Study of Clara cell 16, KL-6, and surfactant protein-D in serum as disease markers in pulmonary sarcoidosis

Chest. 2003 Dec;124(6):2119-25. doi: 10.1378/chest.124.6.2119.


Study objectives: To determine the discriminative value of serum Clara cell 16 (CC16), KL-6, and surfactant protein (SP)-D as markers of interstitial lung diseases, and their ability to reflect pulmonary disease severity and prognosis in sarcoidosis.

Subjects: Seventy-nine patients with sarcoidosis and 38 control subjects.

Measurements: Serum CC16, KL-6, and SP-D concentrations at disease presentation were measured. Pulmonary function tests and chest radiographs were analyzed at presentation and 2-year follow-up.

Results: All markers co-correlated, and a significant difference was found between CC16, KL-6 (Krebs von den Lungen-6), and SP-D levels in patients with sarcoidosis and control subjects (p < 0.0001). Receiver operating characteristic curve analysis revealed largest area under the curve for KL-6. Significantly higher levels of CC16 and KL-6 were found in patients with parenchymal infiltration (stage II, III) compared to patients without parenchymal infiltration (stage I). In concordance, CC16 and KL-6 levels inversely correlated with diffusion capacity and total lung capacity, and KL-6 also with inspiratory vital capacity. Moreover, higher KL-6 levels were weakly but significantly associated with persistence or progression of parenchymal infiltrates at 2-year follow-up.

Conclusion: In this study, KL-6 appears to be the best discriminative marker in differentiating patients with sarcoidosis from healthy control subjects; however, as it is not a specific marker for this condition, this quality is unlikely to be useful as a diagnostic tool. Both CC16 and KL-6 may be of value in reflecting disease severity, and KL-6 tends to associate with pulmonary disease outcome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens / blood*
  • Antigens, Neoplasm
  • Biomarkers
  • Case-Control Studies
  • Enzyme Inhibitors / blood*
  • Female
  • Glycoproteins / blood*
  • Humans
  • Male
  • Middle Aged
  • Mucin-1
  • Mucins
  • Proteins / metabolism*
  • ROC Curve
  • Radiography
  • Sarcoidosis, Pulmonary / blood*
  • Sarcoidosis, Pulmonary / classification
  • Sarcoidosis, Pulmonary / diagnostic imaging
  • Severity of Illness Index
  • Smoking / adverse effects
  • Uteroglobin*


  • Antigens
  • Antigens, Neoplasm
  • Biomarkers
  • Enzyme Inhibitors
  • Glycoproteins
  • MUC1 protein, human
  • Mucin-1
  • Mucins
  • Proteins
  • SCGB1A1 protein, human
  • Uteroglobin