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.

中文翻译：

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基于基因表达的胰腺移植排斥反应分子评分，用于定量评估排斥反应的严重程度和对治疗的抵抗力


胰腺移植可改善糖尿病患者的血糖控制和死亡率，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”方法的最新发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） 评分用于确定肾脏、心脏、肝脏和肺移植中排斥反应的严重程度。尽管如此，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。用 ACR 对 51 例胰腺活检的分析确定了 37 个基因和 56 个基因分别在 3 级和 2 级 ACR 的情况下显著上调 （P < .05）。在几个转录本中，较高的排斥等级观察到显著差异。在 3 级 ACR 中差异表达的 22 个基因中，18 个基因也在 2 级 ACR 中差异表达。排斥信号归因于活化的白细胞浸润。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 评分能够区分难治性病例和成功治疗排斥反应的病例。