Effects of molecular structural variants on serum Krebs von den Lungen-6 levels in sarcoidosis

Western blot analysis using anti-KL-6 antibody was performed simultaneously on the bronchoalveolar lavage fluid (BALF) and serum obtained from 128 subjects with sarcoidosis.KL-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.The 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.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). In normal lung tissue, KL-6 is expressed on type II pneumocytes [1,5]. KL-6 is present in high concentrations in bronchoalveolar lavage fluid (BALF) and also circulates in blood [6]. Serum KL-6 is specifically elevated in a majority of patients with interstitial lung diseases (ILDs), and this phenomenon is considered to reflect the production by regenerating type II epithelial cells based on disease activity [6-13]. Therefore, measurement of serum KL-6 is widely accepted, particula