Serum Complement C3f and Fibrinopeptide A Are Potential Novel Diagnostic Biomarkers for Non-Alcoholic Fatty Liver Disease: A Study in Qingdao Twins

Abstract

AimsTo compare the different serum peptidome patterns between twins with and without non-alcoholic fatty liver disease (NAFLD) in order to help understand the pathogenesis of NAFLD and to identify potential diagnostic and therapeutic targets.MethodsThe peptidomics patterns of 63 cases with NAFLD were compared with their twin healthy controls in Qingdao, China. Peptides between 800Da and 3500Da were captured and concentrated using C18 reversed-phase columns, followed by MALDI-TOF mass spectrometry. The sequences of peptides associated with NAFLD were further identified by MALDI-TOF-TOF. Further validation studies were conducted. One hundred additional serum samples were detected by commercially available ELISA kits to calculate the concentrations of complement C3f and fibrinopeptide A, respectively. The differences of these two peptides in the NAFLD and control groups were compared using SPSS 17.0, respectively.ResultsCompared with healthy controls, eleven peaks (861.1, 877.07, 904.5, 1206.57, 1350.64, 1518.7, 1690.9, 1777.94, 2931.29, 3190.4, 3261.4) were up-regulated and 7 peaks (942.44, 1020.47, 1060.06, 1211.7, 1263.63, 1449.76, 2768.3) were down-regulated in the NAFLD group. Two peptides derived from complement C3f and fibrinopeptide A, respectively, had the highest ROC values indistinguishing NAFLD cases from their normal controls. In the validation group, the concentrations of complement C3f and fibrinopeptide A (1466.929±78.306 pg/ml, 4.189±0.326 ng/ml, respevtively) in NAFLD group was higher than in control group (complement C3f 1159.357±99.624 pg/ml, FPA 3.039±0.483 ng/ml; P<0.05).ConclusionsIn this study, we established apeptidomics pattern that could help distinguish NAFLD patients from their twin controls. The differently-regulated peptides identified in our study may be potential diagnostic markers or therapeutic targets for NAFLD.

Complement C3 and fatty liver disease in Rheumatoid arthritis patients: a cross-sectional study

“…Systemic activation of complement through the alternative pathway has been demonstrated in liver biopsies of NAFLD patients [22,23] and associated with an increase in circulating levels of its cleavage product C3a [38]. Similarly, a peptidomic study involving patients with NAFLD and twin controls demonstrated significantly higher levels of C3f [39]. Moreover, two large clinical studies confirmed the association between C3 levels and NAFLD [24,25] independently of other metabolic features.…”

“…However, the relationship between NAFLD and obesity is already well-established in the literature [9]. Similarly, a peptidomic study involving patients with NAFLD and twin controls demonstrated significantly higher levels of C3f [39]. Complement proteins are synthesized mainly in the liver but visceral adipose tissue contributes significantly to C3 levels during obesity and other dysmetabolic or inflammatory states.…”

Proteomic screening of plasma identifies potential noninvasive biomarkers associated with significant/advanced fibrosis in patients with nonalcoholic fatty liver disease

“…The role of complement in liver diseases is less well characterized. The complement components C3 and C5 were reported to be associated with NAFLD [39][40][41] and C5 had a causal role in liver fibrogenesis [42]. There are strong and persistent stimuli for complement activation in NAFLD through multiple pathways, including the classical pathway and the lectin pathway [43], as well as the alternative pathway [44].…”

Fibrinopeptide A induces C‐reactive protein expression through the ROS‐ERK1/2/p38‐NF‐κB signal pathway in the human umbilical vascular endothelial cells

“…Atherosclerosis is the main pathological basis of the ischemic cardiocerebrovascular diseases. Although the pathogenesis of atherosclerosis is not well defined, more and more evidence from the find that the high level of FPA in blood means activation of the coagulation system (Ekwere, Ebele, Ekanem, & Ogunro, 2014;Omarov, Sultanov, & Ragimov, 2012) and occurs in the patients with venous thrombosis, pulmonary embolism, and ischemic heart disease as a biomarker (Gianazza et al, 2010;Morris et al, 2003;Xin et al, 2014). However, to date, little is known about the pathological effects of FPA in the cardiovascular system.…”