Jaeger C, Brendel M D, Hering B J, Eckhard M, Bretzel R G
Third Medical Department and Policlinic, Justus-Liebig University, Giessen, Germany.
Diabetes. 1997 Nov;46(11):1907-10. doi: 10.2337/diab.46.11.1907.
Alloimmunity has been uncovered to be a cause of graft loss representing a major barrier for clinical islet transplantation, and several studies are designed to evaluate new strategies for immunosuppression to prevent alloimmunity. In contrast, the significance for autoimmune destruction of transplanted beta-cells has remained somewhat controversial. Recently, two case reports based on histological findings have suggested recurrent autoimmune insulitis despite immunosuppressive therapy both in clinical pancreas and in islet transplantation. In the present study, in 23 islet-grafted patients with IDDM receiving standard immunosuppressive therapy, we demonstrate that progressive impairment of islet graft function occurs significantly earlier in those individuals positive for autoantibodies as a typical stigma of diabetes-associated autoimmunity that is well established in the prediabetic periods of IDDM. Intraportal infusion of allogeneic islets was performed in 23 C-peptide-negative IDDM patients, according to the clinical transplantation categories defined as islet after kidney (IAK) or simultaneous islet and kidney (SIK). Complete islet graft failure was defined as the 1st day of permanent C-peptide negativity in the serum (<0.2 ng/ml) and C-peptide negativity in the urine (<2 microg/dl). The median observation period following islet transplantation was 12 months (range 1-50) with a cumulative follow-up of 336 months. Islet cell antibodies (ICAs) and GAD65 antibodies were monitored before and regularly after islet transplantation. Kaplan-Meier survival analysis and log-rank statistics revealed a significant (P < 0.05) difference in cumulative islet graft survival depending on the presence of islet cell and/or GAD65 antibodies. These results strongly suggest that recurrent autoimmunity directed to transplanted beta-cells contributes to islet graft failure despite sustained immunosuppression. For successful clinical islet transplantation in the future, new immunosuppressive therapies are needed to prevent both alloimmunity and autoimmunity.
同种免疫已被发现是移植物丢失的一个原因，这是临床胰岛移植的一个主要障碍，并且有几项研究旨在评估预防同种免疫的新免疫抑制策略。相比之下，移植β细胞自身免疫性破坏的重要性仍存在一定争议。最近，两项基于组织学发现的病例报告表明，在临床胰腺移植和胰岛移植中，尽管进行了免疫抑制治疗，但仍有复发性自身免疫性胰岛炎。在本研究中，我们对23例接受标准免疫抑制治疗的胰岛移植IDDM患者进行了研究，结果表明，对于那些自身抗体呈阳性的个体，胰岛移植功能的进行性损害显著更早出现，自身抗体是糖尿病相关自身免疫的典型标志，在IDDM的糖尿病前期就已确立。根据临床移植类别，即肾后胰岛移植（IAK）或胰岛与肾同时移植（SIK），对23例C肽阴性的IDDM患者进行了门静脉内同种异体胰岛输注。完全胰岛移植失败定义为血清中永久性C肽阴性（<0.2 ng/ml）和尿中C肽阴性（<2 μg/dl）的第1天。胰岛移植后的中位观察期为12个月（范围1 - 50个月），累计随访336个月。在胰岛移植前后定期监测胰岛细胞抗体（ICA）和GAD65抗体。Kaplan-Meier生存分析和对数秩统计显示，根据胰岛细胞和/或GAD65抗体的存在情况，累积胰岛移植存活率存在显著差异（P < 0.05）。这些结果强烈表明，尽管持续进行免疫抑制，但针对移植β细胞的复发性自身免疫仍会导致胰岛移植失败。为了未来临床胰岛移植的成功，需要新的免疫抑制疗法来预防同种免疫和自身免疫。
