Maxfield S J, Taylor C J, Kosmoliaptsis V, Broecker V, Watson C J E, Bradley J A, Peacock S
Histocompatibility and Immunogenetics Laboratory, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
Department of Surgery, University of Cambridge and NIHR Cambridge Biomedical Research Centre, Cambridge, UK.
Am J Transplant. 2015 Sep;15(9):2501-6. doi: 10.1111/ajt.13300. Epub 2015 May 1.
We report for the first time the adoptive transfer of donor HLA-specific allosensitization in two recipients following kidney transplantation from a highly sensitized donor. Kidneys from a donation after circulatory death donor were transplanted into two nontransfused, HLA-specific antibody negative males receiving their first transplant. Antibody screening 7 days after transplant showed high level de novo IgG HLA class I- and class II-specific antibodies in both recipients, with largely overlapping antibody profiles but no antibodies to donor HLA. The unusually rapid appearance of de novo alloantibodies in immunosuppressed nonsensitized recipients and absence of donor HLA-specific antibody prompted testing of stored donor serum that revealed high antibody levels with specificities very similar to those seen in both recipients, but in addition the presence of strong antibodies to each recipient HLA. Alloantibody levels gradually declined but were still detectable at 3 months. These findings suggest that alloreactive passenger B cells/plasma cells within the kidneys of highly sensitized donors may give rise to rapid development of posttransplant de novo HLA-specific alloantibodies. While the clinical significance of this phenomenon is uncertain it provides one explanation for the appearance of de novo HLA-specific antibodies directed against third party but not donor HLA.
我们首次报告了在接受来自高敏供体的肾移植后,两名受者出现供体HLA特异性同种致敏的过继转移情况。来自循环死亡后供体的肾脏被移植到两名首次接受移植的未输血、HLA特异性抗体阴性男性受者体内。移植后7天的抗体筛查显示,两名受者体内均出现了高水平的新生IgG HLA I类和II类特异性抗体,抗体谱在很大程度上重叠,但没有针对供体HLA的抗体。免疫抑制的未致敏受者中异常迅速出现的新生同种抗体以及供体HLA特异性抗体的缺失,促使对储存的供体血清进行检测,结果显示抗体水平很高,其特异性与两名受者体内所见的非常相似,但此外还存在针对每个受者HLA的强抗体。同种抗体水平逐渐下降,但在3个月时仍可检测到。这些发现表明,高敏供体肾脏内的同种反应性过客B细胞/浆细胞可能导致移植后新生HLA特异性同种抗体的快速产生。虽然这一现象的临床意义尚不确定,但它为针对第三方而非供体HLA的新生HLA特异性抗体的出现提供了一种解释。