Frontiers in Immunology (May 2021)

Connective Tissue Growth Factor Is Overexpressed in Explant Lung Tissue and Broncho-Alveolar Lavage in Transplant-Related Pulmonary Fibrosis

  • Arno Vanstapel,
  • Arno Vanstapel,
  • Roel Goldschmeding,
  • Roel Broekhuizen,
  • Tri Nguyen,
  • Annelore Sacreas,
  • Janne Kaes,
  • Tobias Heigl,
  • Stijn E. Verleden,
  • Alexandra De Zutter,
  • Geert Verleden,
  • Geert Verleden,
  • Birgit Weynand,
  • Birgit Weynand,
  • Erik Verbeken,
  • Erik Verbeken,
  • Laurens J. Ceulemans,
  • Laurens J. Ceulemans,
  • Dirk E. Van Raemdonck,
  • Dirk E. Van Raemdonck,
  • Arne P. Neyrinck,
  • Arne P. Neyrinck,
  • Helene M. Schoemans,
  • Bart M. Vanaudenaerde,
  • Robin Vos,
  • Robin Vos

DOI
https://doi.org/10.3389/fimmu.2021.661761
Journal volume & issue
Vol. 12

Abstract

Read online

BackgroundConnective tissue growth factor (CTGF) is an important mediator in several fibrotic diseases, including lung fibrosis. We investigated CTGF-expression in chronic lung allograft dysfunction (CLAD) and pulmonary graft-versus-host disease (GVHD).Materials and MethodsCTGF expression was assessed by quantitative real-time polymerase chain reaction (qPCR) and immunohistochemistry in end-stage CLAD explant lung tissue (bronchiolitis obliterans syndrome (BOS), n=20; restrictive allograft syndrome (RAS), n=20), pulmonary GHVD (n=9). Unused donor lungs served as control group (n=20). Next, 60 matched lung transplant recipients (BOS, n=20; RAS, n=20; stable lung transplant recipients, n=20) were included for analysis of CTGF protein levels in plasma and broncho-alveolar lavage (BAL) fluid at 3 months post-transplant, 1 year post-transplant, at CLAD diagnosis or 2 years post-transplant in stable patients.ResultsqPCR revealed an overall significant difference in the relative content of CTGF mRNA in BOS, RAS and pulmonary GVHD vs. controls (p=0.014). Immunohistochemistry showed a significant higher percentage and intensity of CTGF-positive respiratory epithelial cells in BOS, RAS and pulmonary GVHD patients vs. controls (p<0.0001). BAL CTGF protein levels were significantly higher at 3 months post-transplant in future RAS vs. stable or BOS (p=0.028). At CLAD diagnosis, BAL protein content was significantly increased in RAS patients vs. stable (p=0.0007) and BOS patients (p=0.042). CTGF plasma values were similar in BOS, RAS, and stable patients (p=0.74).ConclusionsLung CTGF-expression is increased in end-stage CLAD and pulmonary GVHD; and higher CTGF-levels are present in BAL of RAS patients at CLAD diagnosis. Our results suggest a potential role for CTGF in CLAD, especially RAS, and pulmonary GVHD.

Keywords