduixera i pel nematode formador de gal·les Meloidogyne javanica en el portaempelt GF-677. Es desenvolupà un mètode ex vivo d'inoculació de fulla amb l'objectiu de seleccionar soques bacterianes com a agents de control biològic de P. cactorum en maduixera. Tres soques de P. fluorescens es seleccionaren com a soques eficaces en el biocontrol del patogen en fulles i en la reducció de la malaltia en plantes de maduixera. La combinació de soques semblà millorar la consistència del biocontrol en comparació amb les soques aplicades individualment. Tres soques de P. fluorescens es seleccionaren per la seva eficàcia en la reducció de la infecció de M. javanica en portaempelts GF-677. La combinació d'aquestes soques no incrementà l'eficàcia del biocontrol, però semblà reduir la seva variabilitat.