title: Donor mannose-binding lectin deficiency increases the likelihood of clinically significant infection after liver transplantation.
abstract: 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 <1 microg/mL or C4 deposition <0.2 C4 U/microL) were also associated with CSI (cumulative incidence function, 52% vs. 20%, P = .003; and cumulative incidence function, 54% vs. 24%, P = .007, respectively). In multivariate analysis, mutation in the MBL2 coding region of the donor (hazard ratio, 2.8; P = .005) and the use of cytomegalovirus prophylaxis (hazard ratio, 2.6; P = .005) were independently associated with CSI.
  
  
  CONCLUSIONS
  Recipients of MBL-deficient livers have almost a 3-fold greater likelihood of developing CSI and may benefit from MBL replacement.
authors.affiliation: RBWH Foundation Clinical Research Centre, Royal Brisbane and Women's Hospital and Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Worthley
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Johnson
authors.forename: Damon P
authors.initials: DP
authors.lastname: Eisen
authors.forename: Melinda M
authors.initials: MM
authors.lastname: Dean
authors.forename: Susan L
authors.initials: SL
authors.lastname: Heatley
authors.forename: John-Paul
authors.initials: JP
authors.lastname: Tung
authors.forename: Justin
authors.initials: J
authors.lastname: Scott
authors.forename: Robert T A
authors.initials: RT
authors.lastname: Padbury
authors.forename: Hugh A
authors.initials: HA
authors.lastname: Harley
authors.forename: Peter G
authors.initials: PG
authors.lastname: Bardy
authors.forename: Peter W
authors.initials: PW
authors.lastname: Angus
authors.forename: Charles G
authors.initials: CG
authors.lastname: Mullighan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D003141:Communicable Diseases / Q000453:epidemiology*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D006801:Humans; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D037601:Mannose-Binding Lectin / Q000172:deficiency*; D008875:Middle Aged; D016366:Open Reading Frames / Q000235:genetics; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012189:Retrospective Studies; D012307:Risk Factors; D014019:Tissue Donors; D055815:Young Adult
chemical_list: C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin