INSERM UMR1152, Bichat Hospital, Paris-Diderot University, Paris, France.
Division of Genetics, Bichat Hospital, Paris-Diderot University, Paris. France.
Transplantation. 2018 Aug;102(8):1382-1390. doi: 10.1097/TP.0000000000002143.
Club Cell Secretory Protein (CCSP) G38A polymorphism has recently been involved in lung epithelial susceptibility to external injuries. Lung transplantation (LT) is currently limited by ischemia-reperfusion injury leading to primary graft dysfunction (PGD). We thus hypothesized that donor CCSP G38A polymorphism might impact the risk of PGD after LT.
We focused on LT included in the French multicentric Cohort in Lung Transplantation (COLT), performed between January 2009 and December 2014, and associated with preoperative blood samples from the donor and the recipient. Characteristics of the donors, recipients, procedures, early and late outcomes were prospectively recorded in COLT. The CCSP serum concentration and CCSP gene G38A polymorphism were retrospectively determined in a blind manner. Their association with grade 3 PGD was studied in univariate and multivariate analysis.
The study group included 104 LT donors and recipients, 84 with grade 0 to 2 PGD and 20 with grade 3 PGD. Preoperative CCSP serum concentration was significantly higher in the donors (median, 22.54 ng/mL; interquartile range, 9.6-43.9) than in the recipients (median, 7.03 ng/mL; interquartile range, 0.89-19.2; P < 0.001) but none impacted the risk of grade 3 PGD (P = 0.93 and P = 0.69, respectively). Donor CCSP G38A polymorphism was associated with a decreased risk of grade 3 PGD in univariate (AG + AA 3/21 = 14.2% vs GG 10/26 = 38.4%, P = 0.044) and multivariate analysis (odds ratio associated with AG + AA, 0.22; 95% confidence interval, 0.041-0.88; P = 0.045), but recipient CCSP G38A polymorphism was not.
Donor CCSP G38A polymorphism is associated with a decreased risk of severe PGD after LT in the COLT study. These findings should be confirmed in the frame of a prospective study.
最近，俱乐部细胞分泌蛋白（CCSP）G38A 多态性与肺上皮对外伤的易感性有关。肺移植（LT）目前受到缺血再灌注损伤导致原发性移植物功能障碍（PGD）的限制。因此，我们假设供体 CCSP G38A 多态性可能影响 LT 后 PGD 的风险。
我们专注于 2009 年 1 月至 2014 年 12 月期间在法国多中心肺移植队列（COLT）中进行的 LT，并与供体和受体的术前血液样本相关联。前瞻性记录 COLT 中的供体、受体、手术、早期和晚期结果的特征。以盲法方式回顾性确定 CCSP 血清浓度和 CCSP 基因 G38A 多态性。在单变量和多变量分析中研究它们与 3 级 PGD 的关系。
研究组包括 104 例 LT 供体和受体，84 例为 0 至 2 级 PGD，20 例为 3 级 PGD。供体的术前 CCSP 血清浓度明显高于受体（中位数，22.54ng/ml；四分位距，9.6-43.9）（中位数，7.03ng/ml；四分位距，0.89-19.2；P<0.001），但均未增加 3 级 PGD 的风险（P=0.93 和 P=0.69）。在单变量（AG+AA3/21=14.2%比 GG10/26=38.4%，P=0.044）和多变量分析（与 AG+AA 相关的优势比，0.22；95%置信区间，0.041-0.88；P=0.045）中，供体 CCSP G38A 多态性与 3 级 PGD 的风险降低相关，但受体 CCSP G38A 多态性没有。
COLT 研究中，供体 CCSP G38A 多态性与 LT 后严重 PGD 的风险降低有关。这些发现应在前瞻性研究中得到证实。
