HNP and CCSP protein levels are differentially regulated in BAL from patients with obstructive and restrictive chronic allograft dysfunctions

Abstract

After Lung Transplantation (LTx), Chronic Lung Allograft Dysfunction (CLAD) limits the median survival time to 5 years. Recently, besides the well known bronchiolitis obliterans syndrome (BOS), a more aggressive restrictive form (rCLAD), displaying parenchymal fibrosis, has been described. We propose here to analyze the levels of Human Neutrophil Peptides (HNP) and Clara Cell Secreted Protein (CCSP), both known to be dysregulated in BOS, in BAL from stable, BOS and rCLAD patients. The BAL of 49 patients was analyzed (stable : n = 20; BOS : n = 22; rCLAD : n = 7). BOS was defined as FEV 1 1 to (1) that HNP levels were significantly increased in BOS, but not in rCLAD patients compared to stable controls ([HNP] : stable patients : 8,76.10 4 ± 3,39.10 4 pg.mL -1 ; BOS : 2,13.10 5 ± 4,65.10 4 pg.mL -1 , * p =0.005; rCLAD : 1,45.10 5 ± 4,77.10 4 pg.mL -1 , p =0,08), (2) that CCSP levels were significantly decreased in BOS, but not in rCLAD patients compared to stable controls ([CCSP] : stable patients : 1352 ± 262 ng. mL -1 ; BOS : 391 ± 119 ng. mL -1 ; rCLAD : 687 ± 321 ng. mL -1 ). Our data provide evidence that two well-accepted markers of BOS are specific for the obliterative but not the restrictive form of the disease. This finding underlines the possibility to distinguish between both types of disease, and claims for large scale proteomic analysis of BOS and rCLAD in order to identify new diagnostic tools.