Use of short tandem repeats for DNA fingerprinting to rapidly diagnose graft-versus-host disease in solid organ transplant patients
Use of short tandem repeats for DNA fingerprinting to rapidly diagnose graft-versus-host disease in solid organ transplant patients
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DOI：
10.1097/01.tp.0000190431.94252.3f
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发表时间：
2006-01-15
期刊：
影响因子：
6.2
通讯作者：
Gorden, DL
中科院分区：
文献类型：
--
作者：
Schrager, JJ;Vnencak-Jones, CL;Gorden, DL
背景。移植物抗宿主病（GVHD）是肝移植后罕见的并发症，预后较差，死亡率接近90-95%。GVHD的诊断往往被延迟，因为早期症状模仿更常见的实体，如药物反应和病毒综合征。迄今为止，明确的诊断一直很困难，并依赖于临床和组织病理学变量的星座。我们提出使用短串联重复DNA“指纹”技术作为肝移植后GVHD患者早期，明确诊断的方法。一例尸体肝移植患者，移植后无并发症，移植后4周出现发热、腹泻、手掌、脚底和背部黄斑丘疹。尽管对感染性病因进行了经验性治疗，但患者的病情仍在恶化。皮肤和直肠活检可疑gvhd。从皮肤和直肠活检以及供体淋巴结中分离出DNA。对每个标本的9个高度多态性短串联重复序列进行PCR扩增，并从中获得独特的DNA“指纹”。来自皮肤和直肠的DNA显示出与供体和受体等位基因的混合嵌合。彻底的分析证实了gvhd。短串联重复DNA指纹图谱是肝移植后GVHD明确诊断的一种有效且可重复的方法。使用该技术快速检测GVHD，再加上早期开始治疗，可能会提高GVHD患者在实体器官移植后的生存率。
Background. Graft-versus-host disease (GVHD) is a rare complication following liver transplantation and carries a poor prognosis with mortality approaching 90-95%. Diagnosis of GVHD is often delayed due to early symptoms mimicking more common, entities such as drug reactions and viral syndromes. To date, definitive diagnosis has been difficult and has relied on a constellation of clinical and histopathologic variables. We present the use of short tandem repeat DNA "fingerprinting" technology as a method of early, definitive diagnosis of GVHD in patients after liver transplantation.Methods. A patient status-postorthotopic cadaveric-liver transplant, with an uncomplicated immediate posttransplant course, presented 4 weeks after transplant with fever, diarrhea, and maculopapular rash on her palms, soles, and back. The patient's condition worsened despite empiric treatment for an infectious etiology. Skin and rectal biopsies were suspicious for GVHD.Results. DNA was isolated from the skin and rectal biopsies as well as from a donor lymph node. PCR amplification was done for nine highly polymorphic short tandem repeats for each specimen and a unique DNA "fingerprint" was obtained from each. DNA from skin and rectum demonstrated mixed chimerism with both donor and recipient alleles detected. Thorough analysis confirmed GVHD.Conclusion. Short tandem repeats for DNA Fingerprinting represents an efficient and reproducible method for the definitive diagnosis of GVHD after liver transplantation. Rapid detection of GVHD using this technology, coupled with early initiation of therapy, may lead to improved Survival for patients with GVHD after solid organ transplant.