Anti-satellite Glia Cell IgG Antibodies Are Linked to Symptoms and Brain Metabolites in Fibromyalgia

Background & Aims

Recent translational research suggested that fibromyalgia may be an autoimmune disorder with pathogenic mechanisms mediated by a peripheral, pain-inducing action of immunoglobulin G (IgG) antibodies binding to satellite glia cells (SGC) in the dorsal root ganglia [1]. A clinical assessment of the postulated autoimmunity showed that fibromyalgia subjects (FMS) had elevated levels of antibodies against SGC (termed anti-SGC IgG) compared to healthy controls and that anti-SGC IgG were related with a more severe disease status [2]. The current study aimed to determine whether anti-SGC IgG have also a relation with central mechanisms, besides driving pain through peripheral mechanisms, as indirectly shown so far. In a larger cohort of FMS, we wanted to first confirm the relation between anti-SGC IgG and pain-related clinical measures. Secondly, we explored the associations of these autoantibodies with brain metabolite concentrations and pressure-evoked cerebral pain processing in FMS.

Methods

Data were collected on two consecutive days. Day 1 consisted of 1) administering validated questionnaires, 2) collecting serum samples for the quantification of anti-SGC IgG, 3) determining pressure pain thresholds (PPTs) in order to assess pain sensitivity, 4) calibrating individually painful pressures for their use during functional magnetic resonance imaging (fMRI), 5) conditioning the subjects to associate color cues with pressure stimulations of different intensities (familiarization to pressure pain paradigm on day 2). Day 2 was the neuroimaging session, which consisted in performing single-voxel proton magnetic resonance spectroscopy (MRS) in bilateral thalamus and right rostral anterior cingulate cortex (rACC) for the assessment of a wide spectrum of metabolites, as well as task-based fMRI. During fMRI, FMS received individually calibrated painful pressure stimulations corresponding to low and high pain intensities.

Results

Our findings confirmed a positive correlation between anti-SGC IgG levels and clinical measures assessing condition severity and pain intensity. In addition, FMS with high anti-SGC IgG levels reported higher pain intensity and a worse disease status than FMS with low anti-SGC IgG levels. Conversely, sensitivity to pressure pain was neither related to nor differed based on anti-SGC IgG levels. Furthermore, anti-SGC IgG levels were negatively correlated with metabolites such as scyllo-inositol in thalamus and rACC as well as with total choline and macromolecule 12 in thalamus, thus speculatively indicating a link between anti-SGC IgG levels and metabolite-related glia processes in the brain of FMS. Lastly, the cerebral processing of evoked pressure pain was neither related to nor differed based on anti-SGC IgG levels.

Conclusions

Our results showing that FMS with high anti-SGC IgG levels had a more intense current pain and a higher impact of FM support the clinical relevance of anti-SGC IgG for spontaneous pain in FMS. Conversely, we speculate that evoked pain might not be related to anti-SGC IgG levels, as suggested by our results failing to show differences between FMS with high and low anti-SGC IgG levels, or an association of anti-SGC IgG with, for example, PPTs or pressure-evoked cerebral pain processing. Our findings regarding the negative correlation between anti-SGC IgG levels and, specifically, the brain metabolites scyllo-inositol and total choline merit further investigation, particularly since low levels of these metabolites in FMS were shown to respectively correlate with more severe FM symptoms and higher pain intensity.

References

The findings from this research were recently published in the journal Brain, Behavior, and Immunity (refer to the details below). However, the research has not yet been presented at any conferences.

Fanton, S., Menezes, J., Krock, E., Sandström, A., Tour, J., Sandor, K., Jurczak, A., Hunt, M., Baharpoor, A., Kadetoff, D., & Jensen, K.B. (2023). Anti-satellite glia cell IgG antibodies in fibromyalgia patients are related to symptom severity and to metabolite concentrations in thalamus and rostral anterior cingulate cortex. Brain, Behavior, and Immunity, 114, 371-382. https://doi.org/10.1016/j.bbi.2023.09.003

[1] Goebel, A., Krock, E., Gentry, C., Israel, M. R., Jurczak, A., Urbina, C. M., Sandor, K., Vastani, N., Maurer, M., Cuhadar, U., Sensi, S., Nomura, Y., Menezes, J., Baharpoor, A., Brieskorn, L., Sandström, A., Tour, J., Kadetoff, D., Haglund, L., Kosek, E., Bevan, S., Svensson, C. I., & Andersson, D. A. (2021). Passive transfer of fibromyalgia symptoms from patients to mice. Journal of Clinical Investigation, 131(13), e144201. https://doi.org/10.1172/JCI144201

[2] Krock, E., Morado-Urbina, C. E., Menezes, J., Hunt, M. A., Sandström, A., Kadetoff, D., Tour, J., Verma, V., Kultima, K., Haglund, L., Meloto, C. B., Diatchenko, L., Kosek, E., & Svensson, C. I. (2023). Fibromyalgia patients with elevated levels of anti–satellite glia cell immunoglobulin G antibodies present with more severe symptoms. Pain, 164(8), 1828-1840. https://doi.org/10.1097/j.pain.0000000000002881

Presenting Author

Silvia Fanton

Poster Authors

Silvia Fanton

PhD.

A.A. Martinos Center for Biomedical Imaging, MGH, Harvard Medical School

Lead Author

Anti-satellite Glia Cell IgG Antibodies Are Linked to Symptoms and Brain Metabolites in Fibromyalgia

Background & Aims

Methods

Results

Conclusions

References

Presenting Author

Silvia Fanton

Poster Authors

Silvia Fanton

Joana Menezes

Emerson Krock

Angelica Sandström

Jeanette Tour

Katalin Sandor

Alexandra Jurczak

Matthew Hunt

Azar Baharpoor

Diana Kadetoff

Karin jensen Jensen (PhD)

Peter Fransson

Isabel Ellerbrock

Rouslan Sitnikov

Camilla Svensson

Eva Kosek

Topics

IASP 2024 World Congress on Pain