Collagen neoepitope biomarkers are increased in allergic broncho-pulmonary aspergillosis in Cystic Fibrosis

Background Cystic fibrosis (CF) is a fibrotic disease, with pertinence of structural alterations to the lung extracellular matrix (ECM) to the overall well-being of people with CF (pwCF). Allergic broncho-pulmonary aspergillosis (ABPA) is a severe allergic, co-morbidity of CF, difficult to differentiate early from other CF symptoms. Characteristically, high serum levels of a type IV collagen (COL4) neoepitope biomarker (NEM: C4Ma3) are found in severe, exacerbating type 2 asthma. It is not understood if lung remodelling in CF w/wo ABPA is associated with higher C4Ma3 or other ECM fragments. This pilot study tests the hypothesis that the additional allergic inflammation in ABPA increases collagen degradation in the lung.

Methods In a pilot study, NEM from type III (C3M) and IV (C4Ma3, C4M) collagen, elastin (EL-NE) and CRP (CRPM) were quantified in serum from 36 pwCF aged 4.6 to 36.4 years (median 13.1 y) and correlated with clinical parameters. ABPA was confirmed in n=9. Healthy controls form the All-Age-Asthma cohort served as age and gender matched controls. Confounders: Age, gender and sample age.

Results Collagen, elastin or CRP neoepitope markers did not correlate individually with lung function or pseudomonas colonisation. PwCF with ABPA showed significantly elevated levels for C4Ma3 (4.02 vs. 2.77 ng/ml, p<0.01), as well as C4M (31.16 vs. 20.19 ng/mL, p<0.01) and C3M (10.38 vs. 6.76 ng/ml, p<0.01). Serum levels of pwCF w/o ABPA were not significantly different to age matched healthy controls.

Discussion In pwCF and ABPA NEM indicate elevated degradation of collagens. NEM may afford a novel strategy to identify active ABPA vs. a severe form of CF. Larger studies are warranted to confirm these findings.

Publikationsverlauf

Artikel online veröffentlicht:
21. September 2022