Serum Levels of Caspase-Cleaved Cytokeratin-18 in Interstitial Lung Disease Associated with Rheumatoid Arthritis, Dermatomyositis, and Polymyositis

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  • Kawasaki Tatsuya
    Division of Rheumatology and Allergology, Department of Internal Medicine, St. Marianna University School of Medicine
  • Imamura Mitsuru
    Division of Rheumatology and Allergology, Department of Internal Medicine, St. Marianna University School of Medicine
  • Nagafuchi Hiroko
    Division of Rheumatology and Allergology, Department of Internal Medicine, St. Marianna University School of Medicine
  • Suzuki Shotaro
    Division of Rheumatology and Allergology, Department of Internal Medicine, St. Marianna University School of Medicine
  • Mouri Mariko
    Division of Rheumatology and Allergology, Department of Internal Medicine, St. Marianna University School of Medicine
  • Ishizaki Yoshiki
    Division of Rheumatology and Allergology, Department of Internal Medicine, St. Marianna University School of Medicine
  • Sakurai Keiichi
    Division of Rheumatology and Allergology, Department of Internal Medicine, St. Marianna University School of Medicine
  • Mizushima Machiko
    Division of Rheumatology and Allergology, Department of Internal Medicine, St. Marianna University School of Medicine
  • Tonooka Kumiko
    Division of Rheumatology and Allergology, Department of Internal Medicine, St. Marianna University School of Medicine
  • Takakuwa Yukiko
    Division of Rheumatology and Allergology, Department of Internal Medicine, St. Marianna University School of Medicine
  • Ooka Seido
    Division of Rheumatology and Allergology, Department of Internal Medicine, St. Marianna University School of Medicine
  • Sugihara Takahiko
    Division of Rheumatology and Allergology, Department of Internal Medicine, St. Marianna University School of Medicine
  • Kawahata Kimito
    Division of Rheumatology and Allergology, Department of Internal Medicine, St. Marianna University School of Medicine

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<p>Purpose: Although the detailed pathogenesis of interstitial lung disease (ILD) is unknown, the involvement of apoptosis has been suggested. We investigated whether the apoptosis marker of epithelial cells in serum can be a marker of disease activity, to examine the involvement of apoptosis in the pathology of ILD associated with connective tissue disease (CTD).</p><p>Methods: We analyzed serum levels of caspase-cleaved cytokeratin-18 (M30) in 87 patients, consisting of 52 patients with rheumatoid arthritis (RA) and 35 with polymyositis or dermatomyositis (PM/DM), using enzyme-linked immunosorbent assays. Of the 87 patients, 39 (17 with RA and 22 with PM/DM) had ILD.</p><p>Results: The median (interquartile range) serum level of M30 was 283.2 (153.9-340.6) U/L in the patients with ILD associated with RA and PM/DM (RA-ILD, and PM/DM-ILD), and 143.4 (108.5-176.2) U/L in the patient without ILD. Serum level of M30 was significantly higher in patients with RA-ILD than those with RA without ILD (P＜0.001). Furthermore, serum level of M30 was significantly higher in patients with PM/DM-ILD than those with PM/DM without ILD (P＜0.001). Serum M30 levels were negatively correlated with percent-predicted forced vital capacity (rs=-0.37). The cutoff value of serum M30 to detect CTD-ILD, revealed by receiver-operating characteristic curve analysis, was 211.7 U/L, with a sensitivity of 85.4% and specificity of 66.7%.</p><p>Conclusion: Lung apoptosis is suggested to be involved in the fibrosis of CTD-ILD. The serum M30 level can be useful as a detection and activity marker for CTD-ILD.</p>

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