Table 2. Candidate biomarkers for idiopathic pulmonary fibrosis (IPF)
KL-6A high-molecular weight glycoprotein highly expressed in tissue sections from patients with ILDs [35]. Elevated levels of serum KL-6 have been found in patients with clinically confirmed progression [33] and have been associated with increased mortality risk [36, 37].
SP-A and SP-DC-type lectins produced mainly by alveolar epithelial type II cells. Serum levels of SP-A and SP-D are increased in IPF (but also other pulmonary diseases) [3843] and are strongly predictive of mortality [44].
CD28A co-stimulatory molecule normally expressed on most CD4+ T-cells. Down regulation of CD28 on peripheral CD4+ T-cells has been associated with increased risk of lung transplantation within 1 yr [45].
Circulating fibrocytesThought to be progenitors for fibroblasts participating in the pathogenesis of lung fibrosis [46, 47]. Circulating fibrocytes were increased in IPF, with significant further increases during acute exacerbations. A proportion of >5% of peripheral blood leukocytes was associated with increased mortality in these patients [48].
Angiogenic factorsThought to play a role in the pathogenesis of IIPs. Elevated levels of the potent angiogenic factors VEGF and IL-8 have been associated with IPF and progressive disease [49, 50].
MMPsMatrix degrading enzymes thought to be critically involved in the pathology of pulmonary fibrosis [5153]. Plasma MMP1 and MMP7 levels are significantly elevated in IPF patients [54]. MMP7 levels are consistently elevated in asymptomatic versus symptomatic IPF, indicating that it may be a marker for early disease [55].
Oxidative stressMay be implicated in the epithelial dysfunction underlying pulmonary fibrosis [56]. Oxidant burden has been shown to be elevated in the serum [57] of IPF patients.
  • KL-6: Krebs von Lungen factor-6; SP: surfactant protein; MMP; matrix metalloproteinase; ILD: interstitial lung disease; IIP: idiopathic interstitial pneumonia; VEGF: vascular endothelial growth factor; IL: interleukin.