Abstract: Objective: To study the B-cell content, organization, and existence of distinct B-cell subpopulations in relation to the expression of type 1 interferon signature related genes in dermatomyositis (DM). Methods: Evaluation of skeletal muscle biopsies from patients with adult DM (aDM) and juvenile DM (jDM) by histology, immunohistochemistry, electron microscopy, and quantitative reverse-transcription PCR. Results: We defined 3 aDM subgroups--classic (containing occasional B cells without clusters), B-cell-rich, and follicle-like aDM--further elucidating IM B-lymphocyte maturation and immunity. The quantity of B cells and formation of ectopic lymphoid structures in a subset of patients with aDM were associated with a specific profile of cytokines and chemokines involved in lymphoid neogenesis. Levels of type 1 interferon signature related gene expression paralleled B-cell content and architectural organization and link B-cell immunity to the interferon type I signature. Conclusion: These data corroborate the important role of B cells in DM, highlighting the direct link between humoral mechanisms as key players in B-cell immunity and the role of type I interferon-related immunity

Idiopathic inflammatory myopathies (IIM) are severe inflammatory muscle disorders with life threatning complications. Treatments are partially efficacious and have many side effects. Thus new therapeutics approaches have to be developed. Because IIM involves auto-immune mechanisms and CD4+CD25+FoxP3+ regulatory T lymphocytes (Treg) play a major role in the regulation of immune responses, we examined the role of Treg in IIM. First, we developed a reproducible and transferable model of auto-immune myopathy. This experimental autoimmune myositis (EAM) was aggravated by Treg depletion and improved by polyclonal Treg injection. Furthermore rapamycin decreases the severity of the myositis in EAM mice by increasing the percentage Treg in the draining lymph nodes. We also analysed Treg in patients with inclusion boby myositis (IBM), an IIM without validated treatment. In IBM patients we observed an activation of the immune system engaged in a Th1 response, with a decreased percentage of Treg in the periphery. Treg are present within muscular infiltrates where they seem unable to control inflammation. Finally, in attempt to define reliable outcomes in IBM patients for clinical trials, we assessed muscle strength during a nine months period. We found that knee extension strength seems to be the most relevant marker of disease progression in IBM when measured with suitable dynamometry.Together these data suggest that rapamycin could be tested as treatment for IBM patient using knee extension strength as outcome measure

L'utilisation de "tert"-leucinates de dirhodium(II) tels que le Rh2{(S)-NTTL}4 et le Rh2{(S)-PTTL}4 a permis d'obtenir les inductions asymétriques optimales.