title: Serum KL-6 and surfactant protein-D as monitoring and predictive markers of interstitial lung disease in patients with systemic sclerosis and mixed connective tissue disease.
abstract: BACKGROUND
  Interstitial lung disease (ILD) is frequent complication of systemic sclerosis (SSc) and mixed connective tissue disease (MCTD). The disease is heterogeneous, and its outcome is unpredictable. Some patients have severe and progressive deterioration of ILD, which is the leading cause of mortality. We aimed to determine whether serum levels of Krebs von den Lungen-6 (KL-6) and surfactant protein-D (SP-D) correlate with SSc/MCTD-associated ILD activity.
  
  
  METHODS
  We retrospectively analyzed the medical records of 40 patients with SSc/MCTD-associated ILD: 29 patients with SSc and 11 patients with MCTD. Measurement of serum KL-6 and SP-D levels, pulmonary function tests, and high-resolution computed tomography (HRCT) performed in parallel were reviewed.
  
  
  RESULTS
  Serum KL-6 correlated positively with diffusing capacity of the lung for carbon monoxide (DLCO) (% predicted) and disease extent on HRCT, and the changes in serum levels of KL-6 were significantly related to the changes in forced vital capacity (FVC) in SSc/MCTD-associated ILD. On the other hand, multivariate logistic regression analyses with calculation of the area under the curve of the receiver-operating characteristic curve suggested that a higher serum level of SP-D was a significant predictor of FVC decline in SSc/MCTD-associated ILD.
  
  
  CONCLUSIONS
  Our study suggests that serum KL-6 can be a useful monitoring tool of SSc/MCTD-associated ILD activity. In contrast, serum SP-D may be a significant predictor of potential FVC decline in the short term.
authors.affiliation: Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan;; Department of Respiratory Medicine, Tokyo Jikei University Hospital, Tokyo, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Yamakawa
authors.affiliation: Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Hagiwara
authors.affiliation: Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan;; Department of Respiratory Medicine, Tokyo Jikei University Hospital, Tokyo, Japan.
authors.forename: Hideya
authors.initials: H
authors.lastname: Kitamura
authors.affiliation: Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan;; Department of Respiratory Medicine, Tokyo Jikei University Hospital, Tokyo, Japan.
authors.forename: Yumie
authors.initials: Y
authors.lastname: Yamanaka
authors.affiliation: Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ikeda
authors.affiliation: Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan.
authors.forename: Akimasa
authors.initials: A
authors.lastname: Sekine
authors.affiliation: Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan.
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Baba
authors.affiliation: Department of Pathobiology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Okudela
authors.affiliation: Department of Radiology, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan.
authors.forename: Tae
authors.initials: T
authors.lastname: Iwasawa
authors.affiliation: Department of Pathology, Japanese Red Cross Medical Center, Tokyo, Japan.
authors.forename: Tamiko
authors.initials: T
authors.lastname: Takemura
authors.affiliation: Department of Respiratory Medicine, Tokyo Jikei University Hospital, Tokyo, Japan.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Kuwano
authors.affiliation: Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ogura
keywords: Systemic sclerosis (SSc); biomarker; interstitial lung disease (ILD); mixed connective tissue disease (MCTD)