Fibromyalgia patients with high levels of anti-satellite glia cell IgG antibodies present with more severe symptoms

Abstract

Objective: Transferring fibromyalgia patient IgG to mice induces pain-like behaviour and fibromyalgia IgG binds mouse and human satellite glia cells (SGCs). These findings suggest that autoantibodies could be part of fibromyalgia pathology. However, it is unknown how frequently fibromyalgia patients have anti-SGC antibodies and how anti-SGC antibodies associate with disease severity. Methods: We quantified serum or plasma anti-SGC IgG levels in two fibromyalgia cohorts from Sweden and Canada using an indirect immunofluorescence murine cell culture assay. Fibromyalgia serum IgG binding to human SGCs in human dorsal root ganglia tissue sections was assessed by immunofluorescence (n=14/group). Results: In the cell culture assay anti-SGC IgG levels were increased in both fibromyalgia cohorts compared to controls. Elevated anti-SGC IgG was associated with higher levels of self-reported pain in both cohorts, and higher fibromyalgia impact questionnaire scores and increased pressure sensitivity in the Swedish cohort. Anti-SGC IgG levels were not associated with fibromyalgia duration. Swedish FM patients were clustered into FM-severe and FM-mild groups and the FM-severe group had elevated anti-SGC IgG compared to the FM-mild and controls. Anti-SGC IgG levels detected in culture were positively correlated with increased binding to human SGCs. Moreover, the FM-severe group had elevated IgG binding to human SGCs compared to the FM-mild and control groups. Conclusions: A subset of fibromyalgia patients have elevated levels of anti-SGC antibodies, and the antibodies are associated with more severe fibromyalgia severity. Screening fibromyalgia patients for anti-SGC antibodies could provide a path to personalized treatment options that target autoantibodies and autoantibody production.

A network of CD163+macrophages monitors enhanced permeability at the blood-dorsal root ganglion barrier

“…Caveolar transcytosis represents a mechanism that could potentially be pharmacologically targeted to reduce DRG endothelial permeability, or alternatively co-opted to deliver drugs into the DRG parenchyma (Kiseleva et al, 2018; Marchetti et al, 2019). This could be desirable in sensory ganglionopathies (Amato and Ropper, 2020), which include paraneoplastic and autoimmune conditions, infections, platinum-based chemotherapy (Dzagnidze et al, 2007; Gupta and Bhaskar, 2016), and likely also fibromyalgia (Goebel et al, 2021; Martínez-Lavín, 2021; Krock et al, 2023).…”

Applying Lessons From Rheumatology to Better Understand Long COVID

“…Microglial activation has been considered a marker for localized brain neuroimmune mechanisms and a potential key mechanism in central (nociplastic) pain (60). A subset of patients with FM had elevated levels of anti-satellite glial cell antibodies, but this was not associated with cytokine release or with systemic inflammation (61). It has been suggested that the nociplastic pain characteristic of FM, ME/CFS, and long COVID may share similar glial brain activation pathways (62,63).…”

Fibromyalgia Pathophysiology

“…The results demosntrated a correlation between binding of IgG to SGCs and fibromylagia disease severity. These finds show potential for a anti-SGC antibody screening test for FMS to assist personalized treatment options that target autoantibodies [ 30 ].…”