Transcriptomic profiling of TK2 deficient human skeletal muscle suggests a role for the p53 signalling pathway and identifies growth and differentiation factor-15 as a potential novel biomarker for mitochondrial myopathies

Background Mutations in the gene encoding thymidine kinase 2 (TK2) result in the myopathic form of mitochondrial DNA depletion syndrome which is a mitochondrial encephalomyopathy presenting in children. In order to unveil some of the mechanisms involved in this pathology and to identify potential biomarkers and therapeutic targets we have investigated the gene expression profile of human skeletal muscle deficient for TK2 using cDNA microarrays. Results We have analysed the whole transcriptome of skeletal muscle from patients with TK2 mutations and compared it to normal muscle and to muscle from patients with other mitochondrial myopathies. We have identified a set of over 700 genes which are differentially expressed in TK2 deficient muscle. Bioinformatics analysis reveals important changes in muscle metabolism, in particular, in glucose and glycogen utilisation, and activation of the starvation response which affects aminoacid and lipid metabolism. We have identified those transcriptional regulators which are likely to be responsible for the observed changes in gene expression. Conclusion Our data point towards the tumor suppressor p53 as the regulator at the centre of a network of genes which are responsible for a coordinated response to TK2 mutations which involves inflammation, activation of muscle cell death by apoptosis and induction of growth and differentiation factor 15 (GDF-15) in muscle and serum. We propose that GDF-15 may represent a potential novel biomarker for mitochondrial dysfunction although further studies are required

Evolución en el estudio de la relación entre factores psicológicos y fibromialgia

Este trabajo tiene como objetivo revisar la investigación psicosocial realizada durante la última década en la fibromialgia (F), uno de los síndromes de dolor crónico de origen reumático más comunes en la clínica cotidiana. En primer lugar, el interés fundamental de esta investigación ha sido la búsqueda de causalidad psicológica para el síndrome, sin que se hayan logrado resultados concluyentes al respecto. En segundo lugar, este trabajo pone de relieve la escasez de trabajos que estudian las cuestiones más actuales de la investigación psicosocial en el dolor crónico. En tercer lugar, durante la década revisada, no se ha estudiado el impacto psicosocial de la F, ni la contribución de los factores psicosociales a la experiencia de dolor del síndrome

The epidemiology of dermatomyositis in South Australia

The definitive version is available at www.blackwell-synergy.comAim: To review the epidemiology of dermatomyositis (DM) in South Australia (SA) and to compare it with other Australian states and New Zealand (NZ). Methods: Muscle biopsy and hospital separation data for DM in SA, other Australian states, and NZ were determined. The role of environmental factors was investigated. Results: From 1990 to 2005, there were 21 cases of biopsy-proven DM in SA (62% F, mean age 49.7 ± 18.4) and 99 cases of polymyositis (PM). Based on biopsy-proven figures, the average incidence of DM per year in SA was 1.4 ± 1.2, and 6.6 ± 2.6 for PM. Since 1991, there were 221 and 441 total separations from SA hospitals with principal diagnoses of DM and PM, respectively. The ratio DM/DM + PM is thought to correlate with solar irradiance, and within Australia, SA had the lowest ratio (0.39, 95% CI 0.22–0.56), with the highest ratio seen in WA (0.67, 95% CI 0.53–0.81). This ratio did not correlate with latitude, duration of sunshine, cloud cover, relative humidity or total rainfall. Within SA, no correlation with socioeconomic status was seen. Australian data were similar to NZ, where the ratios were 0.34 and 0.3 for North and South Islands, respectively. As separation data reflect total hospital visits, we also ascertained individual patient separations from SA hospitals (1997 to July 2005) and found a similar ratio of DM/DM + PM (0.38 ± 0.08). Conclusions: The proportion of inflammatory myositis which is DM varies nationwide, with a consistent ratio seen in SA (33–38%). Geoclimatic variables do not appear to influence DM/PM disease expression in Australia.Vidya Limaye, Peter Blumbergs, Grace Scott, Paul Hakendorf, Vladimir Stevanovic, John Highton, Peter Roberts-Thomso

The clinical features of dermatomyositis in a South Australian population

The definitive version is available at www.blackwell-synergy.comAim: To review the clinical features of dermatomyositis (DM) in a South Australian population. Methods: Retrospective review of medical records of patients with biopsy-proven DM in South Australia from 1990 to 2005. Results: There were 21 cases of biopsy-proven DM in SA (62% F, mean age 49.7 ± 18.4 years) and clinical details were available in 20 of these. Malignancy was identified in 9/20 patients; in five this followed the diagnosis of DM, with three malignancies seen within 3 months of disease onset. Three patients had a clearly defined immune insult prior to the diagnosis of DM; one patient had Mycoplasma pneumoniae infection 23 days prior to DM, two had pneumococcal and influenza vaccinations 5 and 14 days prior to the onset of DM, respectively. Two of three patients with anti-Jo-1 antibody experienced thromboembolism within 2 months of DM onset and three patients had interstitial lung disease (2 with anti-Jo-1 antibody). Creatine kinase (CK) was elevated in 15/20 cases and showed strong correlation with transaminases, and notably not with traditional inflammatory markers. Conclusions: This retrospective review of patients with biopsy-proven DM suggests a role for infection/vaccination in triggering disease onset. A particularly strong association with malignancy was observed and it is suggested that DM may predispose to thrombosis. Transaminases, in addition to CK may be used to monitor disease activity, and traditional inflammatory markers have little role in this.Vidya Limaye, Peter Blumbergs, Grace Scott, Peter Roberts-Thomso