The ability to identify specific HLA molecules against which a patient has alloantibodies has revolutionized assessment of immunologic compatibility. Anti-HLA antibodies are typically evaluated as reactive against well-defined serologic antigen groups. Thus, donor HLA genotyping is aimed at defining HLA at the serologic split-antigen level to avoid incompatible antigen-antibody combinations. However, anti-HLA antibodies can have reactivities not accurately described by well-defined serologic antigens. While existence of these antibodies is acknowledged, their precise impact on clinical practice is not clear. We performed a single-center review of 2 years of pre-and post-transplant anti-HLA antibody testing data combined with high-resolution HLA genotyping data for living and deceased organ donors to evaluate the clinical impact of anti-HLA antibodies with reactivities outside of commonly defined serologic antigen groups. We find approximately 15% of patients awaiting transplantation have alloantibodies with differential reactivity for HLA proteins encoded by specific alleles within a serologic antigen group. Allele-specific antibodies are associated with positive cellular crossmatches not accurately predicted by standard donor HLA genotyping and can manifest as post-transplant donor-specific antibodies. Our data highlights the importance of evaluating anti-HLA antibodies at the allele-level and provides evidence supporting utility for high-resolution HLA genotyping in solid organ transplantation.

鉴定患者具有同种抗体的特定HLA分子的能力彻底改变了免疫相容性评估。通常将抗HLA抗体评估为对明确的血清抗原组具有反应性。因此，供体HLA基因分型旨在在血清分裂抗原水平上定义HLA，以避免不相容的抗原-抗体组合。但是，抗HLA抗体的反应性不能由定义明确的血清学抗原准确描述。尽管已经确认这些抗体的存在，但它们对临床实践的确切影响尚不清楚。我们对移植前和移植后2年的抗HLA抗体测试数据与高分辨率的HLA基因分型数据进行了单中心回顾，以供活体和已故器官供体使用，以评估抗HLA抗体在体外具有反应性的临床影响通常定义的血清抗原组。我们发现约有15％的等待移植的患者具有同种抗体，这些同种抗体对血清抗原组内特定等位基因编码的HLA蛋白具有不同的反应性。等位基因特异性抗体与标准供体HLA基因分型无法准确预测的阳性细胞交叉匹配相关，并且可能表现为移植后供体特异性抗体。