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针对变性 HLA-A1 的供体特异性抗体:无临床意义?

Donor-specific antibody against denatured HLA-A1: clinically nonsignificant?

机构信息

Seattle Cancer Care Alliance, Clinical Research Division, Department of Laboratory Medicine, University of Washington, Seattle, Washington, USA.

出版信息

Hum Immunol. 2011 Jun;72(6):492-8. doi: 10.1016/j.humimm.2011.02.012. Epub 2011 Mar 9.

DOI:10.1016/j.humimm.2011.02.012
PMID:21396421
Abstract

Pre-transplant screening of a woman with end-stage renal disease (ESRD) showed no anti-human leukocyte antigen (HLA) alloantibodies by anti-human globulin-complement-dependent cytotoxicity (AHG-CDC; class I) or enzyme-linked immunosorbent assay (class II). Following a negative AHG-CDC crossmatch, an HLA01:01+ deceased donor (DD) kidney was transplanted in September 2005. Subsequent screening of pre-transplant serum by LABScreen Single Antigen (SA) array showed strong reactivity versus A01:01. Despite that reactivity, at 5 years post-transplant, the patient has a serum creatinine of 1.6 mg/dl and has never experienced humoral or cellular rejection. Retrospective flow-cytometric crossmatch of pre- and post-transplant sera versus DD cells was negative. Rescreening of multiple pre- and post-transplant sera revealed anti-A1 reactivity persisting from the first through the last samples tested. The patient's anti-A1 was almost two fold more reactive with denatured A*01:01 FlowPRA SA beads after denaturation with acid treatment (pH 2.7) than with untreated beads. Parallel results were observed with pH 2.7 treated versus untreated A1+ T cells in FXM. These data highlight the difficulty in interpreting screening results obtained using bead arrays, because of antibodies that appear to recognize denatured but not native class I HLA antigens. We suggest that such bead-positive, flow cytometric crossmatch negative antibodies are not associated with humoral rejection, may not necessarily be detrimental to a graft, and deserve further evaluation before becoming a barrier to transplantation.

摘要

一位终末期肾病(ESRD)女性患者在移植前的筛查中,抗人球蛋白-补体依赖性细胞毒性(AHG-CDC;I 类)或酶联免疫吸附试验(ELISA;II 类)均未显示出抗人类白细胞抗原(HLA)同种抗体。在 AHG-CDC 交叉配型阴性后,于 2005 年 9 月移植了 HLA01:01+的已故供体(DD)肾脏。随后通过 LABScreen 单抗原(SA)阵列对移植前血清进行的进一步筛查显示对 A01:01 具有强烈的反应性。尽管存在这种反应性,但在移植后 5 年,患者的血清肌酐为 1.6mg/dl,且从未经历过体液或细胞排斥反应。对供体和移植后血清进行回顾性流式细胞交叉配型与 DD 细胞均为阴性。对多个移植前和移植后血清的重新筛查显示,抗 A1 反应性从第一次测试到最后一次测试的样本均持续存在。经过酸处理(pH 2.7)使 A01:01 变性后,患者的抗 A1 与未处理的珠子相比,与变性的 A01:01 FlowPRA SA 珠子的反应性几乎增加了两倍。在 FXM 中,用 pH 2.7 处理的 A1+T 细胞与未经处理的细胞相比,也观察到了类似的结果。这些数据突出了使用珠子阵列获得的筛选结果解释的困难,因为这些抗体似乎识别变性但不识别天然的 I 类 HLA 抗原。我们建议,对于这些珠子阳性、流式细胞交叉配型阴性的抗体,不与体液排斥反应相关,可能不一定对移植物有害,并且在成为移植的障碍之前,值得进一步评估。

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