Abstract
BackgroundSerum Krebs von den Lungen-6 (KL-6), which is classified as human mucin-1 (MUC1), is used as a marker of sarcoidosis and other interstitial lung diseases. However, there remain some limitations due to a lack of information on the factors contributing to increased levels of serum KL-6. This study was designed to investigate the factors contributing to increased levels of serum KL-6 by molecular analysis.MethodsWestern blot analysis using anti-KL-6 antibody was performed simultaneously on the bronchoalveolar lavage fluid (BALF) and serum obtained from 128 subjects with sarcoidosis.ResultsKL-6/MUC1 in BALF showed three bands and five band patterns. These band patterns were associated with the MUC1 genotype and the KL-6 levels. KL-6/MUC1 band patterns in serum were dependent on molecular size class in BALF. Significantly increased levels of serum KL-6, serum/BALF KL-6 ratio and serum soluble interleukin 2 receptor were observed in the subjects with influx of high molecular size KL-6/MUC1 from the alveoli to blood circulation. The multivariate linear regression analysis involving potentially relevant variables such as age, gender, smoking status, lung parenchymal involvement based on radiographical stage and molecular size of KL-6/MUC1 in serum showed that the molecular size of KL-6/MUC1 in serum was significant independent determinant of serum KL-6 levels.ConclusionsThe molecular structural variants of KL-6/MUC1 and its leakage behavior affect serum levels of KL-6 in sarcoidosis. This information may assist in the interpretation of serum KL-6 levels in sarcoidosis.
Highlights
Serum Krebs von den Lungen-6 (KL-6), which is classified as human mucin-1 (MUC1), is used as a marker of sarcoidosis and other interstitial lung diseases
In univariate analyses between serum KL-6 levels and potentially relevant variables, there were significant differences between the subjects without and with lung parenchymal involvement based on radiographical stage [14] (p = 0.020) and those with low and higher molecular size KL-6/MUC1 in serum (p < 0.001) (Table 5)
MUC1 band patterns in serum were dependent on molecular size class in bronchoalveolar lavage fluid (BALF), as proteins of different size classes did not pass through the alveolar-blood interface in a similar manner
Summary
Serum Krebs von den Lungen-6 (KL-6), which is classified as human mucin-1 (MUC1), is used as a marker of sarcoidosis and other interstitial lung diseases. There remain some limitations due to a lack of information on the factors contributing to increased levels of serum KL-6. This study was designed to investigate the factors contributing to increased levels of serum KL-6 by molecular analysis. Krebs von den Lungen-6 (KL-6) is a mucinous sialylated sugar chain on human mucin-1 (MUC1) [1,2]. MUC1 consists of a large extracellular domain, a single-pass transmembrane region, and an intracellular cytoplasmic tail [3,4]. The large extracellular domain contains a variable number of tandem repeat (VNTR) regions that are heavily glycosylated (Figure 1).
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