Department of Pathology, Baylor University Medical Center, Dallas, TX.
Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX.
Transplantation. 2022 Jan 1;106(1):167-177. doi: 10.1097/TP.0000000000003633.
Uterus transplantation (UTx) enables pregnancy in infertile women. This study describes the histopathological changes of ischemia reperfusion injury and mostly acute T-cell-mediated rejection (TCMR) in UTx and proposes modification toward a working formulation grading system with associated treatments.
Protocol and indication biopsies from 11 living and 2 deceased donor UTx recipients were analyzed. Serving as a control were 49 age-matched nontransplanted uteri. All posttransplant histopathological specimens were evaluated in a blinded fashion by 3 pathologists. Response to treatment was assessed by follow-up biopsies. Serial serum donor-specific antibody (DSA) responses were also recorded.
Changes attributed to ischemia reperfusion resolved within 2 wk of UTx in most of the patients. For TCMR grading, perivascular inflammation, focal capillary disruption, and interstitial hemorrhage were added to interface inflammation, intercellular edema, stromal inflammation, and epithelial apoptotic bodies. Of the 173 protocol biopsies, 98 were classified as negative for TCMR; 34 as indeterminate-borderline; 35 as mild; 3 as moderate; and 3 as severe, 1 of which occurred in a DSA-positive recipient and also showed microvascular injury. Corticosteroids successfully treated all moderate-to-severe TCMR episodes. Mild TCMR was treated by increasing existing baseline immunosuppression. Indeterminate-borderline episodes were not treated. Neither ischemia-reperfusion injury nor TCMR with DSA adversely affected embryo transfer.
Relying on a modified histopathological grading system, we developed a treatment strategy resulting in resolution of TCMR and successful pregnancies.
子宫移植（UTx）使不孕妇女能够怀孕。本研究描述了 UTx 中缺血再灌注损伤和主要急性 T 细胞介导的排斥反应（TCMR）的组织病理学变化，并提出了一种改良的工作方案分级系统及其相关治疗方法。
对 11 例活体和 2 例已故供体 UTx 受者的方案和适应证活检进行了分析。作为对照的是 49 例年龄匹配的未移植子宫。所有移植后组织病理学标本均由 3 位病理学家进行盲法评估。通过随访活检评估治疗反应。还记录了血清供体特异性抗体（DSA）的连续反应。
大多数患者的 UTx 后 2 周内，缺血再灌注引起的变化得到解决。对于 TCMR 分级，在血管周围炎症、局灶性毛细血管破坏和间质出血的基础上，增加了界面炎症、细胞间水肿、基质炎症和上皮凋亡小体。在 173 例方案活检中，98 例被归类为 TCMR 阴性；34 例为不确定-边界；35 例为轻度；3 例为中度；3 例为重度，其中 1 例发生在 DSA 阳性受者中，也显示微血管损伤。皮质类固醇成功治疗了所有中度至重度 TCMR 发作。轻度 TCMR 通过增加现有的基础免疫抑制来治疗。不确定-边界发作未治疗。无论是缺血再灌注损伤还是伴有 DSA 的 TCMR 均未影响胚胎移植。
基于改良的组织病理学分级系统，我们制定了一种治疗策略，成功解决了 TCMR 并实现了妊娠。
