THE FEASIBILITY OF MECHANISTIC STUDIES ON THE ROLE OF IMMUNITY IN ADOLESCENT IDIOPATHIC SCOLIOSIS

Abstract

Background: The most prominent form of spinal curvature in youth (scoliosis) is Adolescent Idiopathic Scoliosis (AIS). While AIS aetiology is unclear, the role of paraspinal muscle in its genesis has been debated, as These muscles provide spinal stability and motion. It is known that paraspinal muscle (PM) exhibits differential fibrosis on both sides of the spine. As fibrosis is the result of immune system activation, we sought to elucidate the upstream mechanisms of immune-muscle interactions in AIS. Objectives: The primary objective of this thesis was to determine the feasibility of a translational research study (Immunometabolic CONnections to Scoliosis (ICONS) study) procedures. Secondary objectives include the performance of exploratory analyses of macrophages in PM of AIS patients on both sides of the spine. As adiposity is associated with muscle inflammation in the general population, the association of whole-body adiposity with PM macrophage content and/or phenotype was investigated. Hypothesis: We tested the hypothesis that ICONS study protocols are feasible and that PM macrophage populations are different on both sides of the spine. Furthermore, we hypothesized that increasing adiposity positively correlates with PM macrophage infiltration. Results: We observed that all pre-set feasibility criteria were achieved or surpassed, except that of recruitment rate. PM total macrophage content was not different on either side of the scoliotic curve; however, a trend of predominance of anti-inflammatory macrophages on the convex side of the scoliotic curve was noted. PM macrophage content correlated positively with adiposity. Conclusions: Adopting the ICONS study procedures for the full study is feasible. Continued investigations of immune system role in PM of AIS patients may identify therapeutic targets to aid AIS treatment and prevention.