Comprehensive investigation of novel serum markers of pulmonary fibrosis associated with systemic sclerosis and dermato/polymyositis

Clin Exp Rheumatol. 2008 May-Jun;26(3):414-20.

Abstract

Objective: To investigate the association between serum levels and clinical signs of lung fibrosis in patients with systemic sclerosis and inflammatory myopathies.

Methods: ELISA tests for a mucin-like glycoprotein KL-6, von Willebrandt factor (vWF), soluble E-selectin (sES) and surfactant protein D (SP-D) were performed in sera of 104 patients with systemic sclerosis, 31 patients with poly/dermatomyositis) and 24 patients with Raynaud's phenomenon as controls. The clinical and laboratory data were evaluated by a simple standard protocol including chest x-ray, lung function tests, echocardiography and, in selected cases, high resolution computer tomography (HRCT). Clinically significant pulmonary fibrosis (PF) defined as a simultaneous presence of radiological sign of pulmonary fibrosis and restrictive impairment. Severe PF was established if HRCT scans showed diffuse interstitial lung disease with low diffusing capacity. End stage PF was determined as severe PF with very low diffusing capacity.

Results: Patients with pulmonary fibrosis on chest x-ray showed significantly elevated serum levels of KL-6, SP-D and vWF. Inverse correlation was found between serum levels of KL-6/SP-D and lung function parameters, such as DLCO% and FVC. With regard to HRCT findings, patients with elevated serum level of KL-6 showed significantly more frequently ground glass opacity, diffuse and honeycombing fibrosis than patients with normal level of KL-6. The sensitivity of KL-6 for PF in SSc is increased with the severity of PF (PF on chest x-ray < severe PF < end stage of PF). Lung fibrosis occurred more frequently in patients with simultaneously elevated KL-6 and sES compared to cases with a single positivity of either KL-6 or sES.

Conclusion: KL-6, SP-D, vWF and ES are good surrogate factors of pulmonary fibrosis but can not replace conventional diagnostic procedures. However, these markers are suitable for the assessment of progression and severity of pulmonary fibrosis in systemic autoimmune disorders once the diagnosis is established.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood
  • Case-Control Studies
  • Dermatomyositis / blood*
  • Dermatomyositis / complications
  • Disease Progression
  • E-Selectin / blood*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mucin-1 / blood*
  • Pulmonary Fibrosis / blood*
  • Pulmonary Fibrosis / complications
  • Pulmonary Fibrosis / diagnosis
  • Pulmonary Surfactant-Associated Protein D / blood*
  • Radiography, Thoracic
  • Raynaud Disease / blood
  • Respiratory Function Tests
  • Scleroderma, Systemic / blood*
  • Scleroderma, Systemic / complications
  • Sensitivity and Specificity
  • Severity of Illness Index
  • von Willebrand Factor / metabolism*

Substances

  • Biomarkers
  • E-Selectin
  • MUC1 protein, human
  • Mucin-1
  • Pulmonary Surfactant-Associated Protein D
  • von Willebrand Factor