Abstract
About 50% of lung transplanted patients develop chronic lung allograft dysfunction (CLAD) within 5 years after transplantation, leading to decreased lung function. Bronchiolitis obliterans syndrome (BOS), a type of CLAD, is characterized by fibrotic lesions in small airways. Risk factors, such as acute rejection, are recognized, but little is known about the initiation of the fibrosis. We hypothesize that changes in the distribution of extracellular matrix proteins might be a marker for the disease process.
Our study aimed to map total collagen, collagen type IV and biglycan in transbronchial biopsies taken at 3 and 12 months after transplantation using Masson's Trichrome staining and immunohistochemistry. Staining patterns were quantified and related to the BOS status of the patients (n=60) and clinical data in a 5-years follow-up.
In the alveolar compartment, total collagen was found increased in patients developing BOS (3 vs. 12 months, p=0.02). Collagen type IV was found increased in patients without BOS (3 vs. 12 months, p=0.01) and biglycan seemed stable. In contrast, BOS patients showed increased submucosal biglycan in the small airways (3 vs. 12 months, p=0.02), while total collagen and collagen type IV were stable.
BOS patients who had treated acute rejection episodes within the first 3 months after transplantation showed decreased total collagen (no vs. ≥1 episode, p=0.004) in the alveoli and decreased biglycan in the small airway submucosa (no vs. ≥1 episode, p=0.03) at 3 months.
The results may indicate that the various lung compartments may have a different susceptibility to disease-causing insults resulting in changes in complex remodeling processes that eventually may lead to BOS.
- Copyright ©the authors 2016
