The idiopathic inflammatory myopathies are characterized by muscle weakness, skin disease and internal organ involvement. Autoimmunity is known to have a role in myositis pathogenesis, and myositis‐specific autoantibodies, targeting important intracellular proteins, are regarded as key biomarkers aiding in the diagnosis of patients. In recent years, a number of novel myositis autoantibodies including anti‐TIF1, anti‐NXP2, anti‐MDA5, anti‐SAE, anti‐HMGCR and anti‐cN1A have been identified in both adult and juvenile patients. These autoantibodies correlate with distinct clinical manifestations and importantly are found in inclusion body, statin‐induced, clinically amyopathic and juvenile groups of myositis patients, previously believed to be mainly autoantibody negative. In this review, we will describe the main myositis‐specific and myositis‐associated autoantibodies and their frequencies and clinical associations across different ages and ethnic groups. We will also discuss preliminary studies investigating correlations between specific myositis autoantibody titres and clinical markers of disease course, collectively demonstrating the utility of myositis autoantibodies as both diagnostic and prognostic markers of disease.

The idiopathic inflammatory myopathies (IIMs)--DM and PM--have been historically defined by broad clinical and pathological criteria. These conditions affect both adults and children with clinical features including muscle weakness, skin disease, internal organ involvement and an association with cancer in adults. Using a clinico-serological approach, DM and PM can be defined into more homogeneous subsets. Over the last few years, myositis-specific autoantibodies (MSAs) have been better characterized including autoantibodies directed against the aminoacyl tRNA-synthetase enzymes, the signal-recognition particle and the Mi-2 protein. In addition, clinically significant novel autoantibodies--anti-CADM-140, anti-SAE (small ubiquitin-like modifier activating enzyme), anti-p155/140 and anti-p140--have been described in the adult and juvenile disease spectrum. MSAs are directed against cytoplasmic or nuclear components involved in key regulatory intracellular processes including protein synthesis, translocation and gene transcription. The striking association between unique serological profiles and distinct clinical phenotypes suggests that target autoantigens may play a role in disease induction and propagation. In this review, we discuss the clinical utility and pathogenic significance of MSAs in disease expression.

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 < 0.001) with cutaneous involvement. Anti -TIF1 and anti -Mi-2 positive patients had an increased risk of malignancy (OR 4.67 and 2.50 respectively), and anti -SRP patients had a greater likelihood of cardiac involvement (OR 4.15). Interstitial lung disease was strongly associated with the anti -tRNA synthetases, anti -MDA5, and anti -U1RNP/Sm. Overlap disease was strongly associated with anti -PMScl, anti -Ku, anti -U1RNP/Sm and anti -Ro60. Absence of MSA/MAA was negatively associated with extra-muscular manifestations. Conclusions Myositis autoantibodies are present in the majority of patients with IIM and identify distinct clinical subsets. Furthermore, MSAs are nearly always mutually exclusive endorsing their credentials as valuable disease biomarkers.

Anti-p155/140 autoantibodies are clinically significant in JDM and may define a clinical subset in terms of disease severity and outcome. The same autoantigen target is detected in adult DM patients.