Schulman L L, Weinberg A D, McGregor C, Galantowicz M E, Suciu-Foca N M, Itescu S
Departments of Medicine, Pathology, and Surgery, College of Physicians and Surgeons of Columbia University, New York, New York, USA.
Am J Respir Crit Care Med. 1998 Jun;157(6 Pt 1):1833-7. doi: 10.1164/ajrccm.157.6.9707007.
Early high-grade acute rejections (pathologic grade A2 or A3) in recipients of lung allografts are a major risk factor for the subsequent development of obliterative bronchiolitis (OB). We analyzed the risk factors for high-grade acute rejections in 152 recipients of single (100) or bilateral (52) lung allografts transplanted at our institution between 1990 and 1996. Using Kaplan-Meier product limit estimate analysis, there was a 50% probability of grade A2 or A3 rejection by 1 yr after transplant. By univariate analysis, the only significant predictor of early high-grade rejections was the presence of one or more mismatches at the HLA-DR locus (p = 0.038). This association was confirmed using the Cox proportional hazards model for multivariable analysis, with HLA-DR locus mismatch being the only risk factor identified for high-grade rejection (p = 0.036). Using repeated rejection analysis, recipients with one or more matches at the HLA-DR locus had a lower cumulative rate of grade A2 or A3 rejections during the first year compared with recipients with no matches at the HLA-DR locus (0.73 versus 1.32). In addition, recipients with one or more HLA-B locus matches had a lower cumulative rate of grade A2 or A3 rejections in the first year than did recipients with no matches at the HLA-B locus (0.59 versus 1.30). These results indicate that mismatches between donors and recipients at the HLA-DR and HLA-B loci are important risk factors for early high-grade rejections after lung transplantation. Immunosuppressive protocols that are more effective in preventing recipient T-cell activation by donor alloantigens are likely to reduce the rate of high-grade acute rejections in recipients of lung transplants, and may directly impact on the time to onset of OB.
肺移植受者早期的高级别急性排斥反应（病理分级为A2或A3）是随后发生闭塞性细支气管炎（OB）的主要危险因素。我们分析了1990年至1996年间在我们机构接受单肺（100例）或双肺（52例）移植的152例受者发生高级别急性排斥反应的危险因素。使用Kaplan-Meier乘积限估计分析，移植后1年时发生A2或A3级排斥反应的概率为50%。单因素分析显示，早期高级别排斥反应的唯一显著预测因素是HLA-DR位点存在一个或多个错配（p = 0.038）。使用Cox比例风险模型进行多变量分析证实了这种关联，HLA-DR位点错配是确定的高级别排斥反应的唯一危险因素（p = 0.036）。通过重复排斥反应分析，与HLA-DR位点无匹配的受者相比，HLA-DR位点有一个或多个匹配的受者在第一年期间A2或A3级排斥反应的累积发生率较低（0.73对1.32）。此外，HLA-B位点有一个或多个匹配的受者在第一年的A2或A3级排斥反应累积发生率低于HLA-B位点无匹配的受者（0.59对1.30）。这些结果表明，供体和受体之间在HLA-DR和HLA-B位点的错配是肺移植后早期高级别排斥反应的重要危险因素。在预防受体T细胞被供体同种异体抗原激活方面更有效的免疫抑制方案可能会降低肺移植受者高级别急性排斥反应的发生率，并可能直接影响OB的发病时间。
