Donor mannose-binding lectin gene polymorphisms influence the outcome of liver transplantation

Abstract

Mannose-binding lectin (MBL) is a C-type lectin produced mainly by the liver that binds to a wide range of pathogens. Polymorphisms at the promoter and exon 1 of the MBL2 gene are responsible for low serum levels of MBL and have been associated with an increased risk of infections. We prospectively analyzed 95 liver transplant recipients. Well-known functionally relevant polymorphisms of the MBL2 gene of the liver donor were examined by gene sequencing. Infectious events were collected prospectively. No differences in the incidence of infections were found according to the donor MBL2 genotypes. Survival was lower in patients receiving a liver graft from a donor with an exon 1 MBL2 variant genotype, and they had higher infection-related mortality (50% versus 14%, P = 0.040). No differences were found according to other polymorphisms involving the promoter and 5'-untranslated region. When we analyzed bacterial infection episodes, we found that patients receiving a liver from a donor with an exon 1 variant genotype had a higher incidence of septic shock (46% versus 11%, P = 0.004). Independent variables associated with graft or patient survival were as follows: receiving a graft from a donor with an exon 1 MBL2 variant genotype [adjusted hazard ratio (aHR), 9.64; 95% confidence interval (CI), 2.59-36.0], the Model for End-Stage Liver Disease score (aHR, 1.14; 95% CI, 1.05-1.23), and bacterial infections (aHR, 11.1; 95% CI, 2.73-44.9). Liver transplantation from a donor with a variant MBL2 exon 1 genotype was associated with a worse prognosis, mainly because of infections of higher severity.

Clinical immune‐monitoring strategies for predicting infection risk in solid organ transplantation

“…In addition, it remains to be clarified whether the demonstration of MBL-deficient genotypes of mbl2 or related genes (MBL-associated serine protease or ficolin-2 genes) could avoid the need for post-transplant monitoring of serum levels, as suggested by some authors. 42, 43 …”

Mannose-binding lectin deficiency confers risk for bacterial infections in a large Hungarian cohort of patients with liver cirrhosis

“…The posttransplantation serum MBL level was predicted by the hepatic and not the extrahepatic genotype [18,19]. In another study, a donor MBL2 variant genotype significantly influenced the outcome of the liver transplantation, mainly because of infectious events of higher severity [20]. Finally, in a small study, the MBL2 deficient genotype predisposed patients with hepatitis B virus induced liver cirrhosis to develop spontaneous bacterial peritonitis [21].…”

Hepatobiliary Quiz Answers—19 (2016)

“…Thus any genetic defects in innate immune system like toll like Receptors and lectin pathway make the patient highly vulnerable to infections. [48][49][50] MELD .20 is a significant risk factor for developing infection within the first 30 days after OLT. Other risk factors include albumin level \2.8 g/dL, intraoperative erythrocyte transfusion more than 6 units, intraoperative fresh frozen plasma transfusion more than 12 units, bilioenteric anastomosis, postoperative intensive care unit stay more than 6 days, and postoperative length of hospital stay more than 21 days.…”