Mullighan Charles G, Heatley Sue, Doherty Kathleen, Szabo Ferenc, Grigg Andrew, Hughes Timothy P, Schwarer Anthony P, Szer Jeff, Tait Brian D, Bik To L, Bardy Peter G
Research and Development, Australian Red Cross Blood Service, South Australia.
Blood. 2002 May 15;99(10):3524-9. doi: 10.1182/blood.v99.10.3524.
Life-threatening complications such as graft versus host disease and infection remain major barriers to the success of allogeneic hemopoietic stem cell transplantation (SCT). While pretransplantation conditioning and posttransplantation immunosuppression are important risk factors for infection, the reasons that similarly immunosuppressed transplant recipients show marked variation in frequency of infection after allogeneic SCT are unclear. Mannose-binding lectin (MBL) deficiency is a risk factor for infection in other situations where immunity is compromised. We investigated associations between MBL2 gene polymorphisms and risk of major infection following allogeneic SCT. Ninety-seven related allogeneic donor-recipient pairs were studied. Clinical data including survival, days of fever, graft versus host disease incidence and severity, and infection were collected by case note review. Five single-nucleotide polymorphisms in the MBL2 gene were genotyped using the polymerase chain reaction and sequence-specific primers. MBL2 coding mutations were associated with an increased risk of major infection following transplantation. This association was seen for donor (P =.002, odds ratio [OR] 4.1) and recipient (P =.04, OR 2.6) MBL2 genotype. MBL2 promoter variants were also associated with major infection. The high-producing haplotype HYA was associated with a markedly reduced risk of infection (recipient HYA P =.0001, OR 0.16; donor HYA P =.001, OR 0.23). Donor MBL2 coding mutations and recipient HYA haplotype were independently associated with infection in multivariate analysis. These results suggest that MBL2 genotype influences the risk of infection following allogeneic SCT and that both donor and recipient MBL2 genotype are important. These findings raise the possibility that MBL replacement therapy may be useful following transplantation.
移植物抗宿主病和感染等危及生命的并发症仍然是异基因造血干细胞移植（SCT）成功的主要障碍。虽然移植前预处理和移植后免疫抑制是感染的重要危险因素，但同样处于免疫抑制状态的移植受者在异基因SCT后感染频率出现显著差异的原因尚不清楚。甘露糖结合凝集素（MBL）缺乏是免疫功能受损的其他情况下感染的危险因素。我们研究了MBL2基因多态性与异基因SCT后严重感染风险之间的关联。对97对相关的异基因供受者进行了研究。通过病例记录回顾收集包括生存情况、发热天数、移植物抗宿主病发生率和严重程度以及感染情况在内的临床数据。使用聚合酶链反应和序列特异性引物对MBL2基因中的五个单核苷酸多态性进行基因分型。MBL2编码突变与移植后严重感染风险增加相关。供体（P = 0.002，优势比[OR] 4.1）和受体（P = 0.04，OR 2.6）的MBL2基因型均显示出这种关联。MBL2启动子变体也与严重感染相关。高产生单倍型HYA与感染风险显著降低相关（受体HYA P = 0.0001，OR 0.16；供体HYA P = 0.001，OR 0.23）。在多变量分析中，供体MBL2编码突变和受体HYA单倍型与感染独立相关。这些结果表明MBL2基因型影响异基因SCT后的感染风险，并且供体和受体的MBL2基因型都很重要。这些发现增加了移植后MBL替代疗法可能有用的可能性。
