Elevated serum Krebs von den Lungen-6 in systemic sclerosis: a marker of lung fibrosis and severity of the disease

Rheumatol Int. 2018 May;38(5):813-819. doi: 10.1007/s00296-018-3987-3. Epub 2018 Feb 17.

Abstract

Objectives: We aimed to assess the clinical significance of Krebs von den Lungen-6 (KL-6) in the diagnosis and severity of interstitial lung disease (ILD) in a French cohort of patients with systemic sclerosis (SSc).

Methods: Serum KL-6 concentrations were measured with chemiluminescent enzyme immunoassay (CLEIA) in 75 SSc patients. Patients were divided into two groups according to the presence of interstitial lung disease (SSc-ILD versus SSc-without ILD) on chest High-Resolution Computed Tomography. Pulmonary function tests, main manifestations and severity of the lung disease (Medsger's severity scale) were collected.

Results: KL-6 serum concentrations were significantly higher in SSc-ILD patients than in those without ILD (p < 10-4) and were inversely correlated with forced vital capacity, total lung capacity and diffuse lung capacity of carbon monoxide. Serum KL-6 level superior to 872 U/ml appeared as the optimal cut-off value associated with ILD. Patients with a restrictive pulmonary syndrome and dyspnoea had significant higher KL-6 serum concentrations. SSc patients with anti-topoisomerase 1 antibodies had higher KL-6 serum levels than patients with anti-centromere antibodies (p < 10- 4). ILD and anti-topoisomerase 1 antibodies were independent factors associated with KL-6 in multivariate analysis. Interestingly, KL-6 serum concentrations positively increased with the patient lung severity.

Conclusions: Our study confirms that KL-6 is an accurate biomarker for the diagnosis of SSc-ILD in a French cohort of patients. High KL-6 levels should prompt physicians to assess ILD with pulmonary imaging and pulmonary functions tests. Prospective clinical studies are still required to determine whether levels of KL-6 might predict progression of ILD as well as its usefulness in the timing of therapeutic intervention.

Keywords: Anti-topoisomerase 1 antibody (Scl70); Disease severity; Krebs von den Lungen-6; Lung fibrosis; Systemic sclerosis.

MeSH terms

  • Aged
  • Antibodies, Antinuclear / blood
  • Biomarkers / blood
  • Centromere / immunology
  • DNA Topoisomerases, Type I / immunology
  • Female
  • France
  • Humans
  • Logistic Models
  • Lung Diseases, Interstitial / blood*
  • Lung Diseases, Interstitial / diagnosis
  • Lung Diseases, Interstitial / etiology
  • Lung Diseases, Interstitial / physiopathology
  • Lung* / diagnostic imaging
  • Lung* / pathology
  • Lung* / physiopathology
  • Male
  • Middle Aged
  • Mucin-1 / blood*
  • Multivariate Analysis
  • Odds Ratio
  • Predictive Value of Tests
  • Pulmonary Diffusing Capacity
  • Pulmonary Fibrosis / blood*
  • Pulmonary Fibrosis / diagnosis
  • Pulmonary Fibrosis / etiology
  • Pulmonary Fibrosis / physiopathology
  • Risk Factors
  • Scleroderma, Systemic / blood*
  • Scleroderma, Systemic / complications
  • Scleroderma, Systemic / diagnosis
  • Severity of Illness Index
  • Tomography, X-Ray Computed
  • Total Lung Capacity
  • Up-Regulation
  • Vital Capacity

Substances

  • Antibodies, Antinuclear
  • Biomarkers
  • MUC1 protein, human
  • Mucin-1
  • DNA Topoisomerases, Type I
  • TOP1 protein, human