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Background:Since first described, our understanding of polymyositis (PM) has evolved substantially. Patients previously diagnosed with PM may now be better described as having an alternative diagnosis, including immune-mediated necrotizing myopathy (IMNM), connective tissue disease overlap myositis (CTD-OM), anti-synthetase syndrome (ASS) or inclusion body myositis (IBM).Objectives:To apply the current understanding of IIM subtypes to retrospectively review the diagnosis of patients classified as PM at our centre.Methods:We reviewed a cohort of 255 patients from a UK tertiary myositis clinic, with 37 patients classified as PM according to the EULAR/ACR IIM criteria and expert opinion (1). Consensus decisions made as to whether reclassification as an alternative IIM subtype would be appropriate in each case.Results:Thirty-seven patients with PM diagnosis according to EULAR/ACR IIM criteria and expert opinion were included in the analysis. Twenty-six patients (26/37, 68.4%) were female. The mean age at diagnosis was 57 years (SD 16.25) and mean follow up was 5.2 years (SD 4.8).After consensus discussions, ten patients (27%) retained classification as PM, representing 3.9% (10/255) of the original cohort of 255 patients. The remaining 27 were reclassified as follows: 7 CTD-OM (18.9%), 6 IMNM (16.2%), 6 unspecified myopathy (16.2%), 2 DM (5.4%), 1 IBM (2.7%), and 1 non-inflammatory myopathy (2.7%, myofibrillar myopathy). Four patients (10%) had insufficient data available to allow for a defined diagnosis.Of the 10 patients retaining classification as PM, 7 (70%) were female and mean age at diagnosis was 58.9 years. Clinical characteristics are represented in table 1. Mean CK at diagnosis was 2321 IU/L. Four patients (40%) were ANA positive, 8 patients (80%) were tested for the complete myositis antibody panel and 8 (80%) were specifically tested for the presence of HMGCR antibodies (figure 1). EMG revealed a myopathic pattern in 6/7 patients tested, while MRI demonstrated muscle oedema compatible with myositis in 3/5 of the patients that were tested. A complete muscle biopsy report was available in 8/10 PM-classified patients (80%), diffuse HLA-1 upregulation was present in 5 patients (50%), endomysial inflammatory infiltrates in 5 (50%) and perimysial infiltrates (in conjunction with endomysial infiltrates) in 3 (30%). No other specific features were found.Table 1.Clinical features.PM (n=10)CTD-OM (n=7)IMNM (n=6)All (n=37)Pyrexia0001 (2.7 %)Weight loss2 (20%)2 (28.6%)2 (33.3%)6 (16.2 %)Cutaneous rash01 (14.3%)02 (5.4 %)Mechanic’s hands1 (10%)2 (28.6%)04 (10.8 %)Sclerodactyly01 (14.3%)01 (2.7 %)Periungual erythema01 (14.3%)02 (5.3 %)Raynaud’s05 (71.4%)08 (21.6 %)Arthralgia05 (71.4%)08 (21.6 %)Arthritis02 (28.6%)05 (13.5 %)Muscle weakness10 (100%)7 (100%)6 (100%)36 (97.2%)Myalgia3 (30%)5 (71.4%)3 (50%)20 (54 %)Dysphagia3 (30%)5 (71.4%)1 (16.7%)13 (35.1 %)Interstitial lung disease (ILD)03 (42.9%)04 (10.5 %)Malignancy1 (9.1%)02 (33.3%)3 (8.1%)Conclusion:This study confirms that PM can now be considered a rare IIM subtype. A thorough examination, complete myositis antibody panel including HMGCR testing and careful interpretation of the biopsy results is recommended to accurately classify these patients.References:[1]Parker MJS, Oldroyd A, Roberts ME, Lilleker JB, Betteridge ZE, McHugh NJ, et al. The performance of the European League Against Rheumatism/American College of Rheumatology idiopathic inflammatory myopathies classification criteria in an expert-defined 10 year incident cohort. Rheumatol (United Kingdom). 2019 Mar 1;58(3):468–75Disclosure of Interests:None declared

Background:Overlap syndromes are autoimmune disorders in which classification criteria of at least two connective tissue diseases (CTDs) are fulfilled. The Division of Clinical Immunology in Debrecen, Hungary oversees patients with idiopathic inflammatory myopathies (IIMs) since the 1980’s.Objectives:In a work called The Myositis Antibody Research Project, which is coordinated together with the Bath Institute for Rheumatic Diseases (UK), authors investigated 330 patients with myositis, all treated in this Hungarian center.Methods:The aim of this retrospective study was to investigate the frequency, clinical and serological parameters and therapeutic options in myositis – rheumatoid arthritis overlap cases in this group of 330 patients.Results:The frequency of overlap cases, as seen in literature, was 13.64%. The importance of myositis-associated antibodies (MAAs) can be seen on this results: 44.44% of overlap patients, while only 7.02% of not overlap patients were MAA positive. Out of our 45 overlap patients twenty-seven myositis - RA overlap patients could be identified. Among these 27 patients the women:men ratio was 12.5:1, PM:DM ratio was 2.375:1. Muscle weakness and sceletal involvement was present in every patient, myalgia in 77.78% and Raynaud’s phenomenon in 48.15% of the patients; general symptoms during disease relapse (fatigue, weight loss, fever) were present in 59.26%, 18.52% and 14.82%, respectively. Ten cases had seropositive rheumatoid arthritis, with high titer of rheumatoid factor. Authors underline the importance of lung involvement as internal organ manifestation: 8 patients had anti-synthetase antibodies (six anti-Jo-1, one anti-PL-7 and one anti-PL-12). In anti-PL-7 and anti-PL-12 positive patients interstitial lung disease (ILD) appeared some years before myositis and early agressive management of ILD resulted in fast remission of muscle weakness. Anti-Mi-2 and anti-SRP could be detected in two patients. Most frequent used disease modifying antirheumatic drugs were cyclophosphamide, methotrexate and cyclosporine, 19 patients received DMARD combination therapy. Biological therapy was used in 3 patients, intravenous or subcutaneous immuneglobulin in 4 patients and one patient with RA – myositis – antiphospholipid syndrome died because of asipartion pneumonia.Conclusion:Authors conclude that it is really challenging to treat these overlap cases: they form a very heterogenous group of patients and management has to be personalized.Disclosure of Interests:None declared

Objectives: Autoantibodies to a novel autoantigen small ubiquitin-like modifier activating enzyme (SAE) associated with dermatomyositis (DM) have previously been identified. The aim of this study was to establish the frequency of anti-SAE autoantibodies in a UK myositis cohort and investigate clinicoimmunogenetic associations. Methods: Clinical data and sera were studied from 266 patients recruited to the Adult Onset Myositis Immunogenetic Collaboration. Myositis sera, control sera including 250 patients with other connective tissue diseases and 50 healthy participants were screened using radio-immunoprecipitation. Immunodepletion was performed on all sera immunoprecipitating 40 and 90 kDa bands to confirm the presence of anti-SAE. DNA from 202 patients with myositis was genotyped for human leucocyte antigen (HLA)-DRB1 and DQB1; DQA1 data were inferred. Results: Out of 266 patients with myositis, 11 (4%) were positive for anti-SAE, which was found exclusively in DM with a frequency of 8%. Patients with anti-SAE had a high frequency of cutaneous lesions including heliotrope (82%) and Gottron rash (82%). Of the 11, 9 (82%) had systemic features and 7 of 9 (78%) developed dysphagia. Of those nine, seven (78%) presented with skin disease before myositis onset. All patients with anti-SAE possessed at least one copy of HLA-DQB1*03. HLA-DRB1*04-DQA1*03-DQB1*03 was a significant risk factor in anti-SAE positive versus patients who were anti-SAE negative (haplotype frequency 18% vs 6%, p Conclusions: Anti-SAE is a myositis-specific autoantibody that identifies a subset of patients with adult DM. The majority of patients with anti-SAE presented with cutaneous disease and progressed to myositis with systemic features including dysphagia. This novel autoantibody has a strong association with the HLA-DRB1*04-DQA1*03-DQB1*03 haplotype.

Background B-cell activating factor of the TNF family (BAFF)is important for B cell maturationand plays a role in (auto)antibodies production. Elevated serum levels in relation to autoantibodies were documented in patients with IIMs. Promoter region of BAFF gene contains several known sites with single nucleotide polymorphism (SNPs). An association between rs9514828 (-871 C/T) SNP and susceptibility to idiopathic thrombocytopenic purpura was shown and possible relations to systemic lupus erythematosus, rheumatoid arthritis or Sjogren’s syndrome were suggested. Objectives To describe four BAFF SNPs located in the BAFF gene promoter in patients with IIMs and analyze relation of particular SNPs to serum BAFF (s-BAFF) levels in autoantibody positive patients. Methods Patients with polymyositis (n=146), dermatomyositis (DM, n=150), juvenile DM (n=11), inclusion body myositis (n=4) and 103 healthy individuals were included. Four SNPs located upstream in the BAFF gene (rs9514827 (-2841 T/C); rs3759467 (-2704 T/C); rs1041569 (-2701 T/A); rs9514828 (-871 C/T)) were analyzed by direct DNA sequencing. Levels of s-BAFF were measured using ELISA. Autoantibodies were detected with immunoprecipitation and Line blot assay. The chi square test for analysis of alleles and genotypes associations and SNPStats software for haplotype frequency studies wereused. Results Significantly higher frequency of -2701T allele was present in patients (18%) compared to healthy controls (12%) (p=0.029; OR 1.68 (CI 95%=1.05-2.7)). Additionally, increased -2841T allele (p=0.09), -2841TT, CT genotype (p=0.07) and -2701TT, AT genotype (p=0.08) frequencies were observed in patients. SNPs were in strong linkage disequilibrium and formed four common haplotypes (TTAC, CTAT, TCAC, TTTT), with significantly different frequency (> 9%) distributions between patients and controls (global P=0.038). Higher frequency of TTTT haplotype was present in patients (16%) compared to controls (9%; OR 1.99 (95% CI 1.15-3.47; P=0.015)) relative to the most frequent haplotype TTAC. Significantly higher s-BAFF levels were detected in patients compared to healthy controls (P Conclusions -2701T allele and TTTT haplotype in the four SNPs located upstream of the BAFF gene were associated with the presence of myositis. Patients with anti-Jo-1 antibodies have higher BAFF levels if they are carriers of -2704T allele. These findings point to differential genetic regulation of BAFF production in patients with IIMs, but need to be validated in the second independent cohort of patients. Acknowledgements Grant support of IGA -Ministry of Health of the Czech Republic NT/12438-4. Disclosure of Interest None Declared

Background Increased serum levels of B cell activating factor (BAFF) have been detected in patients with idiopathic inflammatory myopathies (IIM) [1], which in anti-Jo-1 positive patients correlate with serum autoantibody concentration. The correlation of BAFF expression with disease activity in IIM patients has recently been described. Objectives To investigate serum BAFF levels in anti-PM-Scl positive patients with co-existent myositis and to assess the association with clinical disease activity in a multi-center myositis cohort. Methods Serum BAFF levels of 37 anti-PM-Scl positive IIM patients from two European countries and in 57 healthy controls were measured using ELISA. Nineteen longitudinal serum samples with corresponding clinical data were also obtained. Clinical data were derived from the Euromyositis database (www.euromyositis.eu). Results Serum levels of BAFF in anti-PM-Scl positive PM/DM patients were significantly higher compared to healthy controls (P=0.008) , but there was no statistically significant difference between PM or DM patients (P>0.05) . BAFF levels correlated with both muscular (r=0.509, P=0.002) and extramuscular disease activity (r=0.487, P=0.003). There was a negative correlation with manual muscle test (MMT8) results - increased muscle weakness thus correlated with increased serum BAFF levels (r=-0.423, P=0.025) . The composite disease activity (DA) scores MITAX and MYOACT correlated positively with BAFF levels; MITAX: r=0.374, P=0.027 ; MYOACT: r=0.430, P=0.010. There was a correlation with disease activity (DA) of various systems: Constitutional DA (r=0.382, P=0.023) , Cutaneous DA (r=0.471, P=0.004) , Gastrointestinal DA (r=0.545, P=0.001) and Pulmonary DA (r=0.524, P=0.001) . Furthermore, longitudinal change (∆) in BAFF levels correlated with ∆Physician Global DA (r = 0.6834, P = 0.0035) , ∆Muscular DA (r=0.786, P , and ∆MITAX Score (r=0.672, P=0.002) . Change in BAFF correlated significantly also with ∆MYOACT (r=0.698, P=0.001) and with its components: ∆Cutaneous DA (r=0.491, P=0.033) , ∆Skeletal DA (r=0.588, P=0.008) , ∆Gastrointestinal DA (r=0.548, P=0.015) , ∆Pulmonary DA (r=0.491, P=0.039) and ∆Cardiovascular DA (r=0.471, P=0.042) . Conclusions Serum levels of BAFF are increased in anti-PM-Scl positive patients with IIM, where BAFF levels correlate with clinical disease activity assessments. Furthermore, longitudinal changes in BAFF levels over time also correlate with changes in disease activity measures. These findings indicate that BAFF is likely implicated in the pathogenesis of PM/DM. BAFF is thus a potential biomarker in IIM. References O Krystůfkova, T Vallerskog, S Barbasso Helmers, H Mann, I Půtova, J Bělacek, V Malmstrom, C Trollmo, J Vencovský, I E Lundberg, Increased serum levels of B cell activating factor (BAFF) in subsets of patients with idiopathic inflammatory myopathies, Ann Rheum Dis 2009;68:836-843 doi:10.1136/ard.2008.091405 Acknowledgements IGA -Ministry of Health of the Czech Republic NT/12438-4. Disclosure of Interest None Declared

Background Hydroxy-methyl-glutaryl Coenzyme-A reductase (HMGCR) inhibitors or statins are a well-acknowledged cause of a spectrum of myopathic consequences including an asymptomatic increase of creatine kinase (CK), myalgias, myositis and rhabdomyolysis. A unique autoantibody with specificity against 200-kd and 100-kd proteins has been recently associated with statin induced myositis (1) based on identification of cases with features of necrotizing myopathy. The 100kd autoantigen has been identified as HMGCR (2). We sought to further characterize cases of clinically suspected statin-induced myositis using clinical, serological and pathological data. Objectives The aim was to characterize statin induced myositis patients in a clinical setting and test the utility of the newly identified anti-200/100 autoantibody. Methods Patients with a statin induced myositis were identified from a large tertiary myositis referral centre in Salford, UK. Case records of all patients were reviewed with selected patients’ blood samples tested for anti-200/100 autoantibody. Clinical features, concomitant medications, co-morbidities, immunology, electromyography (EMG), magnetic resonance imaging (MRI) and muscle biopsies for each patient were reviewed. Results 10 patients were identified with a clinical diagnosis of statin induced myositis. Mean age of diagnosis was 59 years (70% male). Median CK level detected at onset was 1,750 IU/litre (range 28-11,984). 9/10 patients were on a lipophilic statin (simvastatin/atorvastatin) with 1 patient on a hydrophilic statin (rosuvastatin); mean daily dose of 39mg/day prior to symptom onset. 5/10 patients were on a concomitant medication known to interact with a statin (amiodarone, proton pump inhibitors, high dose vitamin D). 3/10 patients were anti-nuclear-antibody positive (2 had low titres, 1/100; 1 positive 1/1000), whilst 2 patients were anti-Ro antibody positive. 6 patients demonstrated some evidence of myositis on MRI, of which 3 patients exhibited myopathic changes on EMG. 8 patients had evidence of myopathic muscle on biopsy, 2 patients with type II fibre atrophy. Of the 7 patients tested for anti-HMGCR by Western blotting using a recombinant source, 6 tested positive. 2 patients who tested strongly 200/100 positive required immunosuppression and had biopsy features of necrosis, phagocytosis and regeneration. 2 further 200/100 positive patients (1 strong and 1 weak positive) had occasional necrotic fibres with little regenerative activity on biopsy and did not require further treatment. The remaining 2 200/100 positive patients had no features of necrosis on biopsy, one of whom required immunosuppression without corticosteroids. Conclusions EMG and MRI were non-specific in identifying patients with a statin induced myositis, whilst CK levels varied significantly in this group. A strongly positive anti-200/100 antibody in combination with a necrotizing myopathy on muscle biopsy could be useful clinically to identify which patients have an autoimmune element to their disease, hence may potentially benefit from immunosuppression. References Christopher-Stine L et al. Arthritis Rheum 2010;62(9):2757–66. Mammen AL et al. Arthritis Rheum. 2011 Mar;63(3):713-21. Acknowledgements MJ is a MRC Clinical Training Fellow funded by the North West England Medical Research Council Fellowship Scheme in Clinical Pharmacology and Therapeutics. Disclosure of Interest None Declared

Background Idiopathic inflammatory myopathies (IIM) are frequently accompanied by presence of autoantibodies. A correlation of anti-Jo-1 and anti-SRP antibody levels with disease activity and creatine kinase levels has been described. Recently a new anti-PM1α quantitative ELISA test detecting antibodies to the main epitope of PM-Scl-100 has become available. Objectives To investigate the prevalence of anti-PM1α autoantibodies and association with clinical symptoms, clinical disease activity and serum CK in a multicenter myositis cohort. Methods Two hundred and thirty eight consecutive patients with established IIM (103 DM, 99 PM, 8 JDM, 3 IBM and 25 IIM/CTD-overlap syndrome) were tested for the presence of anti PM-Scl autoantibodies by immunoblot and by immunoprecipitation. Eight additional anti-PM-Scl positive sera were also obtained. Serum levels of anti-PM1α autoantibodies were detected by ELISA kit (Dr. FOOKE Laboratorien GmbH, Neuss, DE). Clinical data were derived from the Euromyositis database (www.euromyositis.eu). Global and organ clinical disease activities were assessed by Myositis Activity Assessment Tool (MYOACT) 10 cm visual analogue scales. Results 19/238 (8%) patients (11 DM, 2 PM and 6 IIM/CTD-overlap syndrome (3 DM + SSc, 2 PM + SSc, 1 PM + SjS)) were positive for anti-PM-Scl in immunoblot, immunoprecipitation and anti-PM1α ELISA. 19 PM-Scl+ were 16/181 women and 3/57 men, average age 50.5 years (22.0 – 74.2) and average disease duration 3.0 years (0 – 11.6 years). Good agreement between detection tests was found. The most common clinical features among anti-PM-Scl positive patients were muscle weakness (96%), interstitial lung disease (77%), Raynaud’s phenomenon (69%) and mechanic’s hands (65%). One patient had a cancer. Anti-PM1α levels correlated with serum CK activity in the DM group (p=0.041, r=0.533) and with constitutional disease activity and seriousness of dysphagia in the PM group (p=0.048, r=0.768 and p=0.007, r=0.927). Furthermore longitudinal change in anti-PM1α levels correlated with HAQ scores in the whole group (p=0.016, r=0.730) and with global disease activity score in DM group (p=0.023, r=0.685), but not with other MYOACT parameters. Conclusions Anti-PM-Scl autoantibodies are detected in 8% of patients with myositis. They are more frequent in those with DM and overlap syndromes. Presence of these autoantibodies is associated with muscle weakness, ILD, Raynaud’s phenomenon and mechanic’s hands. Anti-PM1α levels correlate with serum CK levels in DM and their change is correlated with change of HAQ scores in the whole group and with MYOACT scores in DM group. This suggests that the quantitative measurement of anti-PM-1α may be a useful tool in the assessment of patients with this syndrome. Disclosure of Interest None Declared

Background and Objectives B-cell activating factor of the TNF family (BAFF) is important for B cell maturation and plays a role in (auto)antibodies production. Elevated serum levels in relation to autoantibodies were documented in patients with IIM. Promoter region of BAFF gene contains several known sites with single nucleotide polymorphism (SNPs). An association between Rs9514828 (–871 C/T) SNP and susceptibility to idiopathic trombocytopaenic purpura was shown and possible relations to systemic lupus erythematosus, rheumatoid arthritis or Sjogren’s syndrome were suggested but in IIM have not been studied yet. Here, we analysed relation of four BAFF SNPs located in the BAFF gene promoter with the development of IIM. Materials and Methods 146 patients with polymyositis (PM), 150 with dermatomyositis (DM), 11 patients with juvenile DM and 4 patients with inclusion body myositis and 103 healthy individuals were included. Four SNPs located upstream in the BAFF gene (Rs9514827 (–2841 T/C); Rs3759467 (–2704 T/C); Rs1041569 (–2701 T/A); Rs9514828 (–871 C/T)) were analysed by direct DNA sequencing. Serum levels of BAFF (s-BAFF) were evaluated using ELISA. Autoantibodies were detected with immunoprecipitation. The chi square test for analysis of alleles and genotypes associations and SNPStats software for haplotype frequency studies were used. Results Significantly higher frequency of –2701T allele was present in patients (18%) compared to healthy controls (12%) (P = 0.029; OR 1.684 (CI 95% = 1.050 – 2.699)). Additionally, increased –2841T allele (P = 0.086), –2841TT, CT genotype (P = 0.066) and –2701TT, AT genotype (P = 0.079) frequencies were observed in patients. SNPs were in strong linkage disequilibrium and formed four common haplotypes (TTAC, CTAT, TCAC, TTTT), with significantly different frequency (>9%) distributions between patients and controls (global P-value Conclusions We describe significant association of SNP (Rs1041569) with myositis and a relation of SNP (Rs3759467) to presence of anti-Jo-1 autoantibodies and s-BAFF levels. These results should be confirmed in an independent cohort of patients and possible relations of s-BAFF levels with disease activity and treatment should be considered. Acknowledgement IGA -Ministry of Health of the Czech Republic NT/12438–4.

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.