T-cell specific upregulation of Sema4A as risk factor for autoimmunity in systemic lupus erythematosus and rheumatoid arthritis.

The aim of the present study was to evaluate the impact of SEMA4A genetic variants on expression of sema4A protein and its relation to autoimmunity development in Systemic Lupus Erythematosus and Rheumatoid Arthritis patients. A total of 541 SLE patients, 390 RA patients and 607 healthy individuals were genotyped. We also assessed SEMA4A mRNA expression from whole blood cells and the in vitro protein production from resting and activated T lymphocytes as well as mature dendritic cells from healthy individuals stratified according to their genotypes for SLE/RA associated SEMA4A variants. Our results showed that T/T genotype for rs3738581 SNP is associated with both RA and SLE development (p = .000053, OR = 2.35; p = .0019, OR = 2.07, respectively; statistical power = 100%) and also to an increased in vitro sema4A production in active T lymphocytes. Our findings are indicative of a T cell-specific upregulation of sema4A in the presence of T/T genotype, being a risk factor for SLE and RA.

Vitamin D receptor polymorphisms and expression profile in rheumatoid arthritis Brazilian patients.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and important joint commitment, being the most common systemic autoimmune disease worldwide. RA displays important genetic background with a variety of genes contributing to the immune balance breakdown. Recent studies have demonstrated that vitamin D, through its receptor (VDR), is able to regulate the immune balance and suppress the autoimmunity process, being a potential target in autoimmune diseases. In the present genetic association study, we assessed 5 Tag single nucleotide polymorphisms (SNPs) (rs11168268, rs2248098, rs1540339, rs4760648 and rs3890733), which cover most of the VDR gene, in three different Brazilian populations (from Northeast, Southeast and South Brazil). We also evaluated the VDR expression profile in whole blood and monocytes from RA patients. For genotyping study, 428 RA patients and 616 healthy controls were genotyped with fluorogenic allele specific probes on an ABI7500 platform. For gene expression study, VDR mRNA levels of 15 RA patients and 26 healthy individuals were assessed by RT-PCR. Our results showed that SNPs rs4760648 and rs3890733 are associated to RA susceptibility (p value = 0.0026, OR 1.31 and p value = 0.0091, OR 1.28 with statistical power = 0.999 and 0.993, respectively). Regarding RA clinical features, the studied SNPs did not show significant associations. The gene expression assays showed that VDR mRNA levels were down regulated in both whole blood (-3.3 fold) and monocytes (-3.2 fold) of RA patients when compared to healthy controls. Our results, the first reported for distinct Brazilian populations, support a role of the VDR gene in the susceptibility to RA.

Efeitos dos exercícios de alongamento muscular no tratamento da fibromialgia: uma revisão sistemática / Effects of muscle stretching exercises in the treatment of fibromyalgia: a systematic review

Objetivo: O presente trabalho tem como objetivo sistematizar evidências científicas sobre a utilização dos exercícios de alongamento muscular no tratamento da fibromialgia (FM). Metodologia: Foi realizado a partir de consulta retrospectiva, sem limite cronológico e linguístico, às bases de dados MedLine, LILACS, SciELO e PEDro, além da ferramenta de busca PubMed. A coleta foi realizada por dois revisores independentes, em outubro de 2012, sendo a estratégia de busca formulada por meio do cruzamento de descritores e termos relevantes para o tema nos idiomas inglês, português e espanhol. Foram incluídos ensaios clínicos randomizados (ECRs) compostos apenas por pacientes com diagnóstico clínico de FM e com exercícios de alongamento muscular como medida terapêutica em pelo menos um dos grupos de intervenção. Os estudos incluídos foram avaliados quanto à qualidade metodológica por meio da escala PEDro, e suas referências bibliográficas, analisadas, para se destacar fontes adicionais. A busca totalizou 6.794 artigos. Cinco artigos foram selecionados, sendo um deles excluído por apresentar baixa qualidade metodológica. A dor foi avaliada por unanimidade. O método e o tempo das intervenções variaram amplamente, houve falta de menção de parâmetros na utilização dos alongamentos e ausência de exames físicos específicos. Resultados: Houve melhora significativa em todos os estudos quanto à dor, além de aspectos relacionados a qualidade de vida e condição física. Conclusão: É evidente a importância do alongamento muscular no tratamento da FM, porém observa-se a necessidade de novos estudos para se estabelecer os reais benefícios da técnica, visto que a maioria dos trabalhos publicados apresenta baixa qualidade metodológica e ausência de padronização quanto ao uso desse recurso. .

Objective: this study has the objective to systematize scientific evidences about the use of muscle stretching exercises in the treatment of FM. Methodology: it was performed from retrospective research without chronological and linguistic limits, at databases of MEDLINE, LILACS, SciELO and PEDro, as well as at PubMed search tool. Data collection was performed by two independent reviewers in October 2012, with the search strategy formulated by crossing descriptors and relevant terms to the topic in English, Portuguese and Spanish languages. Randomized clinical trials, only with patients with a clinical diagnosis of fibromyalgia and muscle stretching exercises as a therapeutic measure at least in one of the intervention groups were included. Included studies were assessed for methodological quality using PEDro scale and their references analyzed to highlight additional sources. The search amounted to an average of 6,794 items. Only five articles were selected, one being excluded because of its low methodological quality. Pain was assessed unanimously. The method and timing of interventions varied widely, there was poor mention of the parameters used in the stretches and absence of specific physical examinations. Results: there was significant improvement in all studies regarding pain, besides as related to quality of life and physical condition. Conclusion: it is clear the importance of muscle stretching in the treatment of FM, however, there is a need for further studies to establish the real benefits of the technique, because the majority of published studies shows low methodological quality and there is a lack of standardization regarding the use of this resource. .

Effects of muscle stretching exercises in the treatment of fibromyalgia: a systematic review.

OBJECTIVE: This study has the objective to systematize scientific evidences about the use of muscle stretching exercises in the treatment of FM. METHODOLOGY: It was performed from retrospective research without chronological and linguistic limits, at databases of MEDLINE, LILACS, SciELO and PEDro, as well as at PubMed search tool. Data collection was performed by two independent reviewers in October 2012, with the search strategy formulated by crossing descriptors and relevant terms to the topic in English, Portuguese and Spanish languages. Randomized clinical trials, only with patients with a clinical diagnosis of fibromyalgia and muscle stretching exercises as a therapeutic measure at least in one of the intervention groups were included. Included studies were assessed for methodological quality using PEDro scale and their references analyzed to highlight additional sources. The search amounted to an average of 6,794 items. Only five articles were selected, one being excluded because of its low methodological quality. Pain was assessed unanimously. The method and timing of interventions varied widely, there was poor mention of the parameters used in the stretches and absence of specific physical examinations. RESULTS: There was significant improvement in all studies regarding pain, besides as related to quality of life and physical condition. CONCLUSION: It is clear the importance of muscle stretching in the treatment of FM, however, there is a need for further studies to establish the real benefits of the technique, because the majority of published studies shows low methodological quality and there is a lack of standardization regarding the use of this resource.