title: Lectin-complement pathway molecules are decreased in patients with cirrhosis and constitute the risk of bacterial infections.
abstract: Lectin pathway molecules of the complement system are synthesized by hepatocytes and have pivotal role in innate host defence against infectious organisms. Ficolins (FCNs) act as soluble pattern recognition molecules, while mannan-binding lectin serine proteases(MASPs) do as effector molecules in elimination of pathogens. We aimed to study the significance of low level of these molecules in the development of cirrhosis-associated bacterial infections, which has not been elucidated so far.
  
  
  
  Sera of 266 stable outpatients with cirrhosis and 160 healthy subjects were assayed for a panel of lectin molecules (FCN-2, FCN-3 and MASP-2) by ELISA. In cirrhosis, a 5-year follow-up observational study was conducted to assess a possible association between lectin levels and development of clinically significant bacterial infections(CSI).
  
  
  
  FCN-2, FCN-3 and MASP-2 levels were significantly lower in cirrhosis compared to healthy subjects and decreased according to disease severity (P<.001 for all molecules). In Kaplan-Meier analysis, development of CSI was associated with low level of FCN-2 (<427 ng/mL, pLogRank=0.047) and FCN-3 (<4857 ng/mL, pLogRank=0.029), but not with MASP-2 deficiency (<100 ng/mL, pLogRank=0.306). Combined FCN deficiency was associated with increased risk of development of bacterial infections in a step-wise manner. Patients with low level of both FCNs had higher cumulative probability of CSI (63.8%) compared to those with low level of one or normal FCN (52.7% and 45.7%, pLogRank=0.016). Neither FCN serum profile, nor MASP-2 deficiency were associated with infection-related mortality.
  
  
  
  Low level of FCNs associated with hepatic insufficiency might be considered as an additional constituent of cirrhosis-associated immune dysfunction.
authors.affiliation: Department of Internal Medicine, Division of Gastroenterology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: Ildiko
authors.initials: I
authors.lastname: Foldi
authors.affiliation: Department of Internal Medicine, Division of Gastroenterology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: Tamas
authors.initials: T
authors.lastname: Tornai
authors.affiliation: Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: David
authors.initials: D
authors.lastname: Tornai
authors.affiliation: Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: Nora
authors.initials: N
authors.lastname: Sipeki
authors.affiliation: Department of Internal Medicine, Division of Gastroenterology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Vitalis
authors.affiliation: Department of Internal Medicine, Division of Gastroenterology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: Istvan
authors.initials: I
authors.lastname: Tornai
authors.affiliation: Institute of Surgery, Faculty of Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: Tamas
authors.initials: T
authors.lastname: Dinya
authors.affiliation: Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: Peter
authors.initials: P
authors.lastname: Antal-Szalmas
authors.affiliation: Department of Internal Medicine, Division of Gastroenterology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: Maria
authors.identifier: 0000-0003-3662-4010
authors.initials: M
authors.lastname: Papp
mesh_terms: D001424:Bacterial Infections / Q000097:blood / Q000175:diagnosis / Q000382:microbiology* / Q000401:mortality; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D003167:Complement Activation; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006023:Glycoproteins / Q000097:blood*; D006801:Humans; D053208:Kaplan-Meier Estimate; D037102:Lectins / Q000097:blood*; D008103:Liver Cirrhosis / Q000097:blood / Q000150:complications* / Q000175:diagnosis / Q000401:mortality; D008297:Male; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000032:analysis*; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D000097604:Ficolins
chemical_list: D015415:Biomarkers; D006023:Glycoproteins; D037102:Lectins; D050606:Mannose-Binding Protein-Associated Serine Proteases; D000097604:Ficolins; C109662:FCN3 protein, human; C105296:MASP2 protein, human
keywords: bacterial infection; cirrhosis; ficolin; mannan-binding lectin serine protease; mortality