De Novo Donor-Specific HLA Antibodies Are Associated With Rapid Loss of Graft Function Following Islet Transplantation in Type 1 Diabetes
De Novo Donor-Specific HLA Antibodies Are Associated With Rapid Loss of Graft Function Following Islet Transplantation in Type 1 Diabetes
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DOI：
10.1111/ajt.13407
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发表时间：
2015-12-01
影响因子：
8.8
通讯作者：
Shaw, J. A. M.
中科院分区：
文献类型：
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作者：
Brooks, A. M. S.;Carter, V.;Shaw, J. A. M.
胰岛移植后的预后继续改善，但移植失败的病因尚不清楚。移植后新生供体特异性人白细胞抗原（HLA）抗体（DSA）越来越被认为是一个阴性预后标志物。DSA与移植物功能之间的具体时间关联仍然不明确，特别是在进行多次顺序移植的项目中。在单中心连续接受他克莫司/霉酚酸酯免疫抑制的患者中，前瞻性地测定了首次胰岛移植后12个月内从头DSA对移植物功能的影响。在移植前和移植后1-3个月进行混合膳食耐受性试验和HLA抗体评估。16名参与者总共接受了26次胰岛移植。5例（19%）移植物伴有新生DSA。5名（31%）受者受到影响：3名首次移植后受者；两次秒后移植。所有致敏性移植物在4周内发生DSA，并与移植后3个月刺激c肽减少（中位数[四分位数范围]）相关(DSA阴性：613(300-1090)；DSA阳性106(34-235)pmol/L [p=0.004]。尽管在没有进行非致敏性移植的情况下，在12个月的免疫抑制维持中，针对最近的胰岛移植的新DSA与移植物功能丧失绝对相关。阿仑妥珠单抗诱导免疫抑制与新生DSA形成发生率降低相关（p=0.03）。
Outcomes after islet transplantation continue to improve but etiology of graft failure remains unclear. De novo donor-specific human leukocyte antigen (HLA) antibodies (DSA) posttransplant are increasingly recognized as a negative prognostic marker. Specific temporal associations between DSA and graft function remain undefined particularly in programs undertaking multiple sequential transplants. Impact of de novo DSA on graft function over 12 months following first islet transplant was determined prospectively in consecutive recipients taking tacrolimus/mycophenolate immunosuppression at a single center. Mixed-meal tolerance test was undertaken in parallel with HLA antibody assessment pretransplant and 1-3 months posttransplant. Sixteen participants received a total of 26 islet transplants. Five (19%) grafts were associated with de novo DSA. Five (31%) recipients were affected: three post-first transplant; two post-second transplant. DSA developed within 4 weeks of all sensitizing grafts and were associated with decreased stimulated C-peptide (median [interquartile range]) at 3 months posttransplant (DSA negative: 613(300-1090); DSA positive 106(34-235) pmol/L [p=0.004]). De novo DSA directed against most recent islet transplant were absolutely associated with loss of graft function despite maintained immunosuppression at 12 months in the absence of a rescue nonsensitizing transplant. Alemtuzumab induction immunosuppression was associated with reduced incidence of de novo DSA formation (p=0.03).