5 years ago

Circulating fibroblast activation protein activity and antigen levels correlate strongly when measured in liver disease and coronary heart disease

Bharvi Maneck, Mark D. Gorrell, H. Emma Zhang, David G. Bowen, Geoffrey W. McCaughan, Fiona M. Keane, Dingeman C. Rijken, Shirley Uitte de Willige, Joyce J. M. C. Malfliet, Frank W. G. Leebeek

by Shirley Uitte de Willige, Fiona M. Keane, David G. Bowen, Joyce J. M. C. Malfliet, H. Emma Zhang, Bharvi Maneck, Geoffrey W. McCaughan, Frank W. G. Leebeek, Dingeman C. Rijken, Mark D. Gorrell

Background and aim

Circulating fibroblast activation protein (cFAP) is a constitutively active enzyme expressed by activated fibroblasts that has both dipeptidyl peptidase and endopeptidase activities. We aimed to assess the correlation between cFAP activity and antigen levels and to compare variations in levels.


In plasma of 465 control individuals, 368 patients with coronary heart disease (CHD) and 102 hepatitis C virus (HCV) infected patients with severe liver disease before and after liver transplant, cFAP activity levels were measured with a newly developed cFAP activity assay. In the same samples, cFAP antigen levels were measured using a commercially available cFAP ELISA. Correlation analyses between activity and antigen levels were performed by calculating Pearson’s correlation coefficient (ρ). Additionally, normal ranges, determinants and differences between cohorts and between anticoagulants were investigated.


cFAP activity and antigen levels significantly correlated in controls (ρ: 0.660, p<0.001) and in CHD patients (ρ: 0.709, p<0.001). cFAP activity and antigen levels in the HCV cohort were significantly lower in the samples taken after liver transplantation (p<0.001) and normalized toward levels of healthy individuals. Furthermore, cFAP activity and antigen levels were higher in men and significantly associated with body mass index. Also, cFAP activity and antigen levels were higher in EDTA plasma as compared to the levels in citrated plasma from the same healthy individuals.


For analyzing cFAP levels, either activity levels or antigen levels can be measured to investigate differences between individuals. However, it is of importance that blood samples are collected in the same anticoagulant.

Publisher URL: http://journals.plos.org/plosone/article

DOI: 10.1371/journal.pone.0178987

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