The idiopathic inflammatory myopathies (IIMs) poly-myositis (PM) and dermatomyositis (DM) are heterogeneous conditions that are historically diagnosed by proximal muscle weakness, evidence of muscle inflammation or necrosis, and characteristic skin lesions [1
]. However, it is now well recognized that patients can present with other overlapping features, including arthritis and systemic involvement (including interstitial lung disease, or ILD), and this has led to the proposal of alternative diagnostic criteria [3
]. In recent years, it has become even more apparent that autoantibodies have a role in distinguishing between further subtypes of myositis patients, and clinico-serological classifications have been proposed. The myositis autoantibodies can be divided into myositis-associated autoantibodies (MAAs) and myositis-specific autoantibodies (MSAs). The MAAs - anti-PMScl, anti-Ku, anti- U1RNP, and anti-U3RNP (fibrillarin) - are commonly found in myositis patients who have features of other connective tissue diseases (CTDs) (in particular, overlap with systemic sclerosis). In contrast, the MSAs are found exclusively in IIM and are directed to specific proteins found in both the nuclear and cytoplasmic regions of the cell; these MSAs correlate with genotype and clinical manifestations [4
]. Investigations into these specific autoantibodies help classify myositis patients into increasingly homogeneous subgroups, may guide specific treatment regimes, and importantly increase our understanding of the pathogenesis of IIM.
The 'traditional' MSAs - anti-Jo-1 (and the less common non-Jo-1 anti-synthetases), anti-SRP, and anti-Mi-2 - can be detected by routine commercial assays and are identified in approximately 40% to 50% of adult myositis patients and in less than 10% of juvenile dermatomyositis (JDM) patients [6
]. More recently, a number of groups have reported the identification of novel MSAs, including anti-p155/140, anti-SAE, anti-CADM-140 (melanoma differentiation-associated gene 5, or MDA5), anti-p140, and anti-200/100, the clinical and genetic associations of which are described in this review. With the inclusion of the latter MSAs, it is now possible to identify a positive MAA or MSA in approximately 80% of myositis patients, allowing a clearer serological stratification of patients (Table and Figure ).
Myositis-specific autoantibodies, target autoantigens, and clinical associations
Figure 1 Immunoprecipitation of myositis-specific autoantibodies. Ten percent SDS-PAGE of immunoprecipitates of [35S] labeled K562 cell extract. Lane 1: normal serum; lane 2: anti-PL7; lane 3: anti-PL12; lane 4: anti-Zo; lane 5: anti-Jo-1; lane 6: anti-OJ; lane (more ...)