Serum KL-6 is a predictor of outcome in pulmonary alveolar proteinosis

Orphanet J Rare Dis. 2013 Apr 4;8:53. doi: 10.1186/1750-1172-8-53.


Background: Pulmonary alveolar proteinosis (PAP) is a rare disorder characterised by abundant alveolar accumulation of surfactant lipoproteins. Serum levels of KL-6, high molecular weight human MUC1 mucin, are increased in the majority of patients with PAP. The prognostic significance of KL-6 in PAP is still unknown. Aim of the study was to evaluate whether serum KL-6 levels correlate with the outcome of the disease.

Patients and methods: From 2006 to 2012, we prospectively studied 33 patients with primary autoimmune PAP. We measured serum KL-6 levels by ELISA (Eisai, Tokyo, Japan), and evaluated the correlation between initial KL-6 levels and clinical variables. Disease progression was defined as deterioration of symptoms, and/or lung function, and/or chest imaging.

Main results: The initial serum KL-6 levels were significantly correlated with the baseline PaO2, A-aDO2, DLCO, VC and TLC (p=0.042, 0.012, 0.012, 0.02 and 0.013, respectively). The change over time of serum KL-6 correlated with the change over time of DLCO (p=0.017). The initial serum KL-6 levels were significantly higher in patients with disease progression than in those with remission (p<0.001). At a cut-off level of 1526 U/mL, the initial serum KL-6 level predicted disease progression (Se 81%, Sp 94%). At a cut-off level of 2157 U/mL, the initial serum KL-6 predicted the necessity of repeated whole lung lavage (Se 83%, Sp 96%). In the multivariate analysis, the initial serum level of KL-6 was the strongest predictor of disease progression (HR 9.41, p=0.008).

Conclusions: Serum KL-6 seems to predict outcome in PAP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Disease Progression
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mucin-1 / blood*
  • Prognosis
  • Proportional Hazards Models
  • Prospective Studies
  • Pulmonary Alveolar Proteinosis / blood*
  • Pulmonary Alveolar Proteinosis / physiopathology
  • Respiratory Function Tests
  • Treatment Outcome
  • Young Adult


  • Biomarkers
  • MUC1 protein, human
  • Mucin-1