Heterogeneity of chronic lung allograft dysfunction: Insights from protein expression in broncho alveolar lavage

JOURNAL OF HEART AND LUNG TRANSPLANTATION

卷:30

Article

Verleden, Stijn E.^1,2  Vos, Robin^1,2  Mertens, Veerle^1,3  Willems-Widyastuti, Anna^1,2  De Vleeschauwer, Stephanie I.^1,2  Dupont, Lieven J.^1,2  Verleden, Geert M.^1,2  Van Raemdonck, Dirk E.¹  Vanaudenaerde, Bart M.^1,2 

[1] Katholieke Univ Leuven, Lung Transplantat Unit, B-3000 Louvain, Belgium

[2] Katholieke Univ Leuven, Lab Pneumol, B-3000 Louvain, Belgium

[3] Katholieke Univ Leuven, Ctr Gastroenterol Res, B-3000 Louvain, Belgium

关键词: bronchiolitis obliterans syndrome;    chronic lung allograft dysfunction;    lung transplantation;    neutrophilic reversible allograft dysfunction;    bronchoalveolar lavage;    lung rejection;   

DOI  :  10.1016/j.healun.2010.12.008

来源: Elsevier

【 摘 要 】

BACKGROUND: Chronic lung allograft dysfunction (CLAD) remains a major risk factor for death after lung transplantation. Previous data suggested that within CLAD at least 2 phenotypes are present: a neutrophilic type (nCLAD or neutrophilic reversible allograft dysfunction [NRAD]), reversible with azithromycin therapy, vs a low neutrophilic type, non-responsive to azithromycin (fibrotic bronchiolitis obliterans syndrome [fBOS]). We aimed to further characterize this dichotomy by measuring multiple proteins in the bronchoalveolar lavage (BAL) fluid of 28 lung recipients. METHODS: Patients were retrospectively subdivided by the absence or presence of CLAD and subsequently by their response to azithromycin, resulting in 3 groups: 10 stable, 9 responsive (nCLAD/NRAD), and 9 non-responsive (fBOS). Enzyme-linked immunosorbent assay was used to measure 32 different proteins. RESULTS: Protein variations were predominantly present in the nCLAD/NRAD group, whereas no differences were observed in the fBOS group compared with control. MCP-1 (p < 0.01), RANTES (p < 0.05), IL-beta (p < 0.01), IL-8 (p < 0.01), TIMP-1 (p < 0.01), MMP-8 (p < 0.01), MMP-9 (p < 0.01), HGF (p < 0.001), MPO (p < 0.01), and bile acid (p < 0.05) concentrations were upregulated in nCLAD/NRAD compared with fBOS, whereas PDGF-AA (p < 0.05) was downregulated. CONCLUSIONS: These data provide further evidence that within CLAD there is a heterogeneity of phenotypes with different mechanisms involved. Further investigation is warranted to unravel the pathophysiology of both phenotypes. J Heart Lung Transplant 2011;30:667-73 (C) 2011 International Society for Heart and Lung Transplantation. All rights reserved.

【 授权许可】

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