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
RBWH Foundation Clinical Research Centre, Royal Brisbane and Women's Hospital and Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
Clin Infect Dis. 2009 Feb 15;48(4):410-7. doi: 10.1086/596313.
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.
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.
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.
Recipients of MBL-deficient livers have almost a 3-fold greater likelihood of developing CSI and may benefit from MBL replacement.
甘露糖结合凝集素（MBL）是天然免疫的重要介质，主要由肝脏合成。MBL水平低很常见，主要是由于编码MBL的基因（MBL2）存在多态性，并且与感染风险增加相关，尤其是在免疫功能受损时。我们报告了一项大型回顾性研究，该研究探讨了原位肝移植后MBL状态与具有临床意义的感染之间的关联。
研究了102对供体-受体原位肝移植配对。检测了MBL2启动子和编码区的5种多态性。使用甘露聚糖结合和C4沉积试验测量移植前后获得的血清样本中的MBL水平。在生存分析中，考虑竞争风险，研究了根据血清MBL水平和MBL2基因型评估的MBL状态与移植后首次发生具有临床意义的感染（CSI）的时间之间的关联。
原位肝移植后的中位随访时间为4年。36%的受者在移植后发生了CSI。供体中存在MBL2编码突变与受者的CSI显著相关；肝脏缺陷的受者感染的累积发生率为55%，而野生型肝脏受者为32%（P = 0.002）。感染与受者MBL2基因型无关。原位肝移植后低MBL水平（甘露聚糖结合<1μg/mL或C4沉积<0.2 C4 U/μL）也与CSI相关（累积发生率分别为52%对20%，P = 0.003；以及累积发生率为54%对24%，P = 0.007）。在多变量分析中，供体MBL2编码区的突变（风险比，2.8；P = 0.005）和使用巨细胞病毒预防措施（风险比，2.6；P = 0.005）与CSI独立相关。
MBL缺陷肝脏的受者发生CSI的可能性几乎高2倍，可能从MBL替代中获益。
