Preformed antibodies detected by cytotoxic assay or multibead array decrease liver allograft survival: Role of human leukocyte antigen compatibility

Preformed antibodies detected by cytotoxic assay or multibead array decrease liver allograft survival: Role of human leukocyte antigen compatibility
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DOI:
10.1002/lt.21408
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发表时间:
2008-04-01
影响因子:
4.6
通讯作者:
Paz-Artal, Estela
Paz-Artal, Estela
中科院分区:
医学2区
文献类型:
--
作者:
Castillo-Rama, Marcela;Castro, Maria Jose;Paz-Artal, Estela

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人类白细胞抗原(HLA)相容性和预存抗体在肝移植中的意义尚不清楚。本研究的目的是在一个包含896例肝移植的单中心队列中评价供受体相容性和预先形成的抗体是否改变了移植物存活率。单变量Kaplan-Meier分析表明,供受者HLA相容性对同种异体移植物存活率的影响很小。就单个抗原位点的相容性而言,HLA-A的2个错配在再次移植的同种异体移植物中赋予了存活优势(P = 0.011)。HLA-B和HLA-DR基因座在任何病理学结果中均不起显著作用。通过补体依赖性细胞毒性(CDC)和多珠测定(Luminex((R))xMAP)检测的预先形成的抗体的结果的一致性显示两种技术之间的强相关性(P < 0.0001)。CDC检测和Luminex检测的抗体均与移植后第一年内移植物存活率较短相关(分别为P = 0.01和P = 0.016)。阳性CDC T交叉配型和Luminex检测的HLA II类抗体在降低移植物存活率方面发挥了重要作用(1年时分别为P = 0.043和P = 0.0019,5年时分别为P = 0.005和P = 0.038)。还观察到预先形成的Luminex检测的II类或Luminex I和II抗体的存在与同种异体移植排斥反应之间的相关性(分别为P = 0.001和P = 0.042)。总之,尽管HLA分型不是移植的先决条件,但使用Luminex技术和CDC交叉配型筛查HLA抗体可能有助于检测高危患者,这些患者可能受益于移植后增加的监测和定制治疗。
The significance of human leukocyte antigen (HLA) compatibility and preformed antibodies in liver transplantation remains unclear. The objectives of this study were to evaluate, in a single-center cohort comprising 896 liver transplants, whether the degree of donor-recipient compatibility and preformed antibodies modified graft survival. Univariate Kaplan-Meier analysis demonstrated that donor-recipient HLA compatibility had a marginal impact on allograft survival. As for compatibility at individual antigen loci, 2 mismatches at HLA-A conferred a survival advantage in retransplanted allografts (P = 0.011). HLA-B and HLA-DR loci did not play a significant role in outcome in any pathology. The concordance of results on preformed antibodies detected by complement-dependent cytotoxicity (CDC) and a multiple bead assay (Luminex((R)) xMAP) showed a strong correlation between both techniques (P < 0.0001). Both CDC-detected and Luminex-detected antibodies were associated with shorter graft survival within the first year post-transplant (P = 0.01 and P = 0.016, respectively). Positive CDC T crossmatches and Luminex-detected HLA class II antibodies played a significant role in decreasing graft survival (P = 0.043 and P = 0.0019 at 1 year, respectively, and P = 0.005 and P = 0.038 at 5 years, respectively). A correlation was also observed between the presence of preformed Luminex-detected class II or Luminex I and II antibodies and allograft rejection (P = 0.001 and P = 0.042, respectively). In conclusion, although HLA typing is not a prerequisite for transplantation, screening of HLA antibodies with Luminex techniques and CDC crossmatch may be useful in the detection of at-risk patients that could benefit from increased surveillance and tailored therapy following transplantation.