Clinically relevant interpretation of solid phase assays for HLA antibody.
Clinically relevant interpretation of solid phase assays for HLA antibody.
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DOI：
10.1097/mot.0000000000000326
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发表时间：
2016-08
影响因子：
2.2
通讯作者：
Leffell MS
中科院分区：
文献类型：
--
作者：
Bettinotti MP;Zachary AA;Leffell MS
准确及时地检测和表征人类白细胞抗原（HLA）抗体对于移植前和移植后免疫风险评估至关重要。固相免疫测定提高了灵敏度和特异性，但测试解释并不总是简单明了。本次审查将考虑技术限制来讨论结果解释；评估相对抗体强度；以及整合来自补充测试和患者免疫史的风险分层数据。实验室和临床研究深入了解了测试失败的原因——由于针对变性 HLA 抗原的抗体而导致的假阳性反应，以及由于测试干扰和/或天然表位丢失而导致的假阴性反应。测试修改允许检测补体结合抗体并确定 IgG 亚类。单抗原固相免疫测定的高度特异性揭示了 HLA-C、HLA-DQ 和 HLA-DP 抗原抗体的复杂性和临床相关性。确定 HLA 表位的抗体特异性可以识别检测试剂盒中未包含的不相容抗原。通过固相免疫分析对 HLA 抗体进行检测和表征，加深了人们对这些抗体在移植物排斥中的作用的了解，改善了抗体介导的排斥反应的治疗，并增加了移植机会。然而，要实现这些好处，需要仔细、准确地解释测试结果。
Accurate and timely detection and characterization of human leukocyte antigen (HLA) antibodies are critical for pre-transplant and post-transplant immunological risk assessment. Solid phase immunoassays have provided increased sensitivity and specificity, but test interpretation is not always straightforward. This review will discuss the result interpretation considering technical limitations; assessment of relative antibody strength; and the integration of data for risk stratification from complementary testing and the patient's immunological history. Laboratory and clinical studies have provided insight into causes of test failures – false positive reactions because of antibodies to denatured HLA antigens and false negative reactions resulting from test interference and/or loss of native epitopes. Test modifications permit detection of complement-binding antibodies and determination of the IgG subclasses. The high degree of specificity of single antigen solid phase immunoassays has revealed the complexity and clinical relevance of antibodies to HLA-C, HLA-DQ, and HLA-DP antigens. Determination of antibody specificity for HLA epitopes enables identification of incompatible antigens not included in test kits. Detection and characterization of HLA antibodies with solid phase immunoassays has led to increased understanding of the role of those antibodies in graft rejection, improved treatment of antibody-mediated rejection, and increased opportunities for transplantation. However, realization of these benefits requires careful and accurate interpretation of test results.