Searching for blood biomarkers and treatment targets in Women with fibromyalgia – Protein interaction patterns and anti-satellite glia cell IgG antibodies as promising candidates

Background
Recent studies suggest that autoreactive immunoglobulin G (IgG) antibodies binding to satellite glia cells (anti-SGC IgG) in the dorsal root ganglia influence pain intensity in a subgroup of fibromyalgia subjects (FMS), thus indicating altered immune activation. The main aim of this study was to identify proteins distinguishing female FMS from female healthy controls (HC) and within the FM group, proteins distinguishing FMS with high vs low levels of anti-SGC IgG. The secondary aim was to assess the associations between serum proteins and anti-SGC IgG, respectively, and FM symptoms.
Methods
Anti-SGC IgG was quantified using an immunofluorescence assay. Proteins in serum were assessed using Olink® Explore 384 Inflammation panel, regarding differences between FMS ( = 93) and HC (n = 40) and regarding differences between FMS with high (≥50 %) and low (<50 %) anti-SGC IgG, respectively. Proteins found to differ between groups (VIP ≥ 1.3) were further analyzed regarding protein-interactions using the software tool STRING (FM vs HC n = 56, high vs low anti-SGC IgG n = 55). Results from the FM group were also compared with two nociceptive pain conditions.ResultsIn FMS, a cluster of immune system-related proteins was found among upregulated proteins, including CD40 and CD40L, with central roles in humoral immune response. CD40 levels were associated with more severe FM symptoms. In contrast, a cluster of tissue development-/regeneration-related proteins was found among downregulated proteins, this was not seen in nociceptive pain conditions. In FMS with high anti-SGC IgG, clusters dominated by immune system-related proteins were found among both upregulated and downregulated proteins. The cluster of upregulated proteins included CD79b, a protein necessary for B-cell receptor function, and CD4, a co receptor needed for T cell activation, thus with central role in activating various immune responses, including B-cell activation. Positive correlations were seen between some of these proteins and symptoms. On the contrary, several of the downregulated proteins correlated negatively to symptoms.ConclusionOur data support the involvement of the immune system in FM and indicate that further studies on autoimmune mechanisms, proteomics, and protein interaction analysis could lead to new objective diagnostic criteria identifying FMS likely to benefit from immunomodulatory treatments.