Multiparameter Autoantibody Detection Aids Diagnosis of Myositis

Idiopathic inflammatory myopathies (IIM), or myositides, are a collection of systemic autoimmune rheumatic diseases. These disorders are characterized by chronic inflammation of the skeletal muscle, and in some instances, can be linked to cancer. Due to their rarity, resemblance to other rheumatic diseases, and the potential for overlap syndromes, diagnosing IIMs can be complex. Pinpointing the exact subtype of the disease is crucial due to diverse treatment options. Autoantibodies are critical diagnostic biomarkers for IIM and help in identifying disease subtypes. The German Society for Neurology (DGN) issued guidelines in 2022, mandating the identification of myositis-specific autoantibodies (MSA) and myositis-associated autoantibodies (MAA) as a diagnostic step. Given the low prevalence and frequent isolation of IIM autoantibodies, antibody detection must be as comprehensive as possible.

EUROIMMUN (Lübeck, Germany) has developed a line blot (EUROLINE Autoimmune Inflammatory Myopathies 20 Ag Profile) that uniquely combines 20 nuclear and cytoplasmic antigens. This assists in detecting and differentiating autoantibodies in IIM, making it the most comprehensive commercially available line blot for IIM diagnostics. The antigen portfolio encompasses the MSA target antigens Zo, Ks, Ha, cN-1A, OJ, EJ, PL-12, PL-7, SRP, Jo-1, SAE1, NXP2, MDA5, TIF1γ, Mi-2α and Mi-2β and the MAA target antigens Ku, PM-Scl75, PM-Scl100 and Ro-52, each printed onto separate membrane chips for optimal antibody detection efficiency. The immunoblot analysis is particularly effective in identifying autoantibodies against cytoplasmic antigens, which other methods such as indirect immunofluorescence can miss. The assay process and result evaluation can be fully automated.

This specific antibody detection approach aids in diagnosing IIM subforms in light of clinical symptoms. Notably, anti-cN-1A is the sole known serological marker for sporadic inclusion body myositis (sIBM). Since anti-cN-1A is rarely found in other IIMs, its detection can help distinguish sIBM from other IIM forms, aiding in early diagnosis. The EUROLINE is the sole commercial line blot that includes this antigen. The antigens Zo, Ks, and Ha supplement the tRNA synthetase antigen spectrum for differential diagnosis of anti-synthetase syndrome (ASS) along with EJ, OJ, PL-12, PL-7, Jo-1, and SRP. Current research is exploring the link of antibodies against Zo, Ks, and Ha with interstitial lung disease. Autoantibodies against Mi-2α, Mi-2β, NXP2, TIF1γ, SAE1, and MDA5 are indicative of dermatomyositis (DM), with anti-NXP2 and anti-TIF1γ often associated with malignancies. Antibodies against Ku, PM-Scl-75, and PM-Scl100 are typically found in overlap syndromes, while anti-SRP is present in necrotizing myositis. Detecting specific autoantibodies can significantly accelerate diagnosis, enabling prompt therapeutic intervention. Autoantibody profiling also helps in assessing malignancy risk and predicting therapy outcomes.

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