Brown Audrey E, Kelly Yvonne M, Zarinsefat Arya, Meier Raphael P H, Worner Giulia, Tavakol Mehdi, Sarwal Minnie M, Laszik Zoltan G, Stock Peter G, Sigdel Tara K
Department of Surgery, University of California, San Francisco, California, USA.
Department of Surgery, University of California, San Francisco, California, USA; Department of Surgery, Columbia University, New York, New York, USA.
Am J Transplant. 2025 Feb;25(2):316-328. doi: 10.1016/j.ajt.2024.09.032. Epub 2024 Sep 28.
Pancreas transplantation improves glycemic control and mortality in patients with diabetes but requires aggressive immunosuppression to control the alloimmune and autoimmune response. Recent developments in "omics" methods have provided gene transcript-based biomarkers for organ transplant rejection. The tissue Common Response Module (tCRM) score is developed to identify the severity of rejection in kidney, heart, liver, and lung transplants. Still, it has not yet been validated in pancreas transplants (PT). We evaluated the tCRM score's relevance in PT and additional markers of acute cellular rejection (ACR) for PT. An analysis of 51 pancreas biopsies with ACR identified 37 genes and 56 genes significantly upregulated in the case of grade 3 and grade 2 ACR, respectively (P < .05). Significant differences were seen with higher grades of rejection among several transcripts. Of the 22 genes differentially expressed in grade 3 ACR, 18 were also differentially expressed in grade 2 ACR. The rejection signal was attributable to activated leukocytes' infiltration. Significantly higher tCRM scores were found in grade 3 ACR (P = .007) and grade 2 ACR (P = .004), compared to normal samples. The tCRM score was able to distinguish treatment-resistant cases from those successfully treated for rejection.
胰腺移植可改善糖尿病患者的血糖控制并降低死亡率，但需要积极的免疫抑制来控制同种免疫和自身免疫反应。“组学”方法的最新进展为器官移植排斥反应提供了基于基因转录本的生物标志物。组织共同反应模块（tCRM）评分用于识别肾、心、肝和肺移植排斥反应的严重程度。然而，它尚未在胰腺移植（PT）中得到验证。我们评估了tCRM评分在PT中的相关性以及PT急性细胞排斥反应（ACR）的其他标志物。对51例发生ACR的胰腺活检组织进行分析，结果显示，在3级和2级ACR病例中，分别有37个基因和56个基因显著上调（P <.05）。在几个转录本中，较高等级的排斥反应存在显著差异。在3级ACR中差异表达的22个基因中，有18个在2级ACR中也有差异表达。排斥信号归因于活化白细胞的浸润。与正常样本相比，3级ACR（P =.007）和2级ACR（P =.004）的tCRM评分显著更高。tCRM评分能够区分抗治疗的病例和成功治疗排斥反应的病例。
