Biomarkers in Inflammatory Myopathies – An Expanded Definition

Biomarkers as parameters of pathophysiological conditions can be of outmost relevance for inflammatory myopathies. They are particularly warranted to inform about diagnostic, prognostic, and therapeutic questions. As biomarkers become more and more relevant in daily routine, this review focusses on relevant aspects particularly addressing myopathological features. However, the level of evidence to use them in daily routine at presence is low, still since none of them has been validated in large cohorts of patients and rarely in independent biopsy series. Hence, they should be read as mere expert opinions. The evaluation of biomarkers as well as key biological parameters is an ongoing process, and we start learning about relevance of them, as we must recognize that pathophysiology of myositis is biologically incompletely understood. As such this approach should be considered an essay toward expansion of the definition “biomarker” to myositis, an emerging field of interest in biomedical research

Corpus oraux, Guide des bonnes pratiques 2006. Version allemande

International audienceViele Grundlagen- oder angewandte Forschungen beruhen zur Zeit auf der Auswertung von „Korpora der gesprochenen Sprache“ (geordneten Sammelwerken der Aufnahmen von mündlichen und multimodalen sprachlichen Produktionen). Dieses Handbuch der guten Praktiken entsteht aus der Erkenntnis von Sprachwissenschaftlern, die darauf bedacht sind, den Fortbestand der Quellen und einen verschiedenartigen Zugang zu den mündlichen von ihnen produzierten Produktionen zu sichern ; es schneidet zuerst die „Korpora der gesprochenen Sprache“ an, die von Sprachwissenschaftlern und für sie geschaffen und verwendet wurden. Die durch die Erschaffung und die dokumentarische Auswertung dieser Korpora hervorgerufenen Fragen trifft man aber in vielen Fächern : die Völkerkunde, die Anthropologie, die Soziologie, die Psychologie, die Demographie, die mündlich überlieferte Geschichte gebrauchen vor allem die verbale Befragung, die Aussage, das Interview, die Lebensgeschichte. Dieses Handbuch beruft sich auf das Verfahren der Sprachwissenschaftler, es stimmt aber mit den Beschäftigungen anderer Forscher überein, die Korpora der gesprochenen Sprache (z. B. in Sprachsynthese und -entzifferung) gebrauchen, auch wenn ihre spezifischen Bedürfnisse im vorliegenden Dokument nicht systematisch angeschnitten werden

Spoken Corpora Good Practice Guide 2006

International audienceThere is currently a vast amount of fundamental or applied research, which is based on the exploitation of oral corpora (organized recorded collections of oral and multimodal language productions). Created as a result of linguists becoming aware of the importance to ensure the durability of sources and a diversified access to the oral documents they produce, this Guide to good practice mainly deals with “oral corpora”, created for and used by linguists. But the questions raised by the creation and documentary exploitation of these corpora can be found in numerous disciplines: ethnology, anthropology, sociology, psychology, demography, oral history notably use oral surveys, testimonies, interviews, life stories. Based on a linguistic approach, this Guide also touches on the preoccupations of other researchers who use oral corpora (for example in the field of speech synthesis and recognition), even if their specific needs aren’t consistently dealt with in the present document

Sequestosome‐1 (p62) expression reveals chaperone‐assisted selective autophagy in immune‐mediated necrotizing myopathies

Diffuse myofiber necrosis in the context of inflammatory myopathy is the hallmark of immune-mediated necrotizing myopathy (IMNM). We have previously shown that skeletal muscle fibers of IMNM patients may display nonrimmed vacuoles and sarcoplasmic irregularities. The dysfunctional chaperone activity has been linked to the defective assembly of skeletal muscle proteins and their degradation via lysosomes, autophagy and the proteasomal machinery. This study was undertaken to highlight a chaperone-assisted selective autophagy (CASA) pathway, functionally involved in protein homeostasis, cell stress and the immune response in skeletal muscle of IMNM patients. Skeletal muscle biopsies from 54 IMNM patients were analyzed by immunostaining, as well as by qPCR. Eight biopsies of sIBM patients served as pathological controls, and eight biopsies of nondisease control subjects were included. Alteration of autophagy was detectable in all IMNM biopsy samples highlighted via a diffuse sarcoplasmic staining pattern by p62 and LC3 independent of vacuoles. This pattern was at variance with the coarse focal staining pattern mostly confined to rimmed vacuoles in sIBM. Colocalization of p62 with the chaperone proteins HSP70 and alpha B-crystalline points to the specific targeting of misfolded proteins to the CASA machinery. Bcl2-associated athanogene 3 (BAG3) positivity of these fibers emphasizes the selectivity of autophagy processes and these fibers also express MHC class I sarcolemma. Expression of genes involved in autophagy and endoplasmic reticulum (ER) stress pathways studied here is significantly upregulated in IMNM. We highlight that vacuoles without sarcolemmal features may arise in IMNM muscle biopsies, and they must not be confounded with sIBM-specific vacuoles. Further, we show the activation of selective autophagy and emphasize the role of chaperones in this context. CASA occurs in IMNM muscle, and specific molecular pathways of autophagy differ from the ones in sIBM, with p62 as a unique identifier of this process

Online Training on Skin Cancer Diagnosis in Rheumatologists: Results from a Nationwide Randomized Web-Based Survey

International audiencePatients with inflammatory rheumatisms, such as rheumatoid arthritis, are more prone to develop skin cancers than the general population, with an additional increased incidence when receiving TNF blockers. There is therefore a need that physicians treating patients affected with inflammatory rheumatisms with TNF blockers recognize malignant skin lesions, requiring an urgent referral to the dermatologist and a potential withdrawal or modification of the immunomodulatory treatment. We aimed to demonstrate that an online training dedicated to skin tumors increase the abilities of rheumatologists to discriminate skin cancers from benign skin tumors. A nationwide randomized web-based survey involving 141 French rheumatologists was conducted. The baseline evaluation included short cases with skin lesion pictures and multiple choice questions assessing basic knowledge on skin cancers. For each case, rheumatologists had to indicate the nature of skin lesion (benign; premalignant/ malignant), their level of confidence in this diagnosis (10-points Likert scale), and the precise dermatological diagnosis among 5 propositions. Different scores were established. After randomization, only one group had access to the online formation consisting in 4 elearning modules on skin tumors, of 15 minutes each (online training group). After reevaluation, the trained and the non-trained group (control group) were compared. The primary end-point was the number of adequate diagnoses of the nature of the skin lesions. The mean number of adequate diagnosis for the benign versus premalignant/malignant nature of the lesions was higher in the online training group (13.4 vs. 11.2 points; p value <0.0001). While the other knowledge scores were also significantly higher, no statistical difference was observed on the level of self-confidence between the 2 groups. In conclusion, the online formation was effective to improve the rheumatologists' ability to diagnose skin cancer

The INDC counter, aggregation of national contributrions and 2°C trajectories

Rapport du groupe interdisciplinaire sur les contributions nationalesConsidering that limiting global warming to below 2°C implies a CO2 budget not to be exceeded and near-zero emissions by 21OO (IPCC), we can assess global 2030 greenhouse gas emissions implied by INDCs in comparison to long-term trajectories. Ahead of the COP21, we estimate that submitted INDCs would bring global greenhouse gas emissions in the range of 55 to 64 GtC02eq in 2030.Under this assumption,global emissions in 2030 are thus higher than the level of 51GtC0 2eq for the year 2012. However, this is not in contradiction with a peaking of global emissions that can only be expected after 2020, given in particular the projected dynamics of emissions in China and other developing countries.The published INDCs represent a significant step towards trajectories compatible with the 2°C goal,but remain insufficient to join trajectories presenting a reasonable probability of success.ln order to increase the chance of meeting the 2°C objective, the ambition of the short-term contributions needs to be strengthened in future negotiations.ln order to sustain a high pace in emissions reductions after 2030,structural measures are also needed, which, in order to have a rapi impact, should be prepared as early as possible. Continued efforts are needed to accelerate the development of low carbon solutions on the one hand,and demonstrate the feasibility of negative emissions on the other hand

In Antisynthetase Syndrome, ACPA Are Associated With Severe and Erosive Arthritis: An Overlapping Rheumatoid Arthritis and Antisynthetase Syndrome

International audienceAbstract: Anticitrullinated peptide/protein antibodies (ACPA), which are highly specific for rheumatoid arthritis (RA), may be found in some patients with other systemic autoimmune diseases. The clinical significance of ACPA in patients with antisynthetase syndrome (ASS), a systemic disease characterized by the association of myositis, interstitial lung disease, polyarthralgia, and/or polyarthritis, has not yet been evaluated with regard to phenotype, prognosis, and response to treatment. ACPA-positive ASS patients were first identified among a French multicenter registry of patients with ASS. Additionally, all French rheumatology and internal medicine practitioners registered on the Club Rhumatismes et Inflammation web site were asked to report their observations of ASS patients with ACPA. The 17 collected patients were retrospectively studied using a standardized questionnaire and compared with 34 unselected ACPA-negative ASS patients in a case–control study. All ACPA-positive ASS patients suffered from arthritis versus 41% in the control group (P 7-year mean follow-up, extra-articular outcomes and survival were not different. ACPA-positive ASS patients showed an overlapping RA–ASS syndrome, were at high risk of refractory erosive arthritis, and might experience ASS flare when treated with antitumor necrosis factor drugs. In contrast, other biologics such as anti-CD20 mAb were effective in this context, without worsening systemic involvements

The EuroMyositis registry: an international collaborative tool to facilitate myositis research

Aims: The EuroMyositis Registry facilitates collaboration across the idiopathic inflammatory myopathy (IIM) research community. This inaugural report examines pooled Registry data. Methods: Cross-sectional analysis of IIM cases from 11 countries was performed. Associations between clinical subtypes, extramuscular involvement, environmental exposures and medications were investigated. Results: Of 3067 IIM cases, 69% were female. The most common IIM subtype was dermatomyositis (DM) (31%). Smoking was more frequent in connective tissue disease overlap cases (45%, OR 1.44, 95% CI 1.09 to 1.90, p=0.012). Smoking was associated with interstitial lung disease (ILD) (OR 1.32, 95% CI 1.06 to 1.65, p=0.013), dysphagia (OR 1.43, 95% CI 1.16 to 1.77, p=0.001), malignancy ever (OR 1.78, 95% CI 1.36 to 2.33, p<0.001) and cardiac involvement (OR 2.40, 95% CI 1.60 to 3.60, p<0.001). Dysphagia occurred in 39% and cardiac involvement in 9%; either occurrence was associated with higher Health Assessment Questionnaire (HAQ) scores (adjusted OR 1.79, 95% CI 1.43 to 2.23, p<0.001). HAQ scores were also higher in inclusion body myositis cases (adjusted OR 3.85, 95% CI 2.52 to 5.90, p<0.001). Malignancy (ever) occurred in 13%, most commonly in DM (20%, OR 2.06, 95% CI 1.65 to 2.57, p<0.001). ILD occurred in 30%, most frequently in antisynthetase syndrome (71%, OR 10.7, 95% CI 8.6 to 13.4, p<0.001). Rash characteristics differed between adult-onset and juvenile-onset DM cases ('V' sign: 56% DM vs 16% juvenile-DM, OR 0.16, 95% CI 0.07 to 0.36, p<0.001). Glucocorticoids were used in 98% of cases, methotrexate in 71% and azathioprine in 51%. Conclusion: This large multicentre cohort demonstrates the importance of extramuscular involvement in patients with IIM, its association with smoking and its influence on disease severity. Our findings emphasise that IIM is a multisystem inflammatory disease and will help inform prognosis and clinical management of patients

Genome-wide imputation identifies novel associations and localises signals in idiopathic inflammatory myopathies.

OBJECTIVES The idiopathic inflammatory myopathies (IIM) are heterogeneous diseases, thought to be initiated by immune activation in genetically predisposed individuals. In this study we imputed variants from the Immunochip array using a large reference panel to fine-map associations and identify novel associations in IIM. METHODS We analysed 2,565 Caucasian IIM samples collected through the Myositis Genetics Consortium (MYOGEN) and 10,260 ethnically-matched controls. We imputed 1,648,116 variants from the Immunochip array using the Haplotype Reference Consortium panel and conducted association analysis on IIM, and clinical and serological subgroups. RESULTS The human leukocyte antigen (HLA) locus was consistently the most significantly associated region. Four non-HLA regions reached genome-wide significance, three in the whole IIM cohort (SDK2 and LINC00924 - both novel, and STAT4), with evidence of independent variants in STAT4, and NAB1 in the polymyositis (PM) subgroup. We also found suggestive evidence of association with loci previously associated with other autoimmune rheumatic diseases (TEC and LTBR). We identified more significant associations than those previously reported in IIM, for STAT4 and DGKQ in the total cohort, for NAB1 and FAM167A-BLK loci in PM, and CCR5 in inclusion body myositis. We found enrichment of variants among DNase I hypersensitivity sites and histone marks associated with active transcription within blood cells. CONCLUSIONS We report novel and strong associations in IIM and PM, and localise signals to single genes and immune cell types. This article is protected by copyright. All rights reserved