背景:固相免疫测定(SPI)技术的引入,用于检测和表征移植中的人白细胞抗原(HLA)抗体,同时提供比补体依赖性淋巴细胞毒性(CDC)测定法更高的灵敏度。尽管在Luminex仪器上进行了SPI测定(以下称为Luminex测定),特别是,允许检测CDC检测不到的抗体,这些抗体的临床意义尚未完全了解。然而,这些抗体的检测导致致敏患者的临床管理发生变化。此外,SPI测试提出了在解释抗体结果时需要解决和仔细考虑的技术问题。
方法:在这种背景下,移植协会召集了一组移植领域的实验室和临床专家,以准备一份共识报告,并根据已发表的证据和专家意见就使用这项新技术提出建议。成立了三个工作组,以解决(a)与使用该技术有关的技术问题,(b)在各种临床环境和器官移植类型(肾脏,心,肺,肝脏,胰腺,肠,和胰岛细胞),和(c)抗体测试在移植后环境中的应用。这三个小组于2011年11月成立,并在罗马召开了“移植抗体共识会议”,意大利,2012年5月。三个小组分别然后一起开会的审议是本报告的基础。
结果:每组都准备了一份完整的建议清单。以下是主要建议的摘要。技术组:(a)SPI必须用于检测实体器官移植受者的移植前HLA抗体,特别是,使用单抗原珠测定法检测HLA基因座的抗体,例如Cw,DQA,DPA,DPB,不容易被其他方法检测到。(b)用于抗体检测的SPI的使用应补充基于细胞的测定,以检查两种类型的测定之间的相关性并建立正交叉匹配(XM)的可能性。(c)在使用Luminex磁珠技术时,必须了解可能影响结果及其临床解释的技术因素,例如抗原密度的变化和珠子上变性抗原的存在。移植前小组:(a)应根据抗体和获得的XM结果确定风险类别。(b)CDC检测到的DSA和阳性XM应避免,因为它们与抗体介导的排斥和移植物丢失密切相关。(c)如果针对所有I类和II类HLA基因座的抗体的单抗原珠筛选为阴性,则可以在没有预期XM的情况下进行肾移植。这个决定,然而,需要与当地临床项目和相关监管机构达成一致。(d)在心脏和肺移植中应避免存在DSAHLA抗体,并将其视为肝脏的危险因素,肠,胰岛细胞移植.移植后组:(a)高危患者(即,脱敏或DSA阳性/XM阴性)应在移植后的前3个月通过测量DSA和方案活检进行监测。(b)中危患者(DSA病史但目前阴性)应在第一个月内进行DSA监测。如果存在DSA,应该进行活检。(c)低风险患者(首次移植未致敏)应在移植后3至12个月至少进行一次DSA筛查。如果检测到DSA,应该进行活检。在所有三个类别中,后续治疗的建议基于活检结果.
结论:提供了完整的建议列表,涵盖了实体器官移植中HLA抗体的技术和移植前和移植后监测。这些建议旨在为与传统方法结合使用的最新开发的HLA抗体检测方法的使用和临床应用提供最新的指导。
BACKGROUND: The introduction of solid-phase immunoassay (SPI) technology for the detection and characterization of human leukocyte antigen (HLA) antibodies in transplantation while providing greater sensitivity than was obtainable by complement-dependent lymphocytotoxicity (CDC) assays has resulted in a new paradigm with respect to the interpretation of donor-specific antibodies (DSA). Although the SPI assay performed on the Luminex instrument (hereafter referred to as the Luminex assay), in particular, has permitted the detection of antibodies not detectable by CDC, the clinical significance of these antibodies is incompletely understood. Nevertheless, the detection of these antibodies has led to changes in the clinical management of sensitized patients. In addition, SPI testing raises technical issues that require resolution and careful consideration when interpreting antibody results.
METHODS: With this background, The Transplantation Society convened a group of laboratory and clinical experts in the field of transplantation to prepare a
consensus report and make recommendations on the use of this new technology based on both published evidence and expert opinion. Three working groups were formed to address (a) the technical issues with respect to the use of this technology, (b) the interpretation of pretransplantation antibody testing in the context of various clinical settings and organ transplant types (kidney, heart, lung, liver, pancreas, intestinal, and islet cells), and (c) the application of antibody testing in the posttransplantation setting. The three groups were established in November 2011 and convened for a \"
Consensus Conference on Antibodies in Transplantation\" in Rome, Italy, in May 2012. The deliberations of the three groups meeting independently and then together are the bases for this report.
RESULTS: A comprehensive list of recommendations was prepared by each group. A summary of the key recommendations follows. Technical Group: (a) SPI must be used for the detection of pretransplantation HLA antibodies in solid organ transplant recipients and, in particular, the use of the single-antigen bead assay to detect antibodies to HLA loci, such as Cw, DQA, DPA, and DPB, which are not readily detected by other methods. (b) The use of SPI for antibody detection should be supplemented with cell-based assays to examine the correlations between the two types of assays and to establish the likelihood of a positive crossmatch (XM). (c) There must be an awareness of the technical factors that can influence the results and their clinical interpretation when using the Luminex bead technology, such as variation in antigen density and the presence of denatured antigen on the beads. Pretransplantation Group: (a) Risk categories should be established based on the antibody and the XM results obtained. (b) DSA detected by CDC and a positive XM should be avoided due to their strong association with antibody-mediated rejection and graft loss. (c) A renal transplantation can be performed in the absence of a prospective XM if single-antigen bead screening for antibodies to all class I and II HLA loci is negative. This decision, however, needs to be taken in agreement with local clinical programs and the relevant regulatory bodies. (d) The presence of DSA HLA antibodies should be avoided in heart and lung transplantation and considered a risk factor for liver, intestinal, and islet cell transplantation. Posttransplantation Group: (a) High-risk patients (i.e., desensitized or DSA positive/XM negative) should be monitored by measurement of DSA and protocol biopsies in the first 3 months after transplantation. (b) Intermediate-risk patients (history of DSA but currently negative) should be monitored for DSA within the first month. If DSA is present, a biopsy should be performed. (c) Low-risk patients (nonsensitized first transplantation) should be screened for DSA at least once 3 to 12 months after transplantation. If DSA is detected, a biopsy should be performed. In all three categories, the recommendations for subsequent treatment are based on the biopsy results.
CONCLUSIONS: A comprehensive list of recommendations is provided covering the technical and pretransplantation and posttransplantation monitoring of HLA antibodies in solid organ transplantation. The recommendations are intended to provide state-of-the-art guidance in the use and clinical application of recently developed methods for HLA antibody detection when used in conjunction with traditional methods.