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供者HLA分型信息缺失移植受者DSA判定2例并文献复习

Recipient DSA determination when donor HLA typing information is unavailable: a report of two cases and literature review

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【作者】 黄铭理王於尘严紫嫣方翊灵刘燕娜耿舰邓文锋肖露露徐健苗芸

【Author】 Huang Mingli;Wang Yuchen;Yan Ziyan;Fang Yiling;Liu Yanna;Geng Jian;Deng Wenfeng;Xiao Lulu;Xu Jian;Miao Yun;Department of Transplantation, Nanfang Hospital, Southern Medical University;Department of Microbiology and Infectious Disease Center,School of Basic Medical Sciences,Peking University Health Science Center;Department of Pathology, Nanfang Hospital, Southern Medical University;

【通讯作者】 苗芸;

【机构】 南方医科大学南方医院器官移植科北京大学医学部基础医学院病原生物学系南方医科大学南方医院病理科

【摘要】 目的 为供者人类白细胞抗原(human leukocyte antigen,HLA)分型信息缺失并可疑抗体介导排斥反应(antibody-mediated rejection,AMR)的临床情景提供供者特异性抗体(donor-specific antibody,DSA)判读的方法,提高临床诊疗的准确性。方法 获取2例可疑AMR患者的新鲜移植肾组织,一部分经消化、提取总DNA后进行供受者HLA分型,将总HLA分型信息与受者外周血HLA分型信息对比,获得供者HLA分型信息。另一部分移植肾组织制作石蜡块,行HE染色、C4d免疫组化等常规病理镜检。结合患者临床表现、病理镜检结果、受者外周血HLA抗体检测结果、供受者HLA分型信息,判断患者是否为DSA介导AMR。结果 第1例患者拟诊为DSA介导的C4d(-)AMR,予移植肾切除后恢复透析;第2例患者不属于DSA介导的AMR,予甲泼尼龙冲击治疗3 d后病情好转,目前患者生存情况和移植肾功能良好。结论 在供者HLA分型信息缺失情况下,利用移植肾活检组织对供者进行HLA分型从而判定DSA存在的方法为跨地域、跨医疗中心就医的移植肾受者随诊工作提供必要的技术支持。对于可疑AMR患者,应当结合供受者HLA分型、DSA判读与病理镜检结果,以作出准确的临床诊断,指导患者的精准治疗。

【Abstract】 Objective A method for interpretation of donor-specific antibody(DSA) when the donor human leukocyte antigen(HLA) typing information is unavailable but with suspected antibody-mediated rejection(AMR) was demonstrated, which may improve the accuracy of clinical diagnosis and treatment. Methods Fresh transplanted kidney tissues from two patients with suspected AMR were obtained and digested for total DNA extraction. Then HLA typings of the donor and recipient was conducted. The donor HLA typing was obtained by matching the total HLA typing information with the recipient peripheral blood HLA typing. HE staining and C4 d immunohistochemistry staining of the paraffin-embedded tissues of the transplanted kidney were performed. DSA-mediated AMR was determined based on the patient’s clinical manifestations, pathological findings, recipient’s peripheral blood HLA antibody test and HLA typing results of the donor and recipient. Results One case was diagnosed with DSA-mediated C4 d-negative AMR and returned to dialysis after graft nephrectomy while the other case was not considered having DSA-mediated AMR. The patient’s condition improved after 3 d of high-dose prednisolone therapy. The patient was currently surviving with a well-functioning transplanted kidney. Conclusion The method of identifying DSA by the donor HLA typing results using the transplanted kidney biopsy tissues provides necessary technical support for the follow-up of kidney transplant recipients who seek care at different medical centers with unavailable donor HLA typing information. In patients with suspected AMR, HLA typing of donor and recipient, DSA interpretation, and pathological findings should be combined to make an accurate clinical diagnosis and to guide the precise treatment.

【基金】 国家自然科学基金(82070770);广东省自然科学基金(2020A1515010674);广州市科技计划项目(201803010109);南方医院院长基金(2018B009,2018C003);大学生创新创业训练计划项目(202012121046,X202012121239)
  • 【文献出处】 实用器官移植电子杂志 ,Practical Journal of Organ Transplantation(Electronic Version) , 编辑部邮箱 ,2022年03期
  • 【分类号】R699.2
  • 【下载频次】47
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