Polymorphisms in lectin pathway genes determine their functional activity. We assessed the relationship between these polymorphic genes and clinically significant bacterial infections, i.e., sepsis, pneumonia, and intra-abdominal infection, and mortality within the first year after OLT, in relation to major risk factors in two cohorts from different transplant centers. Single-nucleotide polymorphisms in the mannose-binding lectin gene (MBL2), the ficolin-2 gene (FCN2), and the MBL-associated serine protease gene (MASP2) of recipients and donors were determined. Recipients

receiving a donor liver in the principal cohort with polymorphisms in all three components i.e., MBL2 (XA/O; O/O), FCN2+6359T, and MASP2+371A, had a cumulative risk of an infection buy AZD6738 of 75% as compared to 18% with wild-type donor livers (P = 0.002), an observation confirmed in the second cohort (P = 0.04). In addition, a genetic (mis)match between donor and

recipient Palbociclib research buy conferred a two-fold higher infection risk for each separate gene. Multivariate Cox analysis revealed a stepwise increase in infection risk with the lectin pathway gene profile of the donor (hazard ratio = 4.52; P = 8.1 × 10−6) and the donor-recipient (mis)match genotype (hazard ratio = 6.41; P = 1.9 × 10−7), independent from the other risk factors sex and antibiotic prophylaxis (hazard ratio > 1.7 and P < 0.02). Moreover, patients with a lectin pathway gene polymorphism and infection had a six-fold higher mortality 上海皓元 (P = 0.9 × 10−8), of which 80% was infection-related. Conclusion: Donor and recipient gene polymorphisms in the lectin complement pathway are major determinants of the risk of clinically significant bacterial infection and mortality after OLT. (HEPATOLOGY 2010;) The occurrence of infectious complications is a major clinical problem after orthotopic liver transplantation (OLT).1 Immunosuppressive agents that prevent graft rejection interfere with the adaptive immune response and thereby increase the susceptibility to infections. These drugs do not affect, however,

the innate immune system that is crucial for the first line of immunological defense. Lectins, humoral pattern recognition molecules of the innate immune system, recognize pathogen-associated carbohydrate motifs on microorganisms and elicit activation of multiple processes of innate immunity. In order to execute the elimination of microorganisms, these lectins, such as mannose-binding lectin (MBL) and ficolins, cooperate with phagocytes and other humoral factors, including complement. Upon pathogen binding, both lectins activate the complement system via MBL-associated serine proteases (MASPs), leading to C3b-mediated opsonization of the microorganism followed by phagocytosis and the formation of a complement membrane attack complex that directly kills the pathogen.