Monitoring systemic donor lymphocyte macrochimerism to aid the diagnosis of graft-versus-host disease after liver transplantation
Monitoring systemic donor lymphocyte macrochimerism to aid the diagnosis of graft-versus-host disease after liver transplantation
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DOI：
10.1097/01.tp.0000103721.29729.fe
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发表时间：
2004-02-15
期刊：
影响因子：
6.2
通讯作者：
Taylor, CJ
中科院分区：
文献类型：
--
作者：
Taylor, AL;Gibbs, P;Taylor, CJ
背景。肝移植后移植物抗宿主病（GvHD）的诊断可能很困难，因为早期症状通常是非特异性的。在这项研究中，检查了受者外周血中供体淋巴细胞大嵌合的存在，作为尸体供体肝移植后 GvHD 的诊断辅助手段。方法。 1996 年至 2002 年间，对 33 名临床怀疑患有 GvHD（皮疹、腹泻、发热、全血细胞减少或贫血，无明显其他原因）的肝移植受者进行了外周血供体淋巴细胞大嵌合现象的调查。在首次临床表现时，通过低灵敏度聚合酶链式反应 (PCR) 确定供体大嵌合状态，以使用从受体外周血中提取的基因组 DNA 检测供体人类白细胞抗原 (HILA) 等位基因。当检测到供体 HLA 等位基因时，使用针对不匹配的供体和受体 HLA 等位基因的特异性抗体，通过双色流式细胞术分析来量化供体 T 细胞的百分比。检查供体淋巴细胞大嵌合现象的存在或不存在与基于临床和组织学标准的最终诊断之间的关系。结果。 33 名患者中有 7 名供体 HLA 等位基因 PCR 呈阳性。所有患者均存在大嵌合现象，供体 T 淋巴细胞水平占循环淋巴细胞的 4% 至 50%。所有七名患者的肝功能检查均正常，没有皮疹，并通过皮肤或肠道活检进行组织学证实的 GvHD 诊断。 26 名患者的 PCR 呈阴性，其中 23 名患者最终得到了替代诊断。其余三名患者迅速自发康复，没有进一步提示 GvHD 的症状。结论。供体淋巴细胞大嵌合。存在于所有确诊 GvHD 的患者中。对于症状符合 GvHD 且供体 HLA 的 PCR 呈阴性的患者，最终会建立替代诊断或患者会自行康复。通过 PCR 检测受者外周血中供者 HILA 等位基因是肝移植后 GvHD 的有用诊断工具。
Background. The diagnosis of graft-versus-host disease (GvHD) after liver transplantation can be difficult because early symptoms are often nonspecific. In this study, the presence of donor lymphocyte macrochimerism in recipient peripheral blood was examined as a diagnostic aid for GvHD after cadaveric donor liver transplantation.Methods. Between 1996 and 2002, 33 liver transplant recipients with a clinical suspicion of GvHD (skin rash, diarrhea, pyrexia, pancytopenia, or anemia, without an obvious alternative cause) were investigated for peripheral blood donor lymphocyte macrochimerism. Donor macrochimerism was determined at the time of first clinical presentation by a low-sensitivity polymerase chain reaction (PCR) to detect donor human leukocyte antigen (HILA) alleles using genomic DNA extracted from recipient peripheral blood. Where donor HLA alleles were detected, the percentage of donor T cells was quantified by two-color flow cytometric analysis using antibodies specific for mismatched donor and recipient HLA alleles. The relationship between the presence or absence of donor lymphocyte macrochimerism and final diagnoses based on clinical and histological criteria was examined.Results. Seven of the 33 patients were PCR positive for donor HLA alleles. All had macrochimerism, with donor T lymphocyte levels ranging from 4% to 50% of circulating lymphocytes. All seven patients had normal liver function tests, skin rash, and diagnosis of GvHD histologically confirmed by skin or gut biopsies. Twenty-six patients were PCR negative, and, in 23, an alternative diagnosis was eventually established. The remaining three patients made a rapid and spontaneous recovery with no further symptoms suggestive of GvHD.Conclusions. Donor lymphocyte macrochimerism. was present in all patients in whom the diagnosis of GvHD was confirmed. In patients with symptoms consistent with GvHD and a negative PCR for donor HLA, an alternative diagnosis was eventually established or the patients recovered spontaneously. Detection of donor HILA alleles in recipient peripheral blood by PCR is a useful diagnostic tool for GvHD after liver transplantation.