Autoimmune-autoinflammatory rheumatoid arthritis overlaps: a rare but potentially important subgroup of diseases

At the population level, rheumatoid arthritis (RA) is generally viewed as autoimmune in nature with a small subgroup of cases having a palindromic form or systemic autoinflammatory disorder (SAID) phenotype. Herein, we describe resistant cases of classical autoantibody associated RA that had clinical, genetic and therapeutic responses indicative of coexistent autoinflammatory disease. Five patients with clinically overlapping features between RA and SAID including polysynovitis and autoantibody/shared epitope positivity, and who had abrupt severe self-limiting attacks including fevers and serositis, are described. Mutations or single nucleotide polymorphisms in recognised autoinflammatory pathways were evident. Generally, these cases responded poorly to conventional Disease-modifying anti-rheumatic drugs (DMARD) treatment with some excellent responses to colchicine or interleukin 1 pathway blockade. A subgroup of RA cases have a mixed autoimmune-autoinflammatory phenotype and genotype with therapeutic implications

IL-32: An Emerging Player in the Immune Response Network against Tuberculosis?

IL-32 has emerged as an important player in innate and adaptive immune responses. Kundu and Basu discuss a new study in PLoS Medicine that explored the role of IL-32 in the context of M. tuberculosis infection

Estudo nutricional de Schinus terebinthifolius (Raddi) em resposta à adubação potássica

The objective of this work was to evaluate the effect of K doses on the initial development and nutritional efficiency of Brazilian pepper tree. For this purpose it was developed under greenhouse conditions in pot experiment with five level of K2O (66.67, 133.33, 200, 266.67 and 333.33 mg kg-1) a randomized complete block design with five replicates. At 180 days after transplant, all plants were harvested and evaluated for height, diameter, leaf area, root and shoot dry mass, root and shoot contents, and efficiency of uptake, use and translocation of nutrients. Potassium fertilization increased the development of Brazilian pepper tree, the highest plant height and stem diameter were obtained when the plants were grown with 210 mg kg-1 K2O and the highest dry shoot mass, leaf area and nutrient content cultivating with the dose of 66,67 mg kg-1 de K2O.O objetivo deste trabalho foi avaliar o efeito de doses de K no desenvolvimento inicial e na eficiência nutricional de mudas da aroeirinha, em Latossolo Vermelho distroférrico. Um experimento em vasos foi conduzido em casa de vegetação na Universidade Federal da Grande Dourados, com os tratamentos constituídos de cinco doses de K2O (66,67, 133,33, 200, 266,67 e 333,33 mg kg-1), dispostos no delineamento experimental de blocos casualizados, com cinco repetições. As avaliações foram constituídas de medidas de altura, diâmetro, área foliar, massa seca de raiz e da parte aérea, conteúdo de nutrientes na planta, eficiência de absorção, uso e translocação de nutrientes. As plantas de aroeirinha apresentaram maior produção de massa seca da parte aérea, área foliar, relação parte aérea/raiz, conteúdo de nutriente parte aérea, eficiência de absorção, eficiência de uso de nutriente e eficiência de translocação na dose de 66,67 mg kg-1 de K2O, sendo a dose adequada para o crescimento inicial da aroeirinha

Desempenho de Leveduras Obtidas em Indústrias de Mato Grosso do Sul na Produção de Etanol em Mosto a Base de Cana de Açúcar

The process of ethanol production in Brazil uses sucrose as thesugar cane juice or molasses as a substrate for Saccharomyces cerevisiae whichresults in high production of ethanol. This study aims to evaluate thebiotechnological potential of strains of Saccharomyces cerevisiae used insugarcane mills in the southern region of Mato Grosso do Sul, the main power strain used in the region are: Catanduva 1, Pedra 2, Barra Grande 1and Fleischmann. Microbiological analysis showed similarities betweenaspects analyzed in the strains. The strains that showed the bestfermentation performance was Catanduva 1, strain Pedra 2 and Barra Grande1 showed the same response and the lower fermentation was showed inthe lineage Fleischmann. This study presented that the characterization ofthe potential of yeast strains in the fermentation process can increase ethanolproduction.O processo de produção de álcool combustível no Brasil utiliza a sacarose na forma de caldo de cana ou melaço como substrato para Saccharomyce cerevisiae o que resulta em alta produção de etanol. O presente trabalho tem como objetivo avaliar o potencial biotecnológico de linhagens de Saccharomyce cerevisiae utilizadas nas usinas sucroalcooleiras da região sul do estado de Mato Grosso do Sul. As principais linhagens utilizadas nas usinas da região são: Catanduva 1, Pedra 2, Barra Grande 1 e Fleischmann. As análises microbiológicas mostraram semelhanças entres os aspectos analisados nas linhagens. A linhagem que apresentou melhor performance fermentativa foi a Catanduva 1, as linhagens Pedra 2 e Barra Grande 1 apresentaram respostas semelhantes e a que apresentou menor fermentação foi a linhagem Fleischmann. Este estudo mostrou que a caracterização do potencial das linhagens de leveduras no processo fermentativo pode aumentar a produção de etanol

Autoantibodies against cytokines: phenocopies of primary immunodeficiencies?

Anti-cytokine autoantibodies may cause immunodeficiency and have been recently recognized as 'autoimmune phenocopies of primary immunodeficiencies' and are found in particular, but not exclusively in adult patients. By blocking the cytokine's biological function, patients with anti-cytokine autoantibodies may present with a similar clinical phenotype as the related inborn genetic disorders. So far, autoantibodies to interferon (IFN)-γ, GM-CSF, to a group of TH-17 cytokines and to IL-6 have been found to be causative or closely associated with susceptibility to infection. This review compares infectious diseases associated with anti-cytokine autoantibodies with primary immunodeficiencies affecting similar cytokines or related pathways

Biallelic JAK1 mutations in immunodeficient patient with mycobacterial infection

Mutations in genes encoding components of the immune system cause primary immunodeficiencies. Here, we study a patient with recurrent atypical mycobacterial infection and early-onset metastatic bladder carcinoma. Exome sequencing identified two homozygous missense germline mutations, P733L and P832S, in the JAK1 protein that mediates signalling from multiple cytokine receptors. Cells from this patient exhibit reduced JAK1 and STAT phosphorylation following cytokine stimulations, reduced induction of expression of interferon-regulated genes and dysregulated cytokine production; which are indicative of signalling defects in multiple immune response pathways including Interferon-γ production. Reconstitution experiments in the JAK1-deficient cells demonstrate that the impaired JAK1 function is mainly attributable to the effect of the P733L mutation. Further analyses of the mutant protein reveal a phosphorylation-independent role of JAK1 in signal transduction. These findings clarify JAK1 signalling mechanisms and demonstrate a critical function of JAK1 in protection against mycobacterial infection and possibly the immunological surveillance of cancer.Wellcome Trust (095198/Z/10/Z and 090233/Z/09/Z); Higher Education Funding Council for England; Great Ormond Street Hospital Children’s Charity; National Institute for Health Research (NIHR); Great Ormond Street Hospital Biomedical Research Centre; NIHR Cambridge Biomedical Research Centre; Alfonso Martin Escudero Foundatio