Abstract:
Introduction: Neuroinflammation is a known pathophysiologic mechanism in multiple sclerosis and a proposed mechanism in fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Positron Emission Tomography (PET) imaging of the translocator protein (TSPO) has been widely used to measure neuroinflammation, though second-generation ligands are highly sensitive to a single nucleotide polymorphism, rs6971, resulting in high, mixed, and low affinity binders. It is unknown whether this polymorphism is associated with neuroinflammatory disorders.
Materials and methods: Eighty-six total participant genotypes for TSPO binding affinity were identified through Sanger sequencing (30 fibromyalgia, 21 ME/CFS, 11 multiple sclerosis, and 24 healthy controls). Associations between patient group and genotype were assessed with Fisher’s Exact test. Associations between genotype and symptom severity from self-report questionnaires were assessed with Kruskal-Wallis tests.
Results: In the present study individuals with fibromyalgia, (ME/CFS), or multiple sclerosis were more likely to have a mixed- or low-affinity genotypes compared to healthy controls. Presence of the low or mixed genotypes were also associated with greater self-reported fatigue severity and depressive symptoms.
Discussion: These findings should be confirmed in larger samples but suggest functional consequences of rs6971 polymorphism that may be related to the pathophysiology of pain and fatigue illnesses.
Source: Jones C, Younger J. Fibromyalgia, Chronic Fatigue Syndrome, and Multiple Sclerosis are associated with lower translocator protein binding affinity genotypes. medRxiv [Preprint]. 2026 Oct 21:2026.10.19.26365953. doi: 10.64898/2026.10.19.26365953. PMID: 42996068; PMCID: PMC13738865. https://pmc.ncbi.nlm.nih.gov/articles/PMC13738865/ (Full text)