Division of Abdominal Transplantation, Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, Texas, USA.
Department of Pathology, Division of Hepatic and Transplantation Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
Clin Transplant. 2024 Aug;38(8):e15434. doi: 10.1111/ctr.15434.
Uterus transplantation (UTx) is a novel treatment for absolute uterine infertility. Acute T cell-mediated rejection (TCMR) can be monitored only through serial cervical biopsies.
This study, the first of its kind in human transplantation, evaluated clinical, serological, and pathophysiological manifestations of allograft rejection from immunosuppression withdrawal (ISW) to graft hysterectomy (Hx).
Following live birth, immunosuppression was abruptly withdrawn from six living-donor UTx recipients. ISW occurred at a median of 7.4 weeks before graft Hx. Post-ISW signs of rejection included: (1) discoloration of the cervix; (2) increased uterine size compared to day of ISW; (3) serological evidence of eosinophilia and progressive development of donor-specific antibodies (DSA) or child-specific antibodies (CSA); (4) histopathological evidence of TCMR in cervical biopsies preceding the development of antibodies in serum; and (5) C4d deposition in tissue before formation of DSA or CSA in all but two recipients. At graft Hx, endometrial glands were preferentially targeted for destruction over stroma while parametrial arteries displayed variable arteritis and fibrointimal hyperplasia.
Recognition of the progression of uterine allograft rejection may be important for other human organ recipients and drive research on modulation of immunosuppression and the paradoxical relationship between adaptive cellular and humoral immunity in natural pregnancies.
ClinicalTrials.gov identifier: NCT02656550.
子宫移植（UTx）是一种治疗绝对子宫性不孕的新方法。急性 T 细胞介导的排斥反应（TCMR）只能通过连续的宫颈活检来监测。
本研究是人类移植领域的首例研究，评估了从免疫抑制停药（ISW）到移植子宫切除术（Hx）期间同种异体移植物排斥的临床、血清学和病理生理学表现。
在活产分娩后，六名活体供体 UTx 受者的免疫抑制剂被突然停药。ISW 发生在 Hx 前中位 7.4 周。ISW 后的排斥迹象包括：（1）宫颈变色；（2）与 ISW 当天相比，子宫大小增加；（3）血清学证据显示嗜酸性粒细胞增多和供体特异性抗体（DSA）或儿童特异性抗体（CSA）的逐渐发展；（4）在血清中抗体形成之前，宫颈活检中的 TCMR 组织病理学证据；（5）除两名受者外，所有受者的组织中 C4d 沉积先于 DSA 或 CSA 的形成。在 Hx 时，子宫内膜腺体优先受到破坏，而子宫旁动脉表现出不同程度的动脉炎和纤维内膜增生。
识别子宫同种异体移植物排斥的进展可能对其他人类器官受者很重要，并推动对免疫抑制的调节以及适应性细胞和体液免疫在自然妊娠中的矛盾关系的研究。
ClinicalTrials.gov 标识符：NCT02656550。
