Chest
Volume 124, Issue 6, December 2003, Pages 2119-2125
Journal home page for Chest

Clinical Investigations
SARCOIDOSIS
Study of Clara Cell 16, KL-6, and Surfactant Protein-D in Serum as Disease Markers in Pulmonary Sarcoidosis

https://doi.org/10.1378/chest.124.6.2119Get rights and content

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.

Section snippets

Study Subjects

In this study, patients with sarcoidosis diagnosed at the Department of Pulmonology of the St. Antonius Hospital Nieuwegein between 1989 and 1999 were studied retrospectively. In all patients, the diagnosis of sarcoidosis was based on compatible clinical findings, histologic evidence of noncaseating epithelioid-cell granulomas, and the exclusion of known causes of granulomatous diseases. At time of presentation, none of them were receiving corticosteroids, nor had they within the previous 3

Clinical Characteristics

Seventy-nine patients with sarcoidosis (43 men and 36 women; mean age ± SD, 39 ± 12 years; 56 nonsmokers and 23 smokers), and 38 control subjects (19 men and 19 women; mean age, 37 ± 10 years; all nonsmokers) were studied.

One patient with sarcoidosis presented with radiographic stage 0, 28 patients presented with stage I, 36 patients presented with stage II, 12 patients presented with stage III, and 2 patients presented with stage IV disease. Serum CC16, KL-6, and SP-D values in patients with

Discussion

In this study, we compared the value of CC16, KL-6, and SP-D as serum markers in pulmonary sarcoidosis. Although all three pneumoproteins were significantly elevated in patients with sarcoidosis compared to control subjects, ROC curve analysis revealed best sensitivity for KL-6. The results on KL-6 are in agreement with a recent study of Ohnishi and colleagues,10 who demonstrated superiority of serum KL-6 over SP-D in detecting interstitial lung disease. However, their study did not include

ACKNOWLEDGMENT

The authors thank Xavier Dumont for laboratory assistance and Pieter Zanen for statistical advice.

References (20)

There are more references available in the full text version of this article.

Cited by (69)

  • Krebs von den Lungen-6 (KL-6), soluble programmed cell death-1 (sPD-1) and its ligand-1(sPDL-1) in systemic sclerosis patients: Relation to disease parameters

    2022, Egyptian Rheumatologist
    Citation Excerpt :

    KL-6 antigen is expressed mainly by alveolar type II pneumocytes and respiratory bronchiolar epithelial cells and may act as a specific biomarker for predicting and monitoring ILD course [6]. Elevated serum levels of KL-6 have been associated with several respiratory conditions such as idiopathic pulmonary fibrosis, hypersensitivity pneumonitis, SSc-ILD, myositis-associated ILD, sarcoidosis and advanced pulmonary tuberculosis [8,9]. Programmed cell death −1 (PD-1) protein, a member of the CD28 family of co-stimulatory molecules, delivers its pivotal inhibitory signals through interactions with its two major ligands, programmed death ligand-1 and −2 (PDL1 and 2).

  • Diagnostic and Prognostic Biomarkers for Chronic Fibrosing Interstitial Lung Diseases With a Progressive Phenotype

    2020, Chest
    Citation Excerpt :

    There is also evidence that specific HLA alleles, including HLA-DRB1∗1502, are associated with an increased risk of ILD in patients with RA.38,39 Elevations in levels of MMP-1 (serum), MMP-7 (serum, BALF, and induced sputum), and other MMPs are recognized in IPF (Table 2).13,43-78 In addition, serum and sputum from patients with IPF display significantly higher levels of IGFBP-2 (P < .001) compared with those from healthy subjects.46,47

  • Circulating lung biomarkers in idiopathic lung fibrosis and interstitial lung diseases associated with connective tissue diseases: Where do we stand?

    2020, Seminars in Arthritis and Rheumatism
    Citation Excerpt :

    In one study, SP-D distinguished IPF from other ILDs with sensitivity, specificity and accuracy of 70%, 65% and 68.5%, respectively [62]. However, in most studies, SP-D and SP-A were elevated in ILD (including lung cancers or infections) without specificity for one disease [68–71], suggesting that these biomarkers are rather general markers for alveolar damage than for specific diseases. Increased serum SP-A and SP-D were strong predictors of mortality in IPF in three independent studies [63–65], with better performance of a model combining both [65].

View all citing articles on Scopus

Dr. Janssen was supported by a grant from AstraZeneca.

View full text