Blood Transcriptome Profiling Links Immunity to Disease Severity in Myotonic Dystrophy Type 1 (DM1)

Abstract

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) establish 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 immunity associated with muscle-wasting. Future studies should explore the role of immunity in DM1 in more detail to assess its relevance to DM1.

A cyclic pyrrole-imidazole polyamide reduces pathogenic RNA in CAG/CTG triplet repeat neurological disease models

“…Interestingly, the dysregulated genes in CUG300 mice were also enriched in the immune system (Figure 6D). Consistent with this, upregulated genes in the lens epithelia of patients with DM1 were enriched in the innate immune response, and the changes in the immune response system have been suggested to correlate with disease severity (78,79). Immune dysfunction, such as T cell activation and cytokine production, is also a key event in neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease (80).…”

Individual transcriptomic response to strength training for patients with myotonic dystrophy type 1

“…Other mechanisms commonly studied in the context of DM1 are increased levels of CUGBP1 (13), repeat-associated non-AUG translation (14), microRNA dysregulation (15), and the sequestration of transcription factors by the toxic RNAs (16). A lesser-studied aspect of DM1 is differential gene expression (DGE); however, dysregulation of gene expression has been identified across multiple tissues in patients with DM1 (17)(18)(19)(20).…”