Brugière Olivier, Thabut Gabriel, Suberbielle Caroline, Reynaud-Gaubert Martine, Thomas Pascal, Pison Christophe, Saint Raymond Christel, Mornex Jean-François, Bertocchi Michèle, Dromer Claire, Velly Jean-François, Stern Marc, Philippe Bruno, Dauriat Gaëlle, Biondi Giuseppina, Castier Yves, Fournier Michel
Hôpital Bichat, Paris, France.
J Heart Lung Transplant. 2008 Jun;27(6):628-34. doi: 10.1016/j.healun.2008.02.013.
Recent data strongly suggest that human leukocyte antigen (HLA) mismatching has a negative impact on development of bronchiolitis obliterans syndrome (BOS) and survival after lung transplantation (LTx). Because HLA matching is sometimes achieved by extending ischemic time in other solid-organ transplantation models and ischemic time is a risk factor per se for death after LTx, we sought to compare the theoretical benefit of HLA matching with the negative impact of lengthened ischemic time.
In this collaborative study we compared the relative impact of HLA mismatching and ischemic time on BOS and survival in 182 LTx recipients.
Using multivariate analyses, we observed a lower incidence of BOS (hazard ratio [HR] = 1.70, 95% confidence interval [CI]: 1.1 to 2.7, p = 0.03) and enhanced survival (HR = 1.91, 95% CI: 1.24 to 2.92, p = 0.01) in patients with zero or one HLA-A mismatch compared with those having two HLA-A mismatches. This beneficial effect on survival was equivalent to a reduction of ischemic time of 168 minutes.
We observed a reduced incidence of BOS and a better survival rate in patients well-matched at the HLA-A locus, associated with an opposite effect of an enhanced ischemic time. This suggests that graft ischemic time should be taken into account in future studies of prospective HLA matching in LTx.
近期数据有力地表明,人类白细胞抗原(HLA)错配会对闭塞性细支气管炎综合征(BOS)的发展以及肺移植(LTx)后的生存率产生负面影响。由于在其他实体器官移植模型中,有时可通过延长缺血时间来实现HLA匹配,且缺血时间本身就是LTx后死亡的一个危险因素,因此我们试图比较HLA匹配的理论益处与延长缺血时间的负面影响。
在这项合作研究中,我们比较了182例LTx受者中HLA错配和缺血时间对BOS及生存率的相对影响。
通过多变量分析,我们观察到与有两个HLA - A错配的患者相比,HLA - A错配为零或一个的患者发生BOS的发生率较低(风险比[HR]=1.70,95%置信区间[CI]:1.1至2.7,p = 0.03)且生存率提高(HR = 1.91,95% CI:1.24至2.92,p = 0.01)。这种对生存的有益影响相当于将缺血时间减少168分钟。
我们观察到HLA - A位点匹配良好的患者BOS发生率降低且生存率更高,同时缺血时间延长会产生相反的影响。这表明在未来LTx前瞻性HLA匹配研究中应考虑移植物缺血时间。