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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
First Department of Medicine, Hokkaido University School of Medicine, and Division of Laboratory and Transfusion Medicine, Hokkaido University Hospital, Sapporo, Japan.
Masahiko
M
Shigemura
Yasuyuki
Y
Nasuhara
Satoshi
S
Konno
Chikara
C
Shimizu
Kazuhiko
K
Matsuno
Etsuro
E
Yamguchi
Masaharu
M
Nishimura
D000293:Adolescent; D000328:Adult; D000368:Aged; D000906:Antibodies; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D000939:Epitopes / Q000276:immunology; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D018396:Mucin-1 / Q000097:blood* / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012507:Sarcoidosis / Q000097:blood*; D012907:Smoking / Q000235:genetics; D055815:Young Adult
D000906:Antibodies; D000939:Epitopes; C060192:MUC1 protein, human; D018396:Mucin-1