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ObjectivesTo study the effects of abatacept on disease activity and on muscle biopsy features of adult patients with dermatomyositis (DM) or polymyositis (PM).MethodsTwenty patients with DM (n=9) or PM (n=11) with refractory disease were enrolled in a randomised treatment delayed-start trial to receive either immediate active treatment with intravenous abatacept or a 3 month delayed-start. The primary endpoint was number of responders, defined by the International Myositis Assessment and Clinical Studies Group definition of improvement (DOI), after 6 months of treatment. Secondary endpoints included number of responders in the early treatment arm compared with the delayed treatment arm at 3 months. Repeated muscle biopsies were investigated for cellular markers and cytokines.Results8/19 patients included in the analyses achieved the DOI at 6 months. At 3 months of study, five (50%) patients were responders after active treatment but only one (11%) patient in the delayed treatment arm. Eight adverse events (AEs) were regarded as related to the drug, four mild and four moderate, and three serious AEs, none related to the drug. There was a significant increase in regulatory T cells (Tregs), whereas other markers were unchanged in repeated muscle biopsies.ConclusionsIn this pilot study, treatment of patients with DM and PM with abatacept resulted in lower disease activity in nearly half of the patients. In patients with repeat muscle biopsies, an increased frequency of Foxp3+ Tregs suggests a positive effect of treatment in muscle tissue.

ObjectiveThe first 3 months after symptom onset represent an important therapeutic window for rheumatoid arthritis (RA). This study investigates the extent and causes of delay in assessment of patients with RA in eight European countries.MethodData on the following levels of delay were collected from 10 centres (Berlin, Birmingham, Heraklion, Lund, Prague, Stockholm, Umeå, Vienna, Warsaw and Zurich): (1) from onset of RA symptoms to request to see healthcare professional (HCP); (2) from request to see HCP to assessment by that HCP; (3) from initial assessment by HCP to referral to rheumatologist; and (4) from referral to rheumatologist to assessment by that rheumatologist.ResultsData were collected from 482 patients with RA. The median delay across the 10 centres from symptom onset to assessment by the rheumatologist was 24 weeks, with the percentage of patients seen within 12 weeks of symptom onset ranging from 8% to 42%. There were important differences in the levels underlying the total delays at individual centres.ConclusionsThis research highlights the contribution of patients, professionals and health systems to treatment delay for patients with RA in Europe. Although some centres have strengths in minimising certain types of delay, interventions are required in all centres to ensure timely treatment for patients.

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 Classical (CM), non-classical (NCM) and intermediate populations of human monocytes are characterised by differential expression of CD14 and CD16. NCM and IM are potent antigen presenting cells and producers of pro-inflammatory cytokines. They are enriched in patients with established rheumatoid arthritis (RA) and their numbers correlate with disease activity and response to therapy with methotrexate (MTX) and glucocorticoids (GCS). CD11c plays a role in antigen presentation and production of pro-inflammatory cytokines. Increased expression of CD11c on mononuclear blood cells and a predictive role of higher CD11c mRNA expression for response to TNFα blocking treatment in RA were described. We evaluated the expression of CD11c on monocyte subpopulations in patients with early rheumatoid arthritis (ERA) and its changes after three months of treatment with GCS and non-biological disease modifying drugs. Materials and Methods 29 patients with ERA and 10 gender and age-matched healthy controls (HC) were included in this study. ERA patients had symptom duration for + CD16 - , NCM:CD14 dim CD16 ++ ) using multicolour flow cytometry. Based on isotype and FMO controls for CD14 and CD16; two intermediate (IM) populations were evaluated (CD14 + CD16 dim and CD14 + CD16 ++ ). CD11c expression was analysed by median fluorescence intensity. Results Expansion of both intermediate populations (IM-CD16 dim , p ++ , p = 0.02) and reduction of CM (p + or ++ and NCM: rs = -0.64, -0.55 or -0.50 and -0.40; p = 0.004, 0.08 or 0.02 and 0.09) at month three. No associations with disease activity or with MTX dosage were found. Conclusions The expansion of intermediate monocyte subpopulations in ERA patients and enhancement of CD11c expression with reduction after three months of treatment with GCS suggest their possible role in the pathogenesis of RA at early stages of the disease. Acknowledgement Institutional support MZCR0002372801

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 Specific or associated autoantibodes are present in a majority of patients with idiopathic inflammatory myopathies (IIM). The most frequent myositis associated autoautoantibodies are directed to Ro52-kd protein (present in 12–26%). Antibodies towards the immunodominant epitope (p200) of Ro52 are associated with neonatal heart block (CHB) in SLE and Sjogren9s syndrome (SjS) with the increasing evidence for their pathogenic role. Less is known about possible pathogenic involvement of anti-Ro52 in IIM. Presence of anti-Ro52 in patients with anti-Jo-1 autoantibody is associated with interstitial lung disease (ILD) and suggested decreased survival rate. Objective To investigate possible associations of reactivity to Ro52 epitopes with disease manifestations, autoantibody profile and HLA-DRB1 alleles in myositis. In order to confirm the hypothesis of ongoing epitope spreading with time, the association of disease duration with polyreactivity was evaluated. Methods Serum samples from 468 myositis patients were collected in three countries: Czech (n=133); Hungary (n=202), Sweden (n=133). Antibody specificity against recombinant full length (FL) Ro52 antigen, its four deletion fragments (Ro52-3, -4, -5 and -6) and 7 overlapping synthetic peptides (p136–200) covering the major immunodominant region (Ro52-3) was measured by ELISA. Myositis specific and associated autoantibodies (Jo-1, PL-7, PL-12, EJ, OJ, SRP, PM-Scl, Ku, Mi-2β, U1-RNP) were detected by line-blot immunoassay. 417 patients were genotyped for HLA-DRB1. Results One hundred and eighty-four patients with dermatomyositis (DM), 250 polymyositis (PM), 11 inclusion body myositis, 20 juvenile DM/PM and three with mixed connective tissue disease were included in the analysis. Overlap with other systemic disease (OM) was present in 67 (14%) and ILD in 132 (29%) of patients. Median disease duration was 4.7 (0–41.5) years. Reactivity to Ro52-FL was present in 97 (21%) samples. Of these, 87 (90%) patients showed specificity to Ro52-3. Within these anti-p176 dominated (66; 76%) compared to anti-p200 in 44 (51%) patients. Anti-Ro52FL positivity was associated with presence of ILD (OR 3.8; p Conclusion Our results confirm the association between anti-Ro52 autoantibody positivity with lung involvement, anti-Jo-1 autoantibodies and HLA-DRB1*03 allele in myositis. The predominance of reactivity to epitope p176 in myositis patients is different from that which has been reported in patients with SLE and SjS, but the clinical significance is not clear. There was no evidence of epitope spreading in anti-Ro52 response. Acknowledgement Supported by European Union 6.FP integrated project AutoCure LSHB CT-2006-018661; by MSM 0021620812 from Ministry of Education, Youth and Sports in the Czech Republic and by Grant NT 12438 of IGA Ministry of Health in the Czech Republic.