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Idiopathic inflammatory myopathies (IIM) belong to a group of autoimmune disorders, primarily characterized by chronic inflammation of human skeletal muscle tissue. The etiology of these diseases is unknown, however, genetic predisposition plays a significant role in disease onset. Beside the known genetic risk located in the MHC complex, the epigenetic modifications including changes in miRNAs expression profiles have been recently implicated recently in many autoimmune diseases. Micro RNA molecules are involved in many physiological processes, including the regulation of the immune response.In our study we have focused on the miR-23b, as it represents a novel promising autoimmunity regulator molecule. Downregulation of miR-23b was recently described in patients with rheumatoid arthritis and systemic lupus erythematosus. We have measured the expression miR-23b peripheral blood mononuclear cells of patients with dermatomyositis and polymyositis. No meaningful difference was found in comparison with healthy controls.

Background and objectives Genes within the major histocompatibility complex (MHC) region has a strong genetic relevance in autoimmunity development. The involvement of the class I and class II genes, as well as class III (non-Class I/II MHC) genes has been proposed. For the myositis development, the HLA-DRB1*03 is a known risk factor in Caucasian population. However, there are another genes appearing to be significant players in the ethiology of myositis located near the HLA-DRB1 locus. In the present study the authors have focused on one of these risk factors – the regulation of MHC-linked inducible HSP70 genes expression and their relation to the known immunogenetic risk factor located within the MHC (HLA-DRB1*03). Materials and methods The authors have investigated the gene specific HSP70 expression in 20 patients with dermatopolymyositis and 15 healthy people matching in age as control samples. Expression levels of the two inducible HSP70 genes ( HSPA1A , HSPA1B ) were analysed both in patients and controls. Both of the groups were additionally genotyped for HLA-DRB1 locus. Myositis-specific and associated autoantibodies were also identified in patients. Results The expression of both, the HSPA1A and HSPA1B genes was significantly upregulated (p HSPA1A was found to be associated with the presence of the HLA-DRB1*03 risk allele in patients. However, this was not observed for the HSPA1B gene. In contrast, the authors found a positive correlation between the expression regulation of the HSPA1B gene and the presence of disease specific autoantibodies in myositis patients. Additionally, positive correlation between the presence of disease specific autoantibodies and the HLA-DRB1*03 risk allele was found. None of these observations were found in healthy controls. Conclusions The results suggest that the two MHC-linked inducible genes are differentially expressed in dependence on the autoantibody or HLA risk allele presence. The differential gene expression regulation shows that the HSPA1B is an – on HLA-DRB1 – independent molecular marker for myositis development.

Background and Objectives MicroRNAs can regulate the gene expression and cellular functions such as cell cycle, differentiation, or apoptosis. Emerging evidence has demonstrated that miRNAs play a vital role also in the regulation of immunological functions, including the development of autoimmunity. Like in most of other autoimmune diseases, the etiopathogenesis of Idiopathic inflammatory myopathy (IIM) is also believed to be triggered by environmental factors in combination with susceptible genetic background. Beside a genetic risk located within the MHC complex, the role of epigenetic regulations including changes in miRNAs expression profiles in autoimmunity development have recently also been implicated. The aim of this study was to look for specific miRNA expression patterns in the serum, peripheral blood mononuclear cells (PBMCs) and muscle biopsies of patients suffering from idiopathic inflammatory myopathy. Materials and Methods RNA was isolated from serum, PBMCs and muscle biopsy samples of patients suffering from IIM using modified Trizol-chloroform method. The expression profile of miRNAs was determined by 60K high density microarray from Agilent Company. Results In total, 87 miRNAs were found to be differentially expressed at a significant level (p Conclusions This is the first study providing information about complete expression profile of miRNA molecules found in the serum, PBMCs and muscle biopsy samples of patients with IIM. We have found that a number of miRNAs were differentially expressed in diverse tissue samples indicating tissue specific expression of miRNAs. The “missregulated” miRNAs might potentially act as biomarkers of initiated systemic inflammatory response, or functional molecules related to muscle tissue injury, or molecules involved in regulation of immune response. Acknowledgement This study was supported by the Internal Grant Agency of the Ministry of Health in the Czech Republic [MZCR NT 12452-4], Institutional support of MHCR VZ (00023728) and The Charles University Grant Agency (No.621812).

Background Idiopathic inflammatory myopathies (IIMs) are chronic autoimmune disorders characterized by skeletal muscle weakness, inflammatory immune cells in muscle tissues and frequent presence of serum autoantibodies. Besides a genetic risk located within the MHC complex, also epigenetic regulations including changes in miRNAs expression profiles have been implicated recently in many autoimmune diseases. Extracellular miRNAs circulate in the bloodstream and such miRNAs are remarkably stable. It is hypothesized that circulating miRNA may be delivered to recipient cells and regulate translation of target genes. Objectives The aim of this study was to analyze the differences in expression profiles of circulating extracellular miRNAs between patients and controls with possible selection of relevant candidate miRNA molecules involved in disease progression. Methods Expression profile of 1,347 miRNA molecules was analyzed in 47 myositis patients and 16 healthy controls. Circulating miRNAs were prepared from serum using the Trizol® reagent. The expression of miRNAs was measured using the 44K high density microarray from Agilent Company. Results The miRNA expression profiles clearly separate between healthy controls and patients with myositis. In total, 87 miRNA molecules were found to be differentially expressed in myositis patients. Analysis of the associated biological pathways regulated by the detected miRNAs revealed that 44 (50%) differentially expressed miRNAs are predicted to regulate immune response, 38 (43%) miRNAs are related to muscle activity and 40 (46%) miRNAs were predicted to be involved in cell death. Conclusions A number of miRNAs differentially expressed in patients with IIMs were identified. These molecules are potentially involved in the etiopathogenesis of the disease since all are related to important immune mechanisms or muscle function. Acknowledgements This study was supported by the Internal Grant Agency of the Ministry of Health in the Czech Republic [MZCR NT 12452-4], Institutional support of MHCR VZ (00023728) and The Charles University Grant agency (No.621812). Disclosure of Interest None Declared

Background and Objectives The idiopathic inflammatory myopathies (IIM) are systemic connective tissue diseases in which autoimmune pathology is responsible for promotion of chronic muscle inflammation and weakness. As in many other autoimmune diseases, the development of IIM is also associated with genes of HLA complex. The aim of this study was to determine the basic relation between alleles of HLA genes and IIM. Materials and Methods We have performed low to high resolution genotyping to characterise the allelic profiles of HLA-DRB1, -DQB1 and -DQA1 loci in a large group of single centre cohort of patients suffering from IIM (n = 269). The genomic DNA was prepared by standard DNA extraction methods and the HLA typing was done using the commercial LABType® SSO kit (One Lambda, USA). Statistical evaluation of results was done with chi-2 test and Fisher exact test. Autoantibody profiles were analysed with radioactive immunoprecipitation. Results The frequencies of HLA-DRB1*03:01 and -DRB1*16:01 alleles were increased in IIM patients and the difference reached statistical significance when compared to healthy controls (P Presence of HLA-DRB1*03:01 allele was associated with anti-Jo-1, anti-Ro52, or anti-Pm-Scl positivity in all IIM patients (P The DRB1*16:01 allele was associated with negativity of all studied autoantibodies, particularly in subgroup of DM patients (P Conclusions This study identifies different genetic background between patients with dermatomyositis and polymyositis in a homogenous population of patients from a single centre. Acknowledgement This work is supported by Internal Grant Agency of Ministry of Health of the Czech Republic NT/12438–4 and NT/13699.