Last updated: October 9, 2014
Synonym: Anti-synthetase antibodies
Description: Approximately 60% to 80% of patients with inflammatory myopathies have autoantibodies. Some of these, such as ANAs, are seen in other syndromes and are not specifically associated with muscle disorders. However, approximately half of patients with autoantibodies show antibody specificities that are exclusively seen in association with inflammatory muscle disease. Most myositis-specific autoantibodies (MSAs) are directed against intracellular (usually cytoplasmic) ribonucleoproteins that are involved in protein translation. The most common are a family of antibodies directed against aminoacyl-tRNA synthetases. Antibodies to histidyl-tRNA, also called Jo-1 antibodies, are the most common and most clinically assayed of these antisynthetase antibodies. Other MSAs include anti–Mi-2 and anti–signal-recognition particle antibodies.
Method: MSAs are detected by indirect fluorescent antibody assay.
Normal Values: MSAs are normally not present.
Clinical Associations: Some researchers suggest that MSAs may be more useful in defining clinical subsets of inflammatory muscle disorders than currently used clinical categories, such as polymyositis and dermatomyositis. This proposal is based on observations indicating that the clinical disease course, including mortality rates, is correlated with the pattern of autoantibody expression. Some of these clinical associations are summarized in Table 14.
—Jo-1: Jo-1 is seen in patients with polymyositis, interstitial lung disease, and arthritis; 20% of all patients with inflammatory myositis are Jo-1 positive. Patients with antibodies to synthetases have a higher incidence of interstitial lung disease than patients in the other groups; responses to treatment interventions are intermediate. The “antisynthetase syndrome” is characterized by the occurrence of inflammatory myositis, arthritis, interstitial lung disease, Raynaud’s phenomenon, photosensitive facial rashes, “mechanics (or machinists) hands” (cracked, fissured, hypertrophic changes over the distal fingers), and fever.
—Mi-2: Antibodies to Mi-2 are seen almost exclusively in patients with the clinical syndrome of dermatomyositis. These patients tend to respond best to treatment.
—Signal-Recognition Particle (SRP): Patients with antibodies to SRP tend to have the clinical syndrome of acute onset polymyositis without a rash, have variable cardiac involvement, and generally respond poorly to treatment. Limited studies in children suggest a similar clinical pattern in juvenile myositis syndromes.
|Table 14: Syndromes Associated with Myositis-Specific Autoantibodies|
|Autoantibody||Characteristic Clinical Features||Response to Treatment|
|Anti-Jo-1 and other antisynthetases||Relatively acute onset; frequent interstitial lung disease, fever, arthritis, Raynaud phenomenon||Moderate response to therapy but persistent disease|
|Anti-Signal recognition particle||Very acute onset, severe weakness, palpitations (no rash)||Poor response to therapy|
|Anti-Mi-2||Relatively acute onset, classic dermatomyositis rash, cuticular overgrowth||Good response to therapy|
Indications: MSA assays are primarily used in research to characterize subsets of inflammatory myositis. The utility of antisynthetase antibodies has largely been investigated at tertiary academic sites, and it is unknown whether the same associations will be seen in a primary care practice setting. Because MSAs are relatively expensive, not readily available, and of uncertain prognostic value, their routine in patients with myositis is not recommended.
Cost: Jo-1, $120–150; Mi-2, $170–220.
Hengstman GJ, van Engelen BG, Vree Egberts WT, et al. Myositis-specific autoantibodies: overview and recent developments. Curr Opin Rheumatol 2001;13:476–482. PMID: 11698723
Targoff IN. Laboratory testing in the diagnosis and management of idiopathic inflammatory myopathies. Rheum Dis Clin North Am 2002;28:859–890. PMID: 12506776