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Objectives To determine prevalence and co-existence of myositis specific autoantibodies (MSAs) and myositis associated autoantibodies (MAAs) and associated clinical characteristics in a large cohort of idiopathic inflammatory myopathy (IIM) patients. Methods Adult patients with confirmed IIM recruited to the EuroMyositis registry (n = 1637) from four centres were investigated for the presence of MSAs/MAAs by radiolabelled-immunoprecipitation, with confirmation of anti-MDA5 and anti-NXP2 by ELISA. Clinical associations for each autoantibody were calculated for 1483 patients with a single or no known autoantibody by global linear regression modelling. Results MSAs/MAAs were found in 61.5% of patients, with 84.7% of autoantibody positive patients having a sole specificity, and only three cases (0.2%) having more than one MSA. The most frequently detected autoantibody was anti-Jo-1 (18.7%), with a further 21 specificities each found in 0.2–7.9% of patients. Autoantibodies to Mi-2, SAE, TIF1, NXP2, MDA5, PMScl and the non-Jo-1 tRNA-synthetases were strongly associated (p, Highlights • Myositis specific autoantibodies very rarely coexist in the one individual allowing endotypes to be more precisely defined. • The association of anti-TIF1 and cancer-associated myositis is confirmed with a cut-off age of over 58 years. • In a large combined European myositis cohort associations of anti-SRP with carditis and anti-Mi-2 with cancer have emerged. • Myositis associated autoantibodies are strongly associated with having myositis in association with another connective tissue disease.

Introduction ILD represents a heterogeneous spectrum of subgroups, the biggest being IPF and connective tissue disease ILD (CTD-ILD). In IPF, a lack of biomarkers and the dangers of lung biopsy make the diagnosis dependant on HRCT. Usual Interstitial Pneumonia changes are typical of IPF, but can also occur in CTD-ILD, making misdiagnosis a possibility. While CTD-ILDs can respond to immunosuppression with corticosteroids and disease modifying drugs, these agents are ineffective and harmful in IPF, and therefore contraindicated (Raghu et al. N Eng J Med 2012; 366: 1968). Where possible, it is thus important to exclude a covert CTD-ILD in IPF patients. Previous studies have detected autoantibodies in 6%–38% of patients with idiopathic interstitial pneumonias (Song et al. Yonsei Med J 2015; 56: 676, Watanabe et al. Respir Med 2011; 105: 1238), but wide-ranging CTD serotyping has not been undertaken in a large UK IPF cohort. Methods The gold standard for autoantibody detection is immunoprecipitation (IP), which very occasionally detects anti-Ro, but no other, autoantibodies in normal subjects. IP of radio-labelled K562 cells was used to serotype 250 IPF patients recruited via UK-BILD. All satisfied the 2011 ATS/ERS diagnostic guidelines and had IPF-specific HRCT changes (Raghu et al. Am J Respir Crit Care Med 2011; 183: 788). Proteins recognised by autoantibodies from patients’ serum were fractionated by 9% SDS-PAGE gel, and identified by autoradiography. Known autoantigens were identified by direct comparison with antibody positive controls on the same gel. Results Four of 250 IPF patients (1.6%) were IP-positive for recognised CTD-specific autoantibodies, including one with an anti-synthetase (anti-OJ) and three with scleroderma or scleromyositis overlap-associated antibodies (anti-RNA Polymerase II, anti-PM-Scl and anti-Ku respectively). There were no clinical or radiographic characteristics which distinguished antibody positive from antibody negative cases. Conclusion Although CTD-specific autoantibodies were detected in only a tiny proportion of IPF patients, to suggest a possible misdiagnosis, this could have potentially serious therapeutic implications for individual patients. We recommend that, while IPF is clearly a robust diagnosis when made by multidisciplinary teams in tertiary centres, clinicians should endeavour to undertake comprehensive autoantibody testing in all IPF cases.

Objectives The aim was to identify and characterize all incident adult cases of idiopathic inflammatory myopathies (IIM) between 1 January 2007 and 31 December 2016 in the City of Salford, UK. Methods Adults first diagnosed with IIM within the study period were identified by: a Salford Royal NHS Foundation Trust (SRFT) inpatient episode IIM-specific ICD-10 coding search; all new patient appointments to SRFT neuromuscular outpatient clinics; and all Salford residents enrolled within the UKMYONET study. All patients with definite IIM by the 2017 EULAR/ACR classification criteria were included, as were probable cases if consensus expert opinion agreed. Cases were excluded if

Interstitial lung disease (ILD) comprises many heterogeneous disease groups, the largest being CTD-associated and those labelled as idiopathic out of necessity. The mechanisms causing ILD are poorly understood, but most CTD- and idiopathic-ILD cases can respond to immunosuppression, clearly suggesting a pathological role for inflammation. By contrast, corticosteroid immunosuppression causes harm without benefit in the feared idiopathic pulmonary fibrosis, suggesting that inflammation plays little pathological role, and where ILD progresses rapidly to lethal outcome even with anti-fibrotic drug use. Given the treatment response differences apparent between ILD subgroups, and the dangers and costs of corticosteroid and anti-fibrotic drug use, respectively, it has become vital in every ILD patient to make an accurate subgroup diagnosis, to optimize treatment selections. This review discusses why differentiating CTD- and idiopathic-ILD subgroup cases remains so problematic, and why existing comprehensive CTD-specific serology would, if generally available, represent an ideal biomarker tool to enhance ILD subgroup diagnostic accuracy.

Background The idiopathic inflammatory myopathies (IIM) are a group of autoimmune mediated disorders characterised by skeletal muscle inflammation. Identification of factors associated with mortality may allow future interventional measures to reduce mortality. Objectives To compare mortality rates in a large UK IIM population with those in the general population and to identify clinical, serological and demographic factors associated with mortality. Methods IIM patients were identified through the UKMYONET study from 84 UK centres. Patients with adult-onset probable or definite polymyositis (PM) or dermatomyositis (DM), or defined inclusion body myositis (IBM) as per accepted criteria (Bohan/Peter, Griggs, MRC) were recruited. Data included demographics, smoking status, cancer diagnosis, clinical features and presence of myositis-specific/associated antibodies (MSA/MAA). Date and cause of death was collated from the UK Health and Social Care Information Service. Age-standardised mortality rates (ASR) per 100,000 persons were calculated for each gender and IIM subtype. Mortality was compared between IIM subtypes (PM as a reference), clinical features and MSA/MAA subsets using calculated hazard ratios (HRs), adjusted for age, sex and smoking. Results 724 IIM patients were recruited (62.2% female, 34% smoked, mean age of disease onset 52.4 years [SD 14.9]). Mean symptom onset to diagnosis time was 1.3 years (SD 2.5). 72 (10%) had died at time of analysis. Median time from diagnosis to death for the whole cohort was 12 years (1st quartile 4 years, 3rd quartile 17 years), 8 years for the cancer-associated myositis (CAM) cohort and 16 years for the non-CAM cohort. Mortality risk did not vary between men and women: 10.2% vs 9.8%, p=0.9. 31 deaths were due to pneumonia, 2 interstitial lung disease (ILD), 1 pulmonary embolism, 16 cardiac causes (myocardial infarction, cardiac failure), 11 malignancy, 8 sepsis, 2 IIM and 1 spontaneous haemothorax. Increasing age at onset and smoking history were associated with mortality: HR 1.1 (95% CI 1.1, 1.2) and 2.3 (1.4, 3.8) respectively. Cardiovascular pathology was associated with higher mortality: HR 3.5 (1.2, 10.4). Periorbital oedema was associated with higher mortality in the DM group: HR 6.7 (1.5, 31.5). Table 1 shows that ASRs per 100,000 persons were more than seven times higher than those in the general UK population: ASR 7559 vs 987/100,000 persons respectively. IBM ASR was significantly lower than DM and PM for females only. CAM was significantly associated with mortality in men only: HR 5.7 (95% CI 2.5, 13.1). No other IIM subtype, clinical feature (including ILD) or MSA/MAA subsets (including Jo-1) were associated with mortality. Conclusions This is the first study to investigate factors associated with increased mortality in a large UK IIM population with a verified IIM diagnosis. Mortality rates in IIM are higher than those of the general UK population mainly due to cardiovascular pathology and cancer, with pneumonia being the leading cause of death. Disclosure of Interest None declared