Pidala Joseph, Bloom Gregory C, Eschrich Steven, Sarwal Minnie, Enkemann Steve, Betts Brian C, Beato Francisca, Yoder Sean, Anasetti Claudio
Blood and Marrow Transplantation, Moffitt Cancer Center, Tampa, FL, United States of America.
Bioinformatics, Moffitt Cancer Center, Tampa, FL, United States of America.
PLoS One. 2015 Mar 16;10(3):e0117001. doi: 10.1371/journal.pone.0117001. eCollection 2015.
Biologic markers of immune tolerance may facilitate tailoring of immune suppression duration after allogeneic hematopoietic cell transplantation (HCT). In a cross-sectional study, peripheral blood samples were obtained from tolerant (n = 15, median 38.5 months post-HCT) and non-tolerant (n = 17, median 39.5 post-HCT) HCT recipients and healthy control subjects (n = 10) for analysis of immune cell subsets and differential gene expression. There were no significant differences in immune subsets across groups. We identified 281 probe sets unique to the tolerant (TOL) group and 122 for non-tolerant (non-TOL). These were enriched for process networks including NK cell cytotoxicity, antigen presentation, lymphocyte proliferation, and cell cycle and apoptosis. Differential gene expression was enriched for CD56, CD66, and CD14 human lineage-specific gene expression. Differential expression of 20 probe sets between groups was sufficient to develop a classifier with > 90% accuracy, correctly classifying 14/15 TOL cases and 15/17 non-TOL cases. These data suggest that differential gene expression can be utilized to accurately classify tolerant patients following HCT. Prospective investigation of immune tolerance biologic markers is warranted.
免疫耐受的生物标志物可能有助于调整异基因造血细胞移植(HCT)后的免疫抑制持续时间。在一项横断面研究中,从耐受的(n = 15,HCT后中位时间38.5个月)和不耐受的(n = 17,HCT后中位时间39.5个月)HCT受者以及健康对照者(n = 10)获取外周血样本,用于分析免疫细胞亚群和差异基因表达。各组之间的免疫亚群没有显著差异。我们鉴定出耐受(TOL)组特有的281个探针集和不耐受(非TOL)组特有的122个探针集。这些探针集在包括NK细胞细胞毒性、抗原呈递、淋巴细胞增殖以及细胞周期和凋亡的过程网络中富集。差异基因表达在CD56、CD66和CD14人类谱系特异性基因表达中富集。两组之间20个探针集的差异表达足以构建一个准确率> 90%的分类器,正确分类14/15例TOL病例和15/17例非TOL病例。这些数据表明,差异基因表达可用于准确分类HCT后的耐受患者。有必要对免疫耐受生物标志物进行前瞻性研究。