RNA Sequencing of Human Peripheral Blood Cells Indicates Upregulation of Immune-Related Genes in Huntington's Disease.

Miguel A Andrade-Navarro,Eike J Spruth,Wilfried Nietfeld,Erich E Wanker,Adrián González-López,Tommaso Andreani,Jean-Fred Fontaine,Enrique M Muro,Jenny Russ,Alexei Soldatov,Katja Mühlenberg,Josef Priller,Matthew R Huska,Nancy Mah,Vyacheslav Amstislavskiy

doi:10.3389/fneur.2020.573560

Abstract

Huntington's disease (HD) is an autosomal dominantly inherited neurodegenerative disorder caused by a trinucleotide repeat expansion in the Huntingtin gene. As disease-modifying therapies for HD are being developed, peripheral blood cells may be used to indicate disease progression and to monitor treatment response. In order to investigate whether gene expression changes can be found in the blood of individuals with HD that distinguish them from healthy controls, we performed transcriptome analysis by next-generation sequencing (RNA-seq). We detected a gene expression signature consistent with dysregulation of immune-related functions and inflammatory response in peripheral blood from HD cases vs. controls, including induction of the interferon response genes, IFITM3, IFI6 and IRF7. Our results suggest that it is possible to detect gene expression changes in blood samples from individuals with HD, which may reflect the immune pathology associated with the disease.

Highlights

Huntington’s disease (HD) is an autosomal dominant neurodegenerative disease that commonly presents in mid-life with a triad of motor, cognitive, and psychiatric symptoms
Peripheral venous blood was collected from HD cases, including two pre-symptomatic HD mutation carriers and 9 symptomatic HD cases, and 8 age-matched controls without central nervous system (CNS) disease
The data were examined for differential gene expression, as well as for differential expression of individual exons and transcript isoforms

Summary

INTRODUCTION

Huntington’s disease (HD) is an autosomal dominant neurodegenerative disease that commonly presents in mid-life with a triad of motor, cognitive, and psychiatric symptoms. The levels of mHTT in circulating monocytes and T cells are significantly associated with disease burden scores and caudate atrophy rates in individuals with HD [9]. Expression of a subset of 12 genes clearly distinguished individuals with HD from healthy controls and correlated with disease progression [13]. These findings were not confirmed in a follow-up study that identified the Immediate Early Response 3 gene as a promising candidate [14]. We have used nextgeneration sequencing to analyze differential RNA expression in blood samples from individuals with HD and age-matched controls from a single site in Germany in order to provide additional evidence for a blood signature of the disease

RESULTS

DISCUSSION

Study Participants

ETHICS STATEMENT