Mannose binding lectin gene polymorphisms confer a major risk for severe infections after liver transplantation

Lee H Bouwman; Anja Roos; Onno T Terpstra; Peter de Knijff; Bart van Hoek; Hein W Verspaget; Stefan P Berger; Mohamed R Daha; Marijke Frölich; Arno R van der Slik; Ilias I Doxiadis; Bart O Roep; Alexander F M Schaapherder

doi:10.1016/j.gastro.2005.06.049

Mannose binding lectin gene polymorphisms confer a major risk for severe infections after liver transplantation

Lee H Bouwman, Anja Roos, Onno T Terpstra, Peter de Knijff, Bart van Hoek, Hein W Verspaget, Stefan P Berger, Mohamed R Daha, Marijke Frölich, Arno R van der Slik, Ilias I Doxiadis, Bart O Roep, Alexander F M Schaapherder

Research output: Contribution to journal › Article › Academic › peer-review

107 Citations (Scopus)

Abstract

BACKGROUND & AIMS: Infection is the primary cause of death after liver transplantation. Mannose binding lectin (MBL) is a recognition molecule of the lectin pathway of complement and a key component of innate immunity. MBL variant alleles have been described in the coding region of the MBL gene, which are associated with low MBL serum concentration and impaired MBL structure and function. The aims of our study were to establish the role of the liver in production of serum MBL and to evaluate the effect of MBL variant alleles on the susceptibility to infection after liver transplantation.

METHODS: We investigated 49 patients undergoing orthotopic liver transplantation. MBL exon 1 and promoter polymorphisms were determined in patients and in liver donors. MBL serum concentration was determined before and during 1 year after transplantation. The incidence of clinically significant infections during this period was assessed.

RESULTS: Transplantation of MBL wildtype recipients with donor livers carrying MBL variant alleles resulted in a rapid and pronounced decrease of serum MBL levels. This serum conversion was associated with the disappearance of high molecular weight MBL. No indication for extrahepatic production of serum MBL could be obtained. The presence of MBL variant alleles in the MBL gene of the donor liver, but not in the recipient, was associated with a strongly increased incidence of clinically significant infections after transplantation.

CONCLUSIONS: Serum MBL is produced by the liver under strong genetic control. After liver transplantation, the MBL genotype of the donor liver is a major risk determinant for life-threatening infections.

Original language	English
Pages (from-to)	408-414
Number of pages	7
Journal	Gastroenterology
Volume	129
Issue number	2
DOIs	https://doi.org/10.1016/j.gastro.2005.06.049
Publication status	Published - Aug-2005
Externally published	Yes

Keywords

Adult
Bacterial Infections
Base Sequence
Blotting, Western
Cohort Studies
Female
Gene Expression Regulation
Genetic Markers
Graft Survival
Humans
Incidence
Liver Failure
Liver Transplantation
Male
Mannose-Binding Lectin
Middle Aged
Molecular Sequence Data
Polymerase Chain Reaction
Polymorphism, Genetic
Postoperative Complications
Probability
Prognosis
Risk Assessment
Sensitivity and Specificity
Severity of Illness Index
Statistics, Nonparametric
Survival Rate
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Access to Document

10.1016/j.gastro.2005.06.049

Handle.net

Persistent link

Embargoed Document

Mannose Binding Lectin Gene Polymorphisms Confer a Major Risk for Severe Infections After Liver Transplantation
Final publisher's version, 211 KB
Request copy

Cite this

Bouwman, L. H., Roos, A., Terpstra, O. T., de Knijff, P., van Hoek, B., Verspaget, H. W., Berger, S. P., Daha, M. R., Frölich, M., van der Slik, A. R., Doxiadis, I. I., Roep, B. O., & Schaapherder, A. F. M. (2005). Mannose binding lectin gene polymorphisms confer a major risk for severe infections after liver transplantation. Gastroenterology, 129(2), 408-414. https://doi.org/10.1016/j.gastro.2005.06.049

@article{8d83db5a5ae84ae48df62ae6509065de,

title = "Mannose binding lectin gene polymorphisms confer a major risk for severe infections after liver transplantation",

abstract = "BACKGROUND & AIMS: Infection is the primary cause of death after liver transplantation. Mannose binding lectin (MBL) is a recognition molecule of the lectin pathway of complement and a key component of innate immunity. MBL variant alleles have been described in the coding region of the MBL gene, which are associated with low MBL serum concentration and impaired MBL structure and function. The aims of our study were to establish the role of the liver in production of serum MBL and to evaluate the effect of MBL variant alleles on the susceptibility to infection after liver transplantation.METHODS: We investigated 49 patients undergoing orthotopic liver transplantation. MBL exon 1 and promoter polymorphisms were determined in patients and in liver donors. MBL serum concentration was determined before and during 1 year after transplantation. The incidence of clinically significant infections during this period was assessed.RESULTS: Transplantation of MBL wildtype recipients with donor livers carrying MBL variant alleles resulted in a rapid and pronounced decrease of serum MBL levels. This serum conversion was associated with the disappearance of high molecular weight MBL. No indication for extrahepatic production of serum MBL could be obtained. The presence of MBL variant alleles in the MBL gene of the donor liver, but not in the recipient, was associated with a strongly increased incidence of clinically significant infections after transplantation.CONCLUSIONS: Serum MBL is produced by the liver under strong genetic control. After liver transplantation, the MBL genotype of the donor liver is a major risk determinant for life-threatening infections.",

keywords = "Adult, Bacterial Infections, Base Sequence, Blotting, Western, Cohort Studies, Female, Gene Expression Regulation, Genetic Markers, Graft Survival, Humans, Incidence, Liver Failure, Liver Transplantation, Male, Mannose-Binding Lectin, Middle Aged, Molecular Sequence Data, Polymerase Chain Reaction, Polymorphism, Genetic, Postoperative Complications, Probability, Prognosis, Risk Assessment, Sensitivity and Specificity, Severity of Illness Index, Statistics, Nonparametric, Survival Rate, Comparative Study, Journal Article, Research Support, Non-U.S. Gov't",

author = "Bouwman, {Lee H} and Anja Roos and Terpstra, {Onno T} and {de Knijff}, Peter and {van Hoek}, Bart and Verspaget, {Hein W} and Berger, {Stefan P} and Daha, {Mohamed R} and Marijke Fr{\"o}lich and {van der Slik}, {Arno R} and Doxiadis, {Ilias I} and Roep, {Bart O} and Schaapherder, {Alexander F M}",

year = "2005",

month = aug,

doi = "10.1016/j.gastro.2005.06.049",

language = "English",

volume = "129",

pages = "408--414",

journal = "Gastroenterology",

issn = "0016-5085",

publisher = "W B SAUNDERS CO-ELSEVIER INC",

number = "2",

}

Bouwman, LH, Roos, A, Terpstra, OT, de Knijff, P, van Hoek, B, Verspaget, HW, Berger, SP , Daha, MR, Frölich, M, van der Slik, AR, Doxiadis, II, Roep, BO & Schaapherder, AFM 2005, 'Mannose binding lectin gene polymorphisms confer a major risk for severe infections after liver transplantation', Gastroenterology, vol. 129, no. 2, pp. 408-414. https://doi.org/10.1016/j.gastro.2005.06.049

TY - JOUR

T1 - Mannose binding lectin gene polymorphisms confer a major risk for severe infections after liver transplantation

AU - Bouwman, Lee H

AU - Roos, Anja

AU - Terpstra, Onno T

AU - de Knijff, Peter

AU - van Hoek, Bart

AU - Verspaget, Hein W

AU - Berger, Stefan P

AU - Daha, Mohamed R

AU - Frölich, Marijke

AU - van der Slik, Arno R

AU - Doxiadis, Ilias I

AU - Roep, Bart O

AU - Schaapherder, Alexander F M

PY - 2005/8

Y1 - 2005/8

N2 - BACKGROUND & AIMS: Infection is the primary cause of death after liver transplantation. Mannose binding lectin (MBL) is a recognition molecule of the lectin pathway of complement and a key component of innate immunity. MBL variant alleles have been described in the coding region of the MBL gene, which are associated with low MBL serum concentration and impaired MBL structure and function. The aims of our study were to establish the role of the liver in production of serum MBL and to evaluate the effect of MBL variant alleles on the susceptibility to infection after liver transplantation.METHODS: We investigated 49 patients undergoing orthotopic liver transplantation. MBL exon 1 and promoter polymorphisms were determined in patients and in liver donors. MBL serum concentration was determined before and during 1 year after transplantation. The incidence of clinically significant infections during this period was assessed.RESULTS: Transplantation of MBL wildtype recipients with donor livers carrying MBL variant alleles resulted in a rapid and pronounced decrease of serum MBL levels. This serum conversion was associated with the disappearance of high molecular weight MBL. No indication for extrahepatic production of serum MBL could be obtained. The presence of MBL variant alleles in the MBL gene of the donor liver, but not in the recipient, was associated with a strongly increased incidence of clinically significant infections after transplantation.CONCLUSIONS: Serum MBL is produced by the liver under strong genetic control. After liver transplantation, the MBL genotype of the donor liver is a major risk determinant for life-threatening infections.

AB - BACKGROUND & AIMS: Infection is the primary cause of death after liver transplantation. Mannose binding lectin (MBL) is a recognition molecule of the lectin pathway of complement and a key component of innate immunity. MBL variant alleles have been described in the coding region of the MBL gene, which are associated with low MBL serum concentration and impaired MBL structure and function. The aims of our study were to establish the role of the liver in production of serum MBL and to evaluate the effect of MBL variant alleles on the susceptibility to infection after liver transplantation.METHODS: We investigated 49 patients undergoing orthotopic liver transplantation. MBL exon 1 and promoter polymorphisms were determined in patients and in liver donors. MBL serum concentration was determined before and during 1 year after transplantation. The incidence of clinically significant infections during this period was assessed.RESULTS: Transplantation of MBL wildtype recipients with donor livers carrying MBL variant alleles resulted in a rapid and pronounced decrease of serum MBL levels. This serum conversion was associated with the disappearance of high molecular weight MBL. No indication for extrahepatic production of serum MBL could be obtained. The presence of MBL variant alleles in the MBL gene of the donor liver, but not in the recipient, was associated with a strongly increased incidence of clinically significant infections after transplantation.CONCLUSIONS: Serum MBL is produced by the liver under strong genetic control. After liver transplantation, the MBL genotype of the donor liver is a major risk determinant for life-threatening infections.

KW - Adult

KW - Bacterial Infections

KW - Base Sequence

KW - Blotting, Western

KW - Cohort Studies

KW - Female

KW - Gene Expression Regulation

KW - Genetic Markers

KW - Graft Survival

KW - Humans

KW - Incidence

KW - Liver Failure

KW - Liver Transplantation

KW - Male

KW - Mannose-Binding Lectin

KW - Middle Aged

KW - Molecular Sequence Data

KW - Polymerase Chain Reaction

KW - Polymorphism, Genetic

KW - Postoperative Complications

KW - Probability

KW - Prognosis

KW - Risk Assessment

KW - Sensitivity and Specificity

KW - Severity of Illness Index

KW - Statistics, Nonparametric

KW - Survival Rate

KW - Comparative Study

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.gastro.2005.06.049

DO - 10.1016/j.gastro.2005.06.049

M3 - Article

C2 - 16083697

SN - 0016-5085

VL - 129

SP - 408

EP - 414

JO - Gastroenterology

JF - Gastroenterology

IS - 2

ER -

Mannose binding lectin gene polymorphisms confer a major risk for severe infections after liver transplantation

Abstract

Keywords

Access to Document

Handle.net

Embargoed Document

Fingerprint

Cite this