Correlation between gene expression and MRI STIR signals in patients with chronic low\xa0back pain and Modic changes indicates immune involvement

Bendik Slagsvold Winsvold,Jörg Aßmus,Veronica Sørensen,Marianne Thorsø,Siv Krüger Claussen,Hege Andersen,Lars Grøvle,Lars Christian Haugli Bråten,Siri Tennebø Flåm,Elisabeth Gjefsen,Britt Elin Lurud,Audny Anke,Ansgar Espeland,Magnus Dehli Vigeland,Thor Einar Holmgard,Knut Morten Huneide,Karianne Wiger Gammelsrud,Guro Kjos,Terese Fors,Linda M Pedersen ,Jan Sture Skouen,Elina Iordanova Schistad,Hilde Presberg,Maja Wilhelmsen,Per Martin Kristoffersen,Christian Hellum,Sigrun Randen,Erling D Andersen ,Olav Lutro,Vidar Rao,John‐Anker Zwart ,Fredrik Granvigen,Monica Wigemyr,Kjersti Storheim,Jens Ivar Brox,Gunn Hege Marchand,Nils Vetti,Thomas Kadar ,Anne Julsrud Haugen,Benedicte A Lie ,Anne Froholdt,Ida Beate Øyen Østhus ,Mads Peder Rolfsen,Øystein P Nygaard ,Margreth Grotle,Null Author_Id

doi:10.1038/s41598-021-04189-5

Abstract

Disability and distress caused by chronic low back pain (LBP) lacking clear pathoanatomical explanations cause huge problems both for patients and society. A subgroup of patients has Modic changes (MC), identifiable by MRI as vertebral bone marrow lesions. The cause of such changes and their relationship to pain are not yet understood. We explored the pathobiology of these lesions using profiling of gene expression in blood, coupled with an edema-sensitive MRI technique known as short tau inversion recovery (STIR) imaging. STIR images and total RNA from blood were collected from 96 patients with chronic LBP and MC type I, the most inflammatory MC state. We found the expression of 37 genes significantly associated with STIR signal volume, ten genes with edema abundancy (a constructed combination of STIR signal volume, height, and intensity), and one gene with expression levels significantly associated with maximum STIR signal intensity. Gene sets related to interferon signaling, mitochondrial metabolism and defense response to virus were identified as significantly enriched among the upregulated genes in all three analyses. Our results point to inflammation and immunological defense as important players in MC biology in patients with chronic LBP.

Highlights

Disability and distress caused by chronic low back pain (LBP) lacking clear pathoanatomical explanations cause huge problems both for patients and society
We aimed at improving the pathobiological understanding of Modic changes (MC) type I related short tau inversion recovery (STIR) signal increases in patients with chronic LBP, using whole blood gene expression profiling and pathway analysis
The patients had suffered from LBP with a duration of more than 6 months and had MC type I or II in the vertebral body at the same disc level as a lumbar disc herniation verified on magnetic resonance imaging (MRI) within the preceding 2 years

Summary

Introduction

Disability and distress caused by chronic low back pain (LBP) lacking clear pathoanatomical explanations cause huge problems both for patients and society. We aimed at improving the pathobiological understanding of MC type I related STIR signal increases in patients with chronic LBP, using whole blood gene expression profiling and pathway analysis. The most significantly differentially expressed protein coding genes resulting from the analysis of STIR volume, were GLYATL2 (adjusted p-value (padj) = 6.3e−04), IFI27 (padj = 9.9e−04), MYO18B (padj = 5.6e−03) and APOLD1 (padj = 7.7e−03).

Results

Conclusion