Montagna D, Maccario R, Comoli P, Prete L, Zecca M, Giraldi E, Daielli C, Moretta A, De Stefano P, Locatelli F
Department of Pediatrics, University of Pavia, IRCCS Policlinico, San Matteo, Italy.
J Clin Immunol. 1996 Mar;16(2):107-14. doi: 10.1007/BF01540957.
Bone marrow transplantation (BMT) from unrelated volunteers is frequently associated with both increased incidence and increased severity of acute graft-versus-host disease (GVHD). In the last years, it has been suggested that the analysis of the frequency of cytotoxic T lymphocyte precursors (CTLp) of unrelated HLA-matched donors can be used to detect disparity for HLA class I antigens and as a predictive test for development of severe GVHD. In this report, we summarized our experience regarding 20 pediatric patients affected by various hematological disorders, receiving allogeneic BMT from unrelated donors. HLA class I and II antigens of donor/recipient pairs were determined by means of serological typing, whereas molecular typing of HLA-class II antigens of patients and their potential donors was performed using PCR-SSP and PCR-fingerprinting techniques. CTLp values, estimated using limiting dilution analysis, were high (range, 1:7000-1:40,000) in 9 of 20 patients, while the other 11 children had low or undetectable levels (< 1:100,000) of CTL precursors. CTLp frequency was compared with the incidence and severity of GVHD observed after BMT. Our data demonstrate that the frequency of donor CTLp does not statistically correlate either with the occurrence of clinically significant acute GVHD or with disparity for HLA-class II molecular typing between donor and recipient. In particular, 4 of the 10 evaluable patients with an undetectable CTLp frequency developed grade IV, III, II, and IV acute GVHD, respectively. Although the limited number of subjects studied does not allow us to draw any firm conclusion, our data suggest a certain caution in considering this test suitable for the selection of potential donors.
来自无关志愿者的骨髓移植(BMT)常常伴随着急性移植物抗宿主病(GVHD)发病率的增加和严重程度的加重。在过去几年中,有人提出分析无关的HLA匹配供者的细胞毒性T淋巴细胞前体(CTLp)频率可用于检测HLA I类抗原的差异,并作为严重GVHD发生的预测性检测。在本报告中,我们总结了20例患有各种血液系统疾病的儿科患者接受无关供者异基因BMT的经验。供者/受者对的HLA I类和II类抗原通过血清学分型确定,而患者及其潜在供者的HLA II类抗原的分子分型则使用PCR-SSP和PCR指纹技术进行。使用极限稀释分析估计的CTLp值在20例患者中的9例中较高(范围为1:7000 - 1:40000),而其他11名儿童的CTL前体水平较低或无法检测到(<1:100000)。将CTLp频率与BMT后观察到的GVHD的发病率和严重程度进行了比较。我们的数据表明,供者CTLp的频率与临床上显著的急性GVHD的发生或供者与受者之间HLA II类分子分型的差异在统计学上均无相关性。特别是,10例可评估的CTLp频率无法检测到的患者中有4例分别发生了IV级、III级、II级和IV级急性GVHD。虽然研究对象数量有限,不允许我们得出任何确凿的结论,但我们的数据表明在认为该检测适用于潜在供者的选择时应有所谨慎。