van den Berg J W, Hepkema B G, Geertsma A, Koëter G H, Postma D S, de Boer W J, Lems S P, van der Bij W
Department of Pulmonary Diseases, University Hospital Groningen, The Netherlands.
Transplantation. 2001 Feb 15;71(3):368-73. doi: 10.1097/00007890-200102150-00005.
The importance of HLA mismatch in determining long-term outcome in lung transplantation remains largely uncertain.
A retrospective analysis of 102 consecutive primary lung transplants was performed to identify risk factors for poor long-term outcome after lung transplantation defined as graft survival and bronchiolitis obliterans syndrome (BOS) stage I and II. Variables included were patient characteristics (age, sex, prior diagnosis), the number of HLA mismatches between donor and recipient, cold ischemic time, cytomegalovirus serologic concordance, number of acute rejections, and time to first rejection. Variables carrying significance in a univariate analysis were subjected to a proportional hazard regression analysis.
In the multivariate analysis, an increased number of acute rejections correlated positively with decreased graft survival (risk ratio [RR] = 1.25; 95% confidence interval [CI], 1.05-1.5; P = 0.011), development of BOS stage I (RR = 1.36/episode; 95% CI, 1.16-1.58;P < 0.001), and BOS stage II (RR = 1.42/episode; 95% CI, 1.2-1.67; P < 0.001). An increased time to rejection correlated positively with reduced graft survival (RR = 1.03/day; 95% CI, 1.01-1.06; P = 0.02), and BOS stage I and II (both RR = 1.04/day; 95% CI, 1.01-1.07; P < 0.005). Compared with 2 HLA-DR mismatches, 0 or 1 mismatch was associated with improved graft survival (RR = 0.43; 95% CI, 0.19-0.98; P = 0.045) and protected against development of BOS stage I (RR = 0.47; 95% CI, 0.23-0.98; P = 0.044) and BOS stage II (RR = 0.35; 95% CI, 0.15-0.83; P = 0.017).
HLA-DR mismatching appears to be a risk factor for the development of BOS and graft loss. Improved outcome after lung transplantation might be achieved with prospective matching for HLA-DR. Alternatively, the amount and type of immunosuppressive drugs may be guided by the degree of HLA-DR (mis)matching.
HLA错配在决定肺移植长期预后中的重要性在很大程度上仍不确定。
对102例连续的初次肺移植进行回顾性分析，以确定肺移植后长期预后不良的危险因素，长期预后不良定义为移植物存活及闭塞性细支气管炎综合征（BOS）I期和II期。纳入的变量包括患者特征（年龄、性别、既往诊断）、供体与受体之间HLA错配的数量、冷缺血时间、巨细胞病毒血清学一致性、急性排斥反应的次数以及首次排斥反应的时间。在单因素分析中有显著意义的变量进行比例风险回归分析。
在多因素分析中，急性排斥反应次数增加与移植物存活率降低呈正相关（风险比[RR]=1.25；95%置信区间[CI]，1.05 - 1.5；P = 0.011）、BOS I期的发生（RR = 1.36/次；95% CI，1.16 - 1.58；P < 0.001）以及BOS II期的发生（RR = 1.42/次；95% CI，1.2 - 1.67；P < 0.001）。排斥反应发生时间延长与移植物存活率降低呈正相关（RR = 1.03/天；95% CI，1.01 - 1.06；P = 0.02），以及与BOS I期和II期（RR均 = 1.04/天；95% CI，1.01 - 1.07；P < 0.005）。与2个HLA - DR错配相比，0个或1个错配与移植物存活率提高相关（RR = 0.43；95% CI，0.19 - 0.98；P = 0.045），并可预防BOS I期的发生（RR = 0.47；95% CI，0.23 - 0.98；P = 0.044）和BOS II期的发生（RR = 0.35；95% CI，0.15 - 0.83；P = 0.017）。
HLA - DR错配似乎是BOS发生和移植物丢失的危险因素。通过对HLA - DR进行前瞻性配型可能实现肺移植后更好的预后。或者，免疫抑制药物的用量和类型可根据HLA - DR（错）配型程度来指导。
