Blood transcriptome profiling links immunity to disease severity in myotonic dystrophy type 1 (DM1).

The blood transcriptome was examined in relation to disease severity in type I myotonic dystrophy (DM1) patients who participated in the Observational Prolonged Trial In DM1 to Improve QoL- Standards (OPTIMISTIC) study. This sought to a) ascertain if transcriptome changes were associated with increasing disease severity, as measured by the muscle impairment rating scale (MIRS) and b) es-tablish if these changes in mRNA expression and associated biological pathways were also observed in the Dystrophia Myotonica Biomarker Discovery Initiative (DMBDI) microarray dataset in blood (with equivalent MIRS/DMPK repeat length). The changes in gene expression were compared using a number of complementary pathways, gene ontology and upstream regulator analyses, which suggested that symptom severity in DM1 was linked to transcriptomic alterations in innate and adaptive im-munity associated with muscle wasting. Future studies should explore the role of immunity in DM1 in more detail to assess its relevance to DM1.EGA study EGAS00001006926

本研究针对参与「改善生活质量标准的I型肌强直性营养不良（type I myotonic dystrophy, DM1）长期观察性试验（OPTIMISTIC）」的患者，分析了血液转录组与疾病严重程度的关联。本研究旨在实现两大核心目标：其一，明确转录组变化是否与通过肌肉损伤评定量表（muscle impairment rating scale, MIRS）评估的疾病严重程度升高存在关联；其二，验证在肌强直性营养不良生物标志物发现计划（Dystrophia Myotonica Biomarker Discovery Initiative, DMBDI）的血液微阵列数据集（匹配MIRS评分与DMPK基因重复序列长度）中，是否可观测到此类mRNA表达变化及相关生物学通路异常。研究通过多种互补的通路分析、基因本体分析及上游调控因子分析对基因表达差异进行比较，结果表明DM1患者的症状严重程度与伴随肌肉萎缩的固有免疫、适应性免疫相关转录组改变存在关联。未来的研究应更深入地探究免疫在DM1中的作用，以评估其与DM1的相关性。本研究相关欧洲基因组学档案（EGA）研究编号为EGAS00001006926