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Myositis Autoantibodies

Idiopathic inflammatory myositis, including polymyositis and dermatomyositis (PM/DM), are systemic inflammatory disorders that involve the skin, lung and muscle. A number of autoantibodies can be detected in the sera of patients with PM/DM. Some are specific to PM/DM and are called myositis-specific autoantibodies while others occur in myositis overlap syndrome and are referred to as myositis-associated autoantibodies. Detection of these autoantibodies assists in determining diagnosis, prognosis and response to therapy.

Myositis specific autoantibodies include antibodies to aminoacyl-tRNA synthetases, which are the enzymes that catalyze the binding of amino acids to their corresponding tRNAs. Six different autoantibodies have been identified so far: anti-Jo-1 (histidyl), anti-PL-7 (threonyl), anti-PL-12 (alanyl), anti-EJ (glycyl), anti-OJ (isoleucyl), anti-KS (asparaginyl), anti-Zo (anti-phenylalanyl-tRNA synthetase) and anti-tyrosyl-tRNA synthetase. Anti-synthetase autoantibodies are detected in 20 to 30% of patients with inflammatory myositis. Patients with these autoantibodies share similar clinical features including myositis, interstitial lung idisease, polyarthritis, fever, Raynaud’s phenomenon and mechanic’s hand. This combination of anti-synthetase autoantibodies and clinical features is called the ‘antisynthetase syndrome’. Patients with antisynthetase autoantibodies are more likely to have interstitial lung disease at the time of diagnosis. Anti-KS, anti-PL-12 and anti-OJ antibodies may have a stronger association with interstitial lung disease than myositis.

Anti-signal recognition particle (SRP) autoantibody is present in approximately 5% of patients with PM. SRP is a cytoplasmic small RNA–protein complex that recognizes signal sequences of newly synthesized secretary proteins or membrane proteins and regulates translocation across the endoplasmic reticulum membrane.

Patients with anti-SRP antibody have acute onset of severe myositis, disability, dysphagia and highly elevated levels of serum creatine kinase. These patients are usually resistant to standard treatment with corticosteroids and show frequent exacerbation. Anti-SRP antibody appears to be a marker for severe and rapidly progressive necrotizing myopathy.

Anti-Mi-2 antibody is more common in DM than in PM. It is detected in approximately 15–20% of patients with DM. Mi-2 is a DNA helicase that is located in the nucleus and plays a role in regulation of gene transcription by histone acetylation. Many reports have suggested that anti-Mi-2 autoantibody is associated with fewer complications and relatively good prognosis.

Clinically amyopathic DM (CADM) shows the typical skin manifestations of DM but no or little evidence of clinical myositis. Asian patients with CADM frequently develop acute progressive interstitial lung disease and have poor prognosis. The myositis specific autoantibodies discussed above are usually not detected in these patients. Anti-CADM-140 antibody has been detected in some of these patients. This autoantibody recognizes the IFIH1 protein, which recognizes viral RNA and plays an important role in the innate immune response.

Anti-p155/140 autoantibody is strongly associated with DM and cancer-associated DM. The autoantibody is detected in 10 to 15% of patients with DM. Anti-155/140-positive patients have typical DM rash without interstitial lung disease. Cancer is present much more frequently in anti-155/140-positive patients than negative patients (70 vs 10%). The autoantigen recognized by anti-p155 antibody is transcriptional intermediary factor (TIF)-1?, which controls DNA transcription.

Anti-U1RNP is a myositis associated autoantibody that is primarily used as a serological marker for mixed connective tissue disease, but is also present in some cases of PM/DM and their overlap syndromes. U1RNP is a small nuclear ribonucleoprotein that functions as a spliceosome.

Anti-Ro/SS-A autoantibody is detected in various connective tissue diseases such as Sjögren’s syndrome, systemic lupus erythematosis, systemic sclerosis and inflammatory myositis. Two antigens are recognized by anti-Ro/SS-A, a 60 kDa protein (Ro60) and a 52 kDa protein (Ro52). Anti-Ro52 is more commonly associated with systemic sclerosis and myositis than anti-Ro60. Anti-Ro52 is detected in up to 37% of myositis patients and is often coexists with anti-Jo-1. Coexistence of anti-SS-A and anti-Jo-1 antibody seems to be a predictor for relatively severe interstitial lung disease in patients with myositis.

Anti-Ku is a myositis associated antibody whose clinical significance varies geographically. In the United States, anti-Ku antibody is detected mainly in systemic lupus erythematosis, while in Europe it is associated with polymyositis-systemic sclerosis overlap syndromes. Anti-Ku is associated with clinical features such as arthralgia and Raynaud’s phenomenon. Ku antigen is DNA-dependent protein kinase that plays a role in DNA repair, V(D)J recombination of T- and B-cell receptor genes and telomere maintenance.

Anti-PM-Scl antibody is detected in about 50% of patients with polymyositis-systemic sclerosis overlap syndrome and only 2% of patients with systemic sclerosis. Anti-PM-Scl-positive patients with overlap syndrome have a more benign disease course, limited cutaneous involvement and better response to corticosteroids.

In summary, myositis-specific and myositis-associated autoantibodies provide much information regarding diagnosis, prognosis and choice of treatment for patients with idiopathic inflammatory myositis.


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