Background Patients with Down syndrome (DS) are at increased risk for infections and autoimmune disorders. Although several immunological abnormalities were previously found, differences in T cell receptor repertoire have never been shown. Thus we compared the T cell receptor gamma (TRG) repertoire in DS and non-syndromic pediatric patients by next-generation sequencing, in addition to other immunological markers. Methods Genomic DNA was extracted from thymuses of pediatric patients who underwent heart surgery, where six were with DS and six were non-syndromic patients. Peripheral blood counts, T cell subpopulations, thymus TCR excision circles (TRECs), spectratyping, and next-generation sequencing for TRG were analyzed. Results The mean age of the patients was 7 months and the mean lymphocyte count was slightly lower in patients with DS, whereas thymus TREC results were similar to non-syndromic patients ( p = 0.197). The TRG repertoire analysis showed that patients with DS had a significantly larger number of unique TRG sequences, together with decreased clonal expansion. Lastly, the V and J gene usages in the thymus were similar in DS and non-syndromic patients. Conclusions Patients with DS showed increased TRG repertoire diversity with decreased clonal expansion compared to non-syndromic patients. Impact Alterations in T cell receptor gamma repertoire were found in patients with Down syndrome using next-generation sequencing (NGS) technique. Patients showed increased repertoire diversity and decreased clonal expansion compared to controls. These findings add to previous reports on abnormalities of other immune system components in patients with Down syndrome. NGS technique may point out differences not seen by previous methods. Repertoire abnormalities may contribute to those patients’ predisposition to infections and autoimmune diseases.

中文翻译：

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唐氏综合征患者胸腺的免疫和 TRG 库特征

背景 唐氏综合症 (DS) 患者感染和自身免疫性疾病的风险增加。尽管之前发现了几种免疫学异常，但从未显示过 T 细胞受体库的差异。因此，除了其他免疫学标志物外，我们还通过下一代测序比较了 DS 和非综合征儿科患者的 T 细胞受体 γ (TRG) 库。方法从接受心脏手术的儿科患者胸腺中提取基因组DNA，其中6例为DS患者，6例为非综合征患者。分析了外周血计数、T 细胞亚群、胸腺 TCR 切除环 (TREC)、光谱分型和 TRG 的下一代测序。结果 患者平均年龄为 7 个月，DS 患者平均淋巴细胞计数略低，而胸腺 TREC 结果与非综合征患者相似 (p = 0.197)。TRG 谱分析表明，DS 患者具有显着更多的独特 TRG 序列，同时克隆扩增减少。最后，胸腺中 V 和 J 基因的使用在 DS 和非综合征患者中相似。结论与非综合征患者相比，DS 患者表现出增加的 TRG 库多样性和减少的克隆扩增。影响 使用新一代测序 (NGS) 技术在唐氏综合症患者中发现 T 细胞受体 γ 库的改变。与对照组相比，患者表现出增加的曲目多样性和减少的克隆扩增。这些发现增加了之前关于唐氏综合症患者其他免疫系统成分异常的报告。NGS 技术可能会指出以前方法没有发现的差异。组库异常可能会导致这些患者容易感染和自身免疫性疾病。