Does the donor mannose-binding lectin genotype really predict the risk of bacterial infections after liver transplantation?
Authors: Lilian A. Curvelo, Emmeloes de Mare-Bredemeijer, Ilse de Canck, Martine van Thielen, Geert Kazemier, Herold Metselaar, Jaap Kwekkeboom
Journal: Hepatology (2010)

With great interest, we read the recent article by De Rooij et al.1 and the accompanying editorial.2 The authors showed that functional single-nucleotide polymorphisms within donor genes involved in the lectin complement pathway [mannose-binding lectin 2 (MBL2), ficolin 2, and mannan-binding lectin-associated serine protease 2 (MASP2)] determine the risk of bacterial infections after liver transplantation (LT). Although this is the first study associating single-nucleotide polymorphisms in ficolin 2 and MASP2 with the risk of infection after LT, the value of the donor MBL2 genotype as a risk factor for infection after LT is supported by two other studies.3, 4 However, a fourth study5 found no difference in the overall rate of infections between patients who received liver transplants from donors with insufficient MBL genotypes and those who received liver transplants from donors with sufficient MBL genotypes; although there was a higher incidence of septic shock after transplantation with MBL-insufficient livers. Moreover, the published studies used different ways to stratify MBL genotypes into groups with MBL serum levels predicted to be sufficient or insufficient. Donor YA/YA and YA/XA genotypes result in high serum MBL2 levels, O/O and XA/O genotypes are almost MBL2-deficient, and YA/O and XA/XA genotypes are associated with intermediate MBL2 serum levels after LT.4 Although De Rooij et al. used a strict definition of MBL insufficiency and considered only O/O and XA/O genotypes to be MBL-insufficient, Worthley et al.4 also considered the intermediate XA/XA genotype to be MBL-insufficient, and the two other studies3, 5 also included the second intermediate genotype (YA/O) in the MBL-insufficient group. Therefore, the value of the donor MBL genotype and the method of its interpretation for the early identification of LT patients at risk of infectious complications are not established yet. We studied the predictive value of donor MBL genotyping for bacterial infections in our own center. The MBL genotypes of 290 donor livers used for orthotopic transplantation between 1987 and 2010 were determined. Notably, this cohort represents the largest single-center cohort of LT patients in which associations between the donor MBL2 genotype and bacterial infections have been analyzed. In three different ways, we categorized donor livers as MBL-sufficient or MBL-insufficient according to the stratification systems used in the cited studies, and we analyzed associations with clinically significant and laboratory-confirmed bacterial infections occurring during the first 3 months after LT by chi-square analysis with Fisher's exact test (Table 1). Thirty-eight percent of LT recipients experienced one or more infectious episodes, and this is comparable to the numbers reported by the previous studies.1, 4, 5 Importantly, none of the three stratifications resulted in a statistically significant association between the donor MBL genotype and clinically significant infections. In addition, when we analyzed associations with site-specific infections, independently of MBL genotype stratification, we observed no significant increases in the risk of intra-abdominal infections or bacteremia in patients who underwent transplantation with MBL-insufficient livers. However, in two of the three types of MBL genotype stratification, significantly more pneumonia was diagnosed in patients who underwent transplantation with MBL-deficient livers. In conclusion, this retrospective study indicates that in our center, the donor MBL2 genotype is not helpful in predicting the risk of bacterial infection after LT. Lilian A. Curvelo M.D., Ph.D.*, Emmeloes de Mare-Bredemeijer M.D.*, Ilse de Canck M.Sc. , Martine van Thielen M.Sc. , Geert Kazemier M.D., Ph.D. , Herold Metselaar M.D., Ph.D.*, Jaap Kwekkeboom Ph.D.*, * Departments of Gastroenterology and Hepatology, Rotterdam, the Netherlands, Surgery, Erasmus MC: University Medical Center Rotterdam, Rotterdam, the Netherlands, R&D Discovery, Innogenetics NV, Zwijnaarde, Belgium.