title: YKL-40 and matrix metalloproteinases as potential biomarkers of inflammation and fibrosis in the development of bronchiolitis obliterans syndrome.
abstract: OBJECTIVE
  The development of bronchiolitis obliterans syndrome (BOS) after lung transplantation is characterized by inflammation, remodeling and fibrosis. Both YKL-40 and matrix metalloproteinase (MMP)-9 have shown to be involved in these processes. We measured serial YKL-40 and MMP-9 serum levels in lung transplant recipients and assessed their usefulness as biomarker for BOS. Furthermore, we investigate the relationship between these two potential biomarkers of BOS and MMP-7.
  
  
  METHODS
  Ten patients with BOS (BOS(pos)) and 10 matched patients without BOS (BOS(neg)) were included. Serial serum samples were collected after lung transplantation and prior to BOS. YKL-40, MMP-9 and MMP-7 serum levels were determined by ELISA.
  
  
  RESULTS
  The median concentrations of YKL-40 did not differ between BOS(pos) and BOS(neg) patients (p > 0.05). The median concentration of MMP-9 in BOS(pos) patients was significantly higher than in BOS(neg) patients (p < 0.0001). For MMP-9 as possible risk factor for BOS, a cut off value of 145 ng/ml has a sensitivity of 90% and a negative predictive value of 83%. Longitudinal analysis of YKL-40 and MMP-9 serum levels from the early post-transplant period onwards did not reveal a significant trend in time in both serum levels preceding BOS. In BOS(neg) patients MMP-9 showed an inverse relationship with MMP-7, that was absent in BOS(pos) patients.
  
  
  CONCLUSIONS
  From the moment of transplantation onwards, patients who eventually developed BOS had significantly increased MMP-9 serum levels in comparison with patients who did not develop BOS. Therefore, increased MMP-9 serum levels might be useful as risk factor for BOS.
authors.affiliation: Centre of Interstitial Lung Diseases, Department of Pulmonology, St Antonius Hospital, Nieuwegein, The Netherlands. l.kastelijn1@antoniusziekenhuis.nl
authors.forename: E A
authors.initials: EA
authors.lastname: Kastelijn
authors.forename: C H M
authors.initials: CH
authors.lastname: van Moorsel
authors.forename: H J T
authors.initials: HJ
authors.lastname: Ruven
authors.forename: N M
authors.initials: NM
authors.lastname: Korthagen
authors.forename: J M
authors.initials: JM
authors.lastname: Kwakkel-van Erp
authors.forename: E A
authors.initials: EA
authors.lastname: van de Graaf
authors.forename: P
authors.initials: P
authors.lastname: Zanen
authors.forename: D A
authors.initials: DA
authors.lastname: van Kessel
authors.forename: J C
authors.initials: JC
authors.lastname: Grutters
mesh_terms: D054392:Adipokines / Q000097:blood*; D000328:Adult; D015415:Biomarkers / Q000097:blood*; D001989:Bronchiolitis Obliterans / Q000097:blood* / Q000453:epidemiology; D000071451:Chitinase-3-Like Protein 1; D005260:Female; D006801:Humans; D037102:Lectins / Q000097:blood*; D008171:Lung Diseases / Q000097:blood; D016040:Lung Transplantation; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D012307:Risk Factors
chemical_list: D054392:Adipokines; D015415:Biomarkers; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D037102:Lectins; D020783:Matrix Metalloproteinase 7; D020780:Matrix Metalloproteinase 9