Multicenter Clinical Comparison Between Anti-NXP2 and Anti-TIF1-γ Antibody-Positive Myositis, and Analysis of the Clinical Significance of Anti-NXP2 Antibody Titers in Idiopathic Inflammatory Myopathies.

We aimed to measure anti-nuclear matrix protein 2 antibody (anti-NXP2) titers in patients with anti-NXP2-positive idiopathic inflammatory myopathies, investigate whether these titers are associated with clinical manifestations, malignancy risk, and treatment response, and compare the clinical and serological features between anti-NXP2-positive and anti-transcriptional intermediary factor 1-γ antibody (anti-TIF1-γ)-positive dermatomyositis in order to identify practical indicators for differentiating the two subsets. We established a newly optimized in-house enzyme-linked immunosorbent assay for the quantitative measurement of anti-NXP2. After excluding two of the 34 initially identified patients with anti-NXP2 antibody reactivity, we used the assay to analyse sera from 32 patients with anti-NXP2-positive idiopathic inflammatory myopathy. Clinical correlations between anti-NXP2 titers and inflammatory indices, cardiothoracic ratio, malignancy status, and longitudinal changes after immunosuppressive therapy were examined. We developed a novel clinical scoring system to differentiate between anti-NXP2-positive and anti-TIF1-γ-positive myositis. The anti-TIF1-γ-positive patients showed a higher frequency of classic dermatomyositis skin manifestations, whereas the anti-NXP2-positive patients had significantly higher creatine kinase, aldolase, and lactate dehydrogenase levels, indicating more prominent muscle involvement. Anti-NXP2 titers correlated with erythrocyte sedimentation rate and cardiothoracic ratio and were significantly higher in patients with malignancy in the anti-NXP2-positive idiopathic inflammatory myopathy patients. Longitudinal analyses demonstrated declines in antibody titers after immunosuppressive treatment. Our scoring system, incorporating age at onset, Gottron's sign, creatine kinase, lactate dehydrogenase, and malignancy status, highly accurately distinguished between anti-NXP2-positive and anti-TIF1-γ-positive myositis. Anti-NXP2 titers reflect systemic inflammation, cardiac involvement, and malignancy risk in anti-NXP2-positive idiopathic inflammatory myopathy. The observed decline in anti-NXP2 titers after therapy suggests the potential utility of these titers as biomarkers for longitudinal disease assessment and stratifying malignancy risk.