Institute of New Frontier Stroke Research, Hallym University College of Medicine, Chuncheon 24253, Korea.
Genetic and Research Inc., Chuncheon 24253, Korea.
Int J Mol Sci. 2020 Apr 29;21(9):3149. doi: 10.3390/ijms21093149.
Little is known of the adaptive immune response to subarachnoid hemorrhage (SAH). This study was the first to investigate whether T cell receptor (TCR) immune repertoire may provide a better understanding of T cell immunology in delayed cerebral ischemia (DCI). We serially collected peripheral blood in five SAH patients with DCI. High-throughput sequencing was used to analyze the TCR β chain (TCRB) complimentary determining regions (CDR) 3 repertoire. We evaluated the compositions and variations of the repertoire between admission and the DCI period, for severe DCI and non-severe DCI patients. Clonality did not differ significantly between admission and DCI. Severe DCI patients had significantly lower clonality than non-severe DCI patients ( value = 0.019). A read frequency of 0.005% ≤ - < 0.05% dominated the clonal expansion in non-severe DCI patients. Regarding repertoire diversity, severe DCI had a higher diversity score on admission than non-severe DCI. The CDR3 lengths were similar between admission and DCI. Among 728 annotated V-J gene pairs, we found that the relative frequencies of two V-J pairs were different at the occurrence of DCI than at admission, with T cells increasing by over 15%. TCRB CDR3 repertoires may serve as biomarkers to identify severe DCI patients.
对蛛网膜下腔出血 (SAH) 的适应性免疫反应知之甚少。这项研究首次探讨了 T 细胞受体 (TCR) 免疫受体库是否可以更好地了解迟发性脑缺血 (DCI) 中的 T 细胞免疫学。我们连续采集了 5 例 DCI 患者的外周血。使用高通量测序分析 TCRβ链 (TCRB) 互补决定区 (CDR)3 受体库。我们评估了入院和 DCI 期间、严重 DCI 和非严重 DCI 患者之间的受体库组成和变化。入院和 DCI 之间的克隆性没有显著差异。严重 DCI 患者的克隆性明显低于非严重 DCI 患者（value=0.019）。在非严重 DCI 患者中，克隆扩展以 0.005%≤-<0.05%的读取频率为主。关于受体库多样性，严重 DCI 患者入院时的多样性评分高于非严重 DCI 患者。CDR3 长度在入院和 DCI 之间相似。在 728 对注释的 V-J 基因对中，我们发现发生 DCI 时的两个 V-J 对的相对频率与入院时不同，T 细胞增加了 15%以上。TCRB CDR3 受体库可作为识别严重 DCI 患者的生物标志物。
