Profiling Autoantibodies in Idiopathic Inflammatory Myopathies

Abstract Objects To screen autoantibodies (autoAbs) in sera of Idiopathic Inflammatory Myositis (IIM) patients and to assess their clinical significance for diagnosis, classification and disease activity evaluation. Methods IgG and IgM autoAbs were comprehensively profiled from 138 IIM patients, 70 SLE, 50 SSc and 100 normal controls (NC) using a customized autoantigen array bearing 125 myositis-specific antigens (MSA) and other autoantigens. Western blot and Immunoprecipitation were used for autoAb verification. The profile of autoAbs and correlation with clinical criteria were evaluated. Results 78% IIM patients showed positive reactivity to at least 1 MSA. The autoAbs which exhibited high prevalence in IIM are anti- Jo-1 (24.6%), MDA5 (23.2%), SAE2 (13%), SRP54 (11.6%) and DNA polymerase II (8.7%). We identified the autoAb clusters that best distinguish the 3 autoimmune disease: anti-Jo-1 and anti-MDA5 for IIM, and anti-CENP-A&B and Scl-70 for SSc, and anti-chromatin/Nucleosome, anti-dsDNA, and anti-Sm/SmD for SLE. The coexistence of MSA autoAbs was observed in IIM with about 35% IIM patients carried more than 2 MSA autoAbs. The IIM patients who developed interstitial lung disease (ILD) exhibited significantly higher autoAbs against Jo-1, MDA5, Mi-2, Ro-SSA and Trptophanyl compared with the IIM without ILD (<0.05). The IIM patients who carried positive autoAbs against JS, TIF1γ, Mitochondrial antigen and La/SSB showed a significantly higher risk of malignancy (p<0.05). Based on autoAbs, we established an autoAb score for IIM prediction and evaluation. Conclusion Autoantibody profiling revealed distinct and heterogenic autoAbs in IIM which are potential biomarker for diagnosis, prognosis and classification of the disease.