The role of the lectin pathway of complement in the pathogenesis of interstitial lung diseases (ILDs) is largely unknown. Pattern recognition receptors (PRR) of the lectin pathway are involved in the clearance of apoptotic cells either via activation of the complement system or as direct opsonins. As recent findings suggest a role of apoptosis in the development of pulmonary fibrosis, the influence of plasma lectins has lately been considered in various ILDs, but data on local concentrations in the lungs are lacking. This study investigated the role of mannose-binding lectin (MBL), ficolin-2 and ficolin-3 in ILD patients with a focus on idiopathic pulmonary fibrosis (IPF) and sarcoidosis.
A case control study was conducted involving 80 patients with different forms of ILD as well as 40 control patients undergoing routine flexible bronchoscopy with bronchoalveolar lavage (BAL). Plasma and BAL fluid (BALF) levels of MBL, ficolin-2 and ficolin-3 as well as complement split products C4d and C5a (only in BALF) were measured by enzyme-linked immunosorbent assays. Eight single-nucleotide polymorphisms (SNPs) of MBL and ficolin-2 were determined by genotyping and tested for their association with ILDs.
We included 35, 35, 10, and 40 patients with sarcoidosis, idiopathic pulmonary fibrosis (IPF), other ILD, and a control group, respectively. BALF but not plasma levels of the three PRR were significantly elevated in sarcoidosis patients compared to a control group without ILD (MBL: median 66.8 vs. 24.6 ng/ml,
This is the first study to simultaneously assess systemic and local lectin pathway protein levels in ILD patients. Our data suggest an involvement of PRR of the lectin pathway in the pathogenesis of sarcoidosis given the significantly higher BALF levels compared to a control group. Additional analyses in a larger patient cohort are required to confirm or refute a potential effect of local and/or systemic ficolin-2 levels in IPF patients.