Donor Mannose-Binding Lectin Deficiency Increases the Likelihood of Clinically Significant Infection after Liver Transplantation

Background. Mannose-binding lectin (MBL) is an important mediator of innate immunity and is synthesized primarily by the liver. Low MBL levels are common, are due primarily to polymorphisms in the gene encoding MBL (MBL2), and are associated with an increased risk of infection, particularly when imm...

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Bibliographic Details
Published in:Clinical infectious diseases 2009-02, Vol.48 (4), p.410-417
Main Authors: Worthley, Daniel L., Johnson, Douglas F., Eisen, Damon P., Dean, Melinda M., Heatley, Susan L., Tung, John-Paul, Scott, Justin, Padbury, Robert T. A., Harley, Hugh A., Bardy, Peter G., Angus, Peter W., Mullighan, Charles G.
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Alleles
Articles and Commentaries
Binding sites
Child
Communicable Diseases - epidemiology
Cytomegalovirus
Female
Genetic mutation
Genetic Predisposition to Disease - epidemiology
Genotypes
Glycoproteins
Haplotypes
Humans
Infections
Lectins
Liver
Liver transplantation
Liver Transplantation - adverse effects
Male
Mannose-Binding Lectin - deficiency
Middle Aged
Multivariate analysis
Open Reading Frames - genetics
Polymorphism
Polymorphism, Genetic
Promoter Regions, Genetic
Retrospective Studies
Risk Factors
Studies
Survival analysis
Tissue Donors
Transplantation
Transplants & implants
Young Adult
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Summary:Background. Mannose-binding lectin (MBL) is an important mediator of innate immunity and is synthesized primarily by the liver. Low MBL levels are common, are due primarily to polymorphisms in the gene encoding MBL (MBL2), and are associated with an increased risk of infection, particularly when immunity is compromised. We report a large, retrospective study that examined the association between MBL status and clinically significant infection following orthotopic liver transplantation. Methods. One hundred two donor-recipient orthotopic liver transplantation pairs were studied. Five polymorphisms in the promoter and coding regions of MBL2 were examined. MBL levels were measured, using the mannan-binding and C4-deposition assays, in serum samples obtained before and after transplantation. Associations between MBL status, as assessed by serum MBL levels and MBL2 genotype, and time to first clinically significant infection (CSI) after transplantation were examined in survival analysis with consideration of competing risks. Results. The median duration of follow-up after orthotopic liver transplantation was 4 years. Thirty-six percent of recipients developed CSI after transplantation. The presence of MBL2 coding mutations in the donor was significantly associated with CSI in the recipient; the cumulative incidence function of infection was 55% in recipients of deficient livers, compared with 32% for recipients of wild-type livers (P=.002). Infection was not associated with recipient MBL2 genotype. Low MBL levels after orthotopic liver transplantation levels (mannan-binding
ISSN:1058-4838
1537-6591
DOI:10.1086/596313