The Role of Myositis-Specific Autoantibodies in the Dermatomyositis Spectrum

Abstract

Dermatomyositis (DM) is a systemic autoimmune disease that affects skeletal muscles, the skin, and the lungs. It is characterized by autoantibodies, tissue inflammation, parenchymal cell damage, death, and vasculopathy. In terms of epidemiology, DM affects both children and adults. The current pathophysiology of DM is described as an autoimmune attack on the afflicted organs driven by environmental variables such as UV exposure, medications, infections, and lifestyle choices in genetically predisposed people. DM is also a paraneoplastic condition, which means that cancer may arise before, along with, or following the development of the symptoms of DM.Myositis-specific autoantibodies are associated with phenotypical features and are used for subclassification of dermatomyositis patients. Because the risk of interstitial lung disease (ILD), internal malignancy, destructive disease trajectory, and maybe a response to medication differs by DM myositisspecific antibody (MSA) group, a better knowledge of MSAs and the validation and standardization of tests employed for detection is crucial for improving diagnosis and treatment. The diagnostic sensitivity and specificity of tests for various MSAs are not ideal, just like with any other test. However, more antibody tests are anticipated to make their way into formal schemata for diagnosis and actionable risk assessment in DM due to worldwide standardization and more extensive research. In this review, we outline crucial aspects for interpreting clinical and pathologic relationships with MSA in DM and critical knowledge and practice gaps that will optimize the clinical benefit and utility of MSAs as diagnostic and prognostic markers.

Paraneoplastic Neurologic Syndromes

“…Notably, anti-transcription intermediary factor-γ antibodies in those under 40 years old appear to imply no increased risk of malignancy, but the same antibody in a patient over 50 years old implies a higher risk of associated malignancy. 71 Seronegative necrotizing autoimmune myopathy may also be associated with occult malignancy. Whole-body MRI has been studied to help diagnose and fully characterize the extent of the various paraneoplastic myopathic syndromes prior to biopsy and serologic test results and may have the added benefit of simultaneously screening for underlying tumors and signs of associated collagen vascular diseases and avascular necrosis, which are common in these patients.…”

“…A variety of antibodies have been described in dermatomyositis, and anti–nuclear matrix protein 2, anti–melanoma differentiation-associated protein 5, and anti–transcription intermediary factor-γ antibodies have been associated with an increased risk of underlying malignancy. Notably, anti–transcription intermediary factor-γ antibodies in those under 40 years old appear to imply no increased risk of malignancy, but the same antibody in a patient over 50 years old implies a higher risk of associated malignancy 71 . Seronegative necrotizing autoimmune myopathy may also be associated with occult malignancy.…”

Unmet Medical Needs in Chronic, Non-communicable Inflammatory Skin Diseases

“…Thorough characterization of the autoantibody response in DM patients is also important in this regard, as certain autoantibodies are associated with a high risk of cancer ( 342 ). In addition, a detailed characterization of the autoantibody response in DM also allows to differentiate organ involvement and prognosis ( 343 ). In summary, missing awareness, lack of definite diagnostic criteria and no evidence-based recommendation for cancer screening are diagnostic challenges in DM.…”

Trichoscopic, oral, and periungual fold findings as activity and damage markers in dermatomyositis patients and their correlation with myositis antibodies

“…The presence of these Abs correlates with distinct clinical manifestations, malignancy, and interstitial lung disease, and are predictive of organ manifestations and potentially of prognosis. Anti-TIF1g, Anti-MDA5, and Anti-SAE1/2 are MSAs associated with severe cutaneous involvement in DM, and Anti-Mi2a, Anti-Mi2b, Anti-NPX2, and Anti-SAE1/2 are MSAs associated with intense muscle involvement in DM [1,2,[17][18][19][20][21].…”