Diabetes Research Institute (DRI) and Clinical Cell Transplant Program, University of Miami Miller School of Medicine, Miami, FL.
Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL.
Transplantation. 2021 Nov 1;105(11):2490-2498. doi: 10.1097/TP.0000000000003635.
Allosensitization has been reported after discontinuation of immunosuppression following graft failure in islet transplantation (ITx) recipients, though duration of its persistence is unknown.
We evaluated 35 patients with type 1 diabetes who received ITx, including 17 who developed graft failure (ITx alone, n = 13; ITx plus bone marrow-derived hematopoietic stem cells, n = 4) and 18 with persistent graft function. Panel-reactive antibody (PRA) was measured yearly for the duration of graft function within 1 y after graft failure at enrollment and yearly thereafter.
In ITx alone graft failure patients, 61% (8/13) were PRA-positive at 6 y postgraft failure, and 46% (6/13) developed donor-specific anti-HLA antibodies (DSA to 2 ± 1 donors) during follow-up. The degree of sensitization was variable (cPRA ranging between 22% and 100% after graft failure). Allosensitization persisted for 7-15 y. Three subjects (3/13) were not allosensitized. In ITx plus bone marrow-derived hematopoietic stem cell recipients, cPRA-positivity (88%-98%) and DSA positivity persisted for 15 y in 75% (3/4) of subjects.
Allosensitization was minimal while subjects remained on immunosuppression, but after discontinuation of immunosuppressive therapy, the majority of subjects (77%) became allosensitized with persistence of PRA positivity for up to 15 y. Persistence of allosensitization in this patient population is of clinical importance as it may result in longer transplant waiting list times for identification of a suitable donor in the case of requiring a subsequent transplant.
胰岛移植（ITx）受者在移植物失功后停止免疫抑制时已报告发生同种致敏，但持续时间尚不清楚。
我们评估了 35 名接受 ITx 的 1 型糖尿病患者，包括 17 名发生移植物失功的患者（单纯 ITx，n=13；ITx 加骨髓源性造血干细胞，n=4）和 18 名持续有移植物功能的患者。在移植物失功后 1 年内每年评估 1 次 panel-reactive antibody（PRA），并在随后的每年评估 1 次。
在单纯 ITx 移植物失功患者中，61%（8/13）在移植物失功后 6 年时 PRA 阳性，46%（6/13）在随访期间发生供体特异性抗 HLA 抗体（针对 2±1 个供体的 DSA）。致敏程度不同（移植物失功后 cPRA 范围为 22%至 100%）。同种致敏持续 7-15 年。3 名患者（3/13）未发生同种致敏。在 ITx 加骨髓源性造血干细胞受者中，75%（3/4）的患者 cPRA 阳性（88%-98%）和 DSA 阳性持续 15 年。
在受者仍接受免疫抑制时，同种致敏程度最小，但在停止免疫抑制治疗后，大多数受者（77%）发生同种致敏，PRA 阳性持续长达 15 年。在这种患者人群中，同种致敏的持续存在具有重要的临床意义，因为在需要后续移植的情况下，它可能导致更长的移植等待时间，以确定合适的供体。
