Serum latent transforming growth factor-β binding protein 4 as a novel biomarker for idiopathic pleuroparenchymal fibroelastosis

Respir Med. 2020 Sep:171:106077. doi: 10.1016/j.rmed.2020.106077. Epub 2020 Jul 3.

Abstract

Background: Idiopathic pleuroparenchymal fibroelastosis (IPPFE) is a rare idiopathic interstitial pneumonia characterized by an upper lobe-dominant interstitial increase in predominantly elastic fibers. The accumulation of cases has resulted in a refinement of the disease concept, but there are no blood biomarkers to aid in the diagnosis or prediction of a progressive phenotype among PPFE patients. Several organizers, including latent transforming growth factor-β binding protein 4 (LTBP-4), are known to be involved in elastogenesis. However, the potential of LTBP-4 as a blood biomarker for PPFE has not been investigated.

Methods: We selected cases of clinically or histologically diagnosed IPPFE (n = 20) along with idiopathic pulmonary fibrosis (IPF) patients (n = 39) and healthy controls (n = 10). We quantified the protein levels of LTBP-4 in lung tissues and serum samples.

Results: The LTBP-4 levels in lung tissue of PPFE patients were 2.16 times higher than those of IPF patients (p = 0.032). The serum concentration of LTBP-4 (pg/ml) in IPPFE was higher than that in healthy controls (1429 [154-3620] vs. 187 [56.4-490], p = 0.013). The serum concentration of LTBP-4 in IPPFE was markedly higher than that in IPF without a significant difference (1429 [154-3620] vs. 915 [491-1967], p = 0.671). In addition, a higher concentration of LTBP-4 was associated with a poor prognosis in IPPFE patients.

Conclusions: The serum concentration of LTBP-4 may aid in the diagnosis of IPPFE or the prediction of an aggressive phenotype.

Keywords: Elastic fibers; Elastogenesis; Elastosis; Idiopathic pulmonary fibrosis; Krebs von den Lungen-6.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Disease Progression
  • Elastic Tissue / pathology
  • Female
  • Humans
  • Idiopathic Interstitial Pneumonias / diagnosis*
  • Idiopathic Interstitial Pneumonias / pathology
  • Idiopathic Pulmonary Fibrosis / diagnosis*
  • Idiopathic Pulmonary Fibrosis / pathology
  • Latent TGF-beta Binding Proteins / blood*
  • Male
  • Middle Aged
  • Mucin-1 / blood
  • Phenotype
  • Predictive Value of Tests
  • Retrospective Studies
  • Tomography, X-Ray Computed

Substances

  • Biomarkers
  • LTBP4 protein, human
  • Latent TGF-beta Binding Proteins
  • MUC1 protein, human
  • Mucin-1