Itescu S, Tung T C, Burke E M, Weinberg A D, Mancini D, Michler R E, Suciu-Foca N M, Rose E A
College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA.
Lancet. 1998 Jul 25;352(9124):263-70. doi: 10.1016/S0140-6736(98)09475-6.
Transplant-related coronary-artery disease (TCAD) develops frequently in cardiac-allograft recipients, and limits long-term survival. We examined the relation between this disorder and cumulative frequency of high-grade rejection, and investigated whether concomitant use of three immunological factors at the time of a low-grade endomyocardial biopsy can predict progression to high-grade rejection.
We investigated the relation between the cumulative annual frequency of high-grade rejection and TCAD in 198 recipients of cardiac transplantation between 1992 and 1996 by means of Kaplan-Meier actuarial life-tables. Endomyocardial biopsy, lymphocyte-growth assays, and anti-HLA antibody measurements were compiled over 12 months in 102 patients during their first post-transplant year. We calculated predictive values for high-grade rejection within 90 days by chi2, Kaplan Meier survival curves, and by multivariable logistic regression analyses.
We found a direct correlation between cumulative annual frequency of rejection and TCAD onset with highest risk in those with more than 0.75 rejections per year (p=0.0002). After a low-grade endomyocardial biopsy (0 or 1A), one or more donor-recipient HLA-DR matches protected against high-grade rejections (p<0.001). Among individuals with one or two DR matches, the negative predictive value for progression from a low-grade biopsy to a high-grade rejection was 87% in the presence of a negative lymphocyte-growth assay. Among individuals with no DR matches, the presence of either a positive lymphocyte-growth assay or IgG anti-major-histocompatibility complex (MHC) class II antibodies was independently associated with high probability of progression to rejection (64% and 66%, respectively, p<0.0005). When both assays were positive, concomitantly with a low-grade endomyocardial biopsy, the positive predictive value for progression to a high-grade rejection was 86% (p<0.0001). For endomyocardial-biopsy grades 1B or 2, a positive lymphocyte-growth assay alone was associated with high-grade rejection in 100% of cases.
Use of an algorithm combining three immunological factors at the time of a low-grade endomyocardial biopsy enables prospective stratification of cardiac transplant recipients into risk categories for progression to high-grade rejection. Low-risk individuals require fewer biopsies, moderate-risk individuals require an ongoing schedule of surveillance biopsies, and high-risk individuals require rational organisation of interventional strategies aimed at preventing rejection. Additional predictive factors are needed to identify moderate-risk individuals who will progress to rejection. Ultimately, successful intervention may have an impact on the subsequent complication of TCAD.
移植相关冠状动脉疾病（TCAD）在心脏移植受者中频繁发生，并限制了长期生存。我们研究了这种疾病与高级别排斥反应累积频率之间的关系，并调查了在低级别心内膜活检时同时使用三种免疫因素是否可以预测进展为高级别排斥反应。
我们通过Kaplan-Meier精算生命表研究了1992年至1996年间198例心脏移植受者中高级别排斥反应的累积年频率与TCAD之间的关系。在102例患者移植后的第一年中，收集了他们12个月内心内膜活检、淋巴细胞生长试验和抗HLA抗体测量的数据。我们通过卡方检验、Kaplan-Meier生存曲线和多变量逻辑回归分析计算了90天内高级别排斥反应的预测值。
我们发现排斥反应的累积年频率与TCAD发病之间存在直接相关性，每年排斥反应超过0.75次的患者风险最高（p=0.0002）。在低级别心内膜活检（0级或1A级）后，一个或多个供体-受体HLA-DR匹配可预防高级别排斥反应（p<0.001）。在有一个或两个DR匹配的个体中，淋巴细胞生长试验为阴性时，从低级别活检进展为高级别排斥反应的阴性预测值为87%。在没有DR匹配的个体中，淋巴细胞生长试验阳性或IgG抗主要组织相容性复合体（MHC）II类抗体的存在与进展为排斥反应的高概率独立相关（分别为64%和66%，p<0.0005）。当两种试验均为阳性且伴有低级别心内膜活检时，进展为高级别排斥反应的阳性预测值为86%（p<0.0001）。对于心内膜活检1B级或2级，仅淋巴细胞生长试验阳性在100%的病例中与高级别排斥反应相关。
在低级别心内膜活检时使用结合三种免疫因素的算法能够将心脏移植受者前瞻性地分层为进展为高级别排斥反应的风险类别。低风险个体需要较少的活检，中度风险个体需要持续进行监测活检，高风险个体需要合理组织旨在预防排斥反应的干预策略。需要额外的预测因素来识别将进展为排斥反应的中度风险个体。最终，成功的干预可能会对随后的TCAD并发症产生影响。
