Subclassifying patients according to autoantibody profile may be a new way forward to get a better understanding of patterns of variation in IIM and their disease mechanisms. However, the role of autoantibodies in the pathogenesis in IIMs as well as their use as a prognostic marker still needs to be determined.
Conventional clinical techniques, including muscle strength tests, serum levels of serum creatine kinase activity and electromyography, cannot reliably differentiate between IIM and other myopathies. Even muscle biopsy lacks sensitivity and specificity [3. Targoff et al., 1997]. Therefore autoantibodies could be an important tool for such purpose.
Myositis specific autoantibodies
Autoantibodies are detected in up to 80% of polymyositis and dermatomyositis patients. Some are almost exclusively found in myositis patients, so-called myositis-specific autoantibodies (MSAs), and others are also found in other autoimmune diseases, so-called myositis associated autoantibodies (MAAs) such as anti-U1-hnRNP, anti-PM/Scl or anti-Ro [4. Hengstman et al., 2004]. Although 50% of IIM patients have defined autoantibodies (MSAs or MAAs), 70% of patient sera have been reported to contain antibodies that bound to human myocytes, implying that at least a further 20% have as yet unidentified autoantibodies [5. Stuhlmuller et al., 1996]. A number of putative MSAs have been reported in small cohort studies but most of these specificities have yet to be validated in larger cohorts or correlated to other risk factors such as genetics.
Interestingly, the MSAs are often associated with distinct clinical phenotypes. Thus the most prevalent MSAs, the anti-tRNA synthetase antibodies, of which anti-histidyl RNA synthetase (anti-Jo-1) is the most common and found in 20-30% of myositis patients, is associated with the anti-synthetase syndrome with distinct clinical manifestations including myositis, interstitial lung disease, arthritis, Raynaud´s phenomenon and skin rash on the hands, so called mechanic’s hands (Figure 2) [6. Targoff, 2000; 7. Marie et al., 2002]. Accumulating data suggest that antihistidyl tRNA synthetase antibodies may have a role in the disease mechanisms. Anti-Jo-1 antibodies may occur years before onset of clinical symptoms and sera from patients with anti-Jo-1 antibodies may activate the type I interferon system and the B cell activating factor (BAFF) [11. Miller et al., 1990; 12. Eloranta et al., 2007; 13. Krystufkova et al., 2009].
Anti-Mi-2 antibodies are associated with typical dermatomyositis skin rash (Figure 2): heliotrope exanthema and Gottron´s papules and anti-SRP antibodies are associated with a necrotising myopathy which seems to be fairly resistant to therapy [8. Miller et al., 2002; 9.Kao et al., 2004].
The presence of autoantibodies in myositis offers the most compelling evidence to date for the role of aberrant adaptive immunity in IIM, although the specific antigens that are the target of the immune reactions are still unknown. One feature of the autoantibody response within myositis is that it is usually confined to a single antigenic target within a single patient. Although ubiquitously expressed, the target antigens may be up-regulated and/or modified in regenerating, apoptotic or de-differentiated muscle tissue [10. Casciola-Rosen et al., 2005]. A non-specific muscle injury might trigger this autoimmune response, which leads to myositis. Cross-reactivity with cancer neo-antigens might explain how muscle becomes a secondary target of immune attack in cancer-associated myositis.