Kimball P, Ham J, Eisenberg M, King A, Fisher R, Rhodes C, Posner M
Department of Surgery, Medical College of Virginia, Richmond 23898, USA.
Transplantation. 1997 Jun 15;63(11):1685-8. doi: 10.1097/00007890-199706150-00025.
This case report is the first documentation of the occurrence and potential source of lethal graft-versus-host disease (GVHD) after simultaneous kidney-pancreas transplantation. The patient was a 27-year-old African-American male who received an ABO-compatible, five HLA antigen-mismatched kidney-pancreas transplant from a 17-year-old African-American female donor, who died after childbirth.
Preoperative crossmatches using lymphocytotoxicity and flow cytometry were negative. The patient received four blood transfusions within 10 days of transplantation. Immunosuppression consisted of OKT3 induction, and then cyclosporine, azathioprine, and corticosteroids.
On postoperative day (POD) 9, the patient became febrile, and leukocytopenia and pancytopenia developed. Immunosuppression was reduced and granulocyte colony-stimulating factor was begun. Cultures were negative, interleukin 6 and interleukin 8 levels were elevated, and a cutaneous rash appeared on POD 18. A skin biopsy demonstrated dermatitis with focal epidermal necrosis consistent with GVHD. In an attempt to identify the source of GVHD, variable-number tandem repeat analysis fingerprinting was performed with DNA from donor splenocytes, from the skin biopsy, as well as from the patient's buccal mucosa. The skin biopsy showed a mixed variable-number tandem repeat analysis type containing DNA fragments matching the recipient and donor. Blood donors were excluded as a source because they were serologically different from the organ donor. The patient developed liver abnormalities and died from multiorgan failure on POD 22.
We speculate that carryover of passenger donor lymphocytes within the transplanted organ were responsible for GVHD. Furthermore, donor traits such as sexual mismatching, African-American race, and alloimmune status may be important potential risk factors for GVHD.
本病例报告首次记录了同时进行肾胰腺移植后发生致命性移植物抗宿主病（GVHD）的情况及其潜在来源。患者为一名27岁的非裔美国男性，接受了来自一名17岁非裔美国女性供体的ABO血型相容、HLA五个抗原位点不匹配的肾胰腺移植，该供体产后死亡。
术前采用淋巴细胞毒性试验和流式细胞术进行交叉配型均为阴性。患者在移植后10天内接受了4次输血。免疫抑制方案包括OKT3诱导，随后使用环孢素、硫唑嘌呤和皮质类固醇。
术后第9天，患者发热，出现白细胞减少和全血细胞减少。免疫抑制药物减量并开始使用粒细胞集落刺激因子。培养结果为阴性，白细胞介素6和白细胞介素8水平升高，术后第18天出现皮疹。皮肤活检显示为皮炎伴局灶性表皮坏死，符合GVHD表现。为确定GVHD的来源，对供体脾细胞、皮肤活检组织以及患者口腔黏膜的DNA进行了可变数目串联重复序列分析指纹图谱检测。皮肤活检显示为混合的可变数目串联重复序列分析类型，含有与受体和供体匹配的DNA片段。排除献血者作为来源，因为他们与器官供体血清学不同。患者出现肝脏异常，于术后第22天死于多器官功能衰竭。
我们推测移植器官内残留的供体过客淋巴细胞是导致GVHD的原因。此外，供体特征如性别不匹配、非裔美国人种族和同种免疫状态可能是GVHD重要的潜在危险因素。
