Fibromyalgia (FM) is a poorly understood chronic condition characterized by widespread musculoskeletal pain, fatigue, and cognitive difficulties. While mounting evidence suggests a role for neuroinflammation, no study has directly provided evidence of brain glial activation in FM. In this study, we conducted a Positron Emission Tomography (PET) study using [C]PBR28, which binds to the translocator protein (TSPO), a protein upregulated in activated microglia and astrocytes. To enhance statistical power and generalizability, we combined datasets collected independently at two separate institutions (Massachusetts General Hospital [MGH] and Karolinska Institutet [KI]). In an attempt to disentangle the contributions of different glial cell types to FM, a smaller sample was scanned at KI with [C]--deprenyl-D PET, thought to primarily reflect astrocytic (but not microglial) signal. Thirty-one FM patients and 27 healthy controls (HC) were examined using [C]PBR28 PET. 11 FM patients and 11 HC were scanned using [C]--deprenyl-D PET. Standardized uptake values normalized by occipital cortex signal (SUVR) and distribution volume (V) were computed from the [C]PBR28 data. [C]--deprenyl-D was quantified using λ k. PET imaging metrics were compared across groups, and when differing across groups, against clinical variables. Compared to HC, FM patients demonstrated widespread cortical elevations, and no decreases, in [C]PBR28 V and SUVR, most pronounced in the medial and lateral walls of the frontal and parietal lobes. No regions showed significant group differences in [C]--deprenyl-D signal, including those demonstrating elevated [C]PBR28 signal in patients (p's ≥ 0.53, uncorrected). The elevations in [C]PBR28 V and SUVR were correlated both spatially (i.e., were observed in overlapping regions) and, in several areas, also in terms of magnitude. In exploratory, uncorrected analyses, higher subjective ratings of fatigue in FM patients were associated with higher [C]PBR28 SUVR in the anterior and posterior middle cingulate cortices (p's < 0.03). SUVR was not significantly associated with any other clinical variable. Our work provides the first in vivo evidence supporting a role for glial activation in FM pathophysiology. Given that the elevations in [C]PBR28 signal were not also accompanied by increased [C]--deprenyl-D signal, our data suggests that microglia, but not astrocytes, may be driving the TSPO elevation in these regions. Although [C]--deprenyl-D signal was not found to be increased in FM patients, larger studies are needed to further assess the role of possible astrocytic contributions in FM. Overall, our data support glial modulation as a potential therapeutic strategy for FM.
IntroductionPrior studies have demonstrated an increased frequency of antibodies to Porphyromonas gingivalis (Pg), a leading agent of periodontal disease, in rheumatoid arthritis (RA) patients. However, these patients generally had long-standing disease, and clinical associations with these antibodies were inconsistent. Our goal was to examine Pg antibody responses and their clinical associations in patients with early RA prior to and after disease-modifying antirheumatic drug (DMARD) therapy.MethodsSerum samples from 50 DMARD-naïve RA patients were tested using an enzyme-linked immunosorbent assay with whole-Pg sonicate. For comparison, serum samples were tested from patients with late RA, patients with other connective tissue diseases (CTDs), age-similar healthy hospital personnel and blood bank donors. Pg antibody responses in early RA patients were correlated with standard RA biomarkers, measures of disease activity and function.ResultsAt the time of enrollment, 17 (34%) of the 50 patients with early RA had positive immunoglobulin G (IgG) antibody responses to Pg, as did 13 (30%) of the 43 patients with late RA. RA patients had significantly higher Pg antibody responses than healthy hospital personnel and blood bank donors (P < 0.0001). Additionally, RA patients tended to have higher Pg antibody reactivity than patients with other CTDs (P = 0.1), and CTD patients tended to have higher Pg responses than healthy participants (P = 0.07). Compared with Pg antibody-negative patients, early RA patients with positive Pg responses more often had anti-cyclic citrullinated peptide (anti-CCP) antibody reactivity, their anti-CCP levels were significantly higher (P = 0.03) and the levels of anti-Pg antibodies correlated directly with anti-CCP levels (P < 0.01). Furthermore, at the time of study entry, the Pg-positive antibody group had greater rheumatoid factor values (P = 0.04) and higher inflammatory markers (erythrocyte sedimentation rate, or ESR) (P = 0.05), and they tended to have higher disease activity scores (Disease Activity Score based on 28-joint count (DAS28)-ESR and Clinical Disease Activity Index) and more functional impairment (Health Assessment Questionnaire). In Pg-positive patients, greater disease activity was still apparent after 12 months of DMARD therapy.ConclusionsA subset of early RA patients had positive Pg antibody responses. The responses correlated with anti-CCP antibody reactivity and to a lesser degree with ESR values. There was a trend toward greater disease activity in Pg-positive patients, and this trend remained after 12 months of DMARD therapy. These findings are consistent with a role for Pg in disease pathogenesis in a subset of RA patients.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.