Lectin-complement pathway molecules are decreased in patients with cirrhosis and constitute the risk of bacterial infections

Ildiko Foldi, Tamas Tornai, David Tornai, Nora Sipeki, Zsuzsanna Vitalis, Istvan Tornai, Tamas Dinya, P. Antal-Szalmás, M. Papp

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background & Aims: 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. Methods: 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). Results: 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. Conclusions: Low level of FCNs associated with hepatic insufficiency might be considered as an additional constituent of cirrhosis-associated immune dysfunction.

Original languageEnglish
JournalLiver International
DOIs
Publication statusAccepted/In press - 2017

Fingerprint

Mannose-Binding Lectin Complement Pathway
Bacterial Infections
Fibrosis
Mannose-Binding Protein-Associated Serine Proteases
Lectins
Healthy Volunteers
ficolin
Hepatic Insufficiency
Kaplan-Meier Estimate
Serum
Observational Studies

Keywords

  • Bacterial infection
  • Cirrhosis
  • Ficolin
  • Mannan-binding lectin serine protease
  • Mortality

ASJC Scopus subject areas

  • Hepatology

Cite this

Lectin-complement pathway molecules are decreased in patients with cirrhosis and constitute the risk of bacterial infections. / Foldi, Ildiko; Tornai, Tamas; Tornai, David; Sipeki, Nora; Vitalis, Zsuzsanna; Tornai, Istvan; Dinya, Tamas; Antal-Szalmás, P.; Papp, M.

In: Liver International, 2017.

Research output: Contribution to journalArticle

Foldi, Ildiko ; Tornai, Tamas ; Tornai, David ; Sipeki, Nora ; Vitalis, Zsuzsanna ; Tornai, Istvan ; Dinya, Tamas ; Antal-Szalmás, P. ; Papp, M. / Lectin-complement pathway molecules are decreased in patients with cirrhosis and constitute the risk of bacterial infections. In: Liver International. 2017.
@article{960cfd89a84d410a9ad25f65320d2edb,
title = "Lectin-complement pathway molecules are decreased in patients with cirrhosis and constitute the risk of bacterial infections",
abstract = "Background & Aims: 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. Methods: 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). Results: 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. Conclusions: Low level of FCNs associated with hepatic insufficiency might be considered as an additional constituent of cirrhosis-associated immune dysfunction.",
keywords = "Bacterial infection, Cirrhosis, Ficolin, Mannan-binding lectin serine protease, Mortality",
author = "Ildiko Foldi and Tamas Tornai and David Tornai and Nora Sipeki and Zsuzsanna Vitalis and Istvan Tornai and Tamas Dinya and P. Antal-Szalm{\'a}s and M. Papp",
year = "2017",
doi = "10.1111/liv.13368",
language = "English",
journal = "Liver International",
issn = "1478-3223",
publisher = "Wiley-Blackwell",

}

TY - JOUR

T1 - Lectin-complement pathway molecules are decreased in patients with cirrhosis and constitute the risk of bacterial infections

AU - Foldi, Ildiko

AU - Tornai, Tamas

AU - Tornai, David

AU - Sipeki, Nora

AU - Vitalis, Zsuzsanna

AU - Tornai, Istvan

AU - Dinya, Tamas

AU - Antal-Szalmás, P.

AU - Papp, M.

PY - 2017

Y1 - 2017

N2 - Background & Aims: 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. Methods: 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). Results: 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. Conclusions: Low level of FCNs associated with hepatic insufficiency might be considered as an additional constituent of cirrhosis-associated immune dysfunction.

AB - Background & Aims: 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. Methods: 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). Results: 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. Conclusions: Low level of FCNs associated with hepatic insufficiency might be considered as an additional constituent of cirrhosis-associated immune dysfunction.

KW - Bacterial infection

KW - Cirrhosis

KW - Ficolin

KW - Mannan-binding lectin serine protease

KW - Mortality

UR - http://www.scopus.com/inward/record.url?scp=85014248280&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85014248280&partnerID=8YFLogxK

U2 - 10.1111/liv.13368

DO - 10.1111/liv.13368

M3 - Article

C2 - 28109038

AN - SCOPUS:85014248280

JO - Liver International

JF - Liver International

SN - 1478-3223

ER -