Autoantibodies reactive to PEP08 are clinically related with morbidity and severity of interstitial lung disease in connective tissue diseases

Anti‐Ro52 autoantibodies (Ro52‐autoAbs) appear in the sera of connective tissue disease (CTD) patients with interstitial lung disease (ILD). Studies using patient sera have shown a correlation between the generation of Ro52‐autoAbs and the clinical morbidity and severity of CTD with ILD. In this study, we used a single B‐cell manipulating technology and obtained 12 different monoclonal Ro52‐autoAbs (mRo52‐autoAbs) from the selected four patients suffering from severe ILD with a high titer of Ro52‐autoAbs in their sera. Western blot analysis revealed that 11 of 12 mRo52‐autoAbs bound to the coiled‐coil domain of Ro52. Competitive ELISA demonstrated that mRo52‐autoAbs competed with each other to bind to Ro52. Epitope mapping showed that two of them specifically bound to a peptide (PEP08) in the coiled‐coil domain. We then examined the titer of Ro52‐autoAbs in the sera of 192 CTD patients and assessed the relationship between the serum levels of Ro52‐autoAbs that were reactive to PEP08 peptide and the clinical morbidity and severity of ILD. Statistical analysis revealed that the production of PEP08‐reactive Ro52‐autoAbs correlated with the morbidity and severity of ILD in CTD. Assessment of the production of PEP08‐reactive Ro52‐autoAbs in autoimmune diseases is useful for predicting the clinical morbidity of ILD.