Guerra Marjorie-Anne R, Rossetti Maura, Zhang Zhenyu, Zhou Xinkai, Whang Emily C, Venick Robert S, Marcus Elizabeth A, McDiarmid Suzanne V, Farmer Douglas G, Reed Elaine F, Wozniak Laura J
Pediatric Gastroenterology, Hepatology, and Nutrition, David Geffen School of Medicine, UCLA, United States.
Immunogenetics Center, UCLA, United States.
Transpl Immunol. 2018 Dec;51:50-57. doi: 10.1016/j.trim.2018.09.003. Epub 2018 Sep 20.
Immunophenotyping of peripheral blood mononuclear cells has been shown to be a useful, non-invasive method of predicting acute cellular rejection (ACR) following intestinal transplantation (ITx). Our objectives were to characterize differences in the T cell immunophenotype of ITx recipients in peripheral blood samples (1) collected late versus early after ITx and (1) associated with episodes of ACR and infectious enteritis. An IRB-approved, cross-sectional study of ITx recipients was performed. Peripheral blood samples were collected during normal visits and episodes of allograft dysfunction. A total of 38 patients were included in the analysis: 31 ITx recipients (87% liver-inclusive allografts) and 7 intestinal failure control patients. Of the ITx patients, 26 patients were pediatric patients (<21 years). A total of 70 samples were analyzed from ITx recipients, including 51 during normal visits and 19 during episodes of allograft dysfunction (median of 2 samples per patient; range of 1-6 samples per patient). In the late (n = 32) versus early post-ITx (n = 19) normal samples, there was a significantly higher percentage of central memory CD4 T cells (p = .001). In the ACR (n = 5) versus infectious enteritis (n = 14) samples, there was a higher percentage of CD8 T cells expressing HLA-DR (p = .002), CD57 (p < .001), and KLRG1 (p < .001) and a higher percentage of CD4 T cells expressing CD57 (p = .03). Additional studies are needed with larger cohorts to validate these changes in the T cell immunophenotype. Further elucidating T cell immunophenotypes in ITx will lead to a better understanding of immune mechanisms of allograft dysfunction, identification of potential biomarkers in ITx, and optimized selection of immunosuppressive therapies.
外周血单个核细胞的免疫表型分析已被证明是预测肠道移植(ITx)后急性细胞排斥反应(ACR)的一种有用的非侵入性方法。我们的目标是确定ITx受者外周血样本中T细胞免疫表型的差异:(1)ITx后晚期与早期采集的样本;(2)与ACR发作和感染性肠炎相关的样本。对ITx受者进行了一项经机构审查委员会批准的横断面研究。在正常就诊和移植物功能障碍发作期间采集外周血样本。共有38例患者纳入分析:31例ITx受者(87%为包含肝脏的移植物)和7例肠道衰竭对照患者。在ITx患者中,26例为儿科患者(<21岁)。共分析了70份ITx受者的样本,包括51份正常就诊时的样本和19份移植物功能障碍发作时的样本(每位患者中位数为2份样本;每位患者范围为1 - 6份样本)。在ITx后晚期(n = 32)与早期(n = 19)的正常样本中,中枢记忆CD4 T细胞的百分比显著更高(p = 0.001)。在ACR(n = 5)与感染性肠炎(n = 14)样本中,表达HLA - DR(p = 0.002)、CD57(p < 0.001)和KLRG1(p < 0.001)的CD8 T细胞百分比更高,表达CD57的CD4 T细胞百分比更高(p = 0.03)。需要更大样本量的进一步研究来验证T细胞免疫表型的这些变化。进一步阐明ITx中的T细胞免疫表型将有助于更好地理解移植物功能障碍的免疫机制、识别ITx中的潜在生物标志物以及优化免疫抑制治疗的选择。