Biology subjects

Kosek, E.

Publications and source records attributed to Kosek, E..

8 recordsLinked to original sources

bioRxiv2025

Exploring the neuroimmune cellular landscape in the skin of subjects with fibromyalgia.

Fibromyalgia (FM) is a chronic disorder involving widespread pain, fatigue, and cognitive impairment. Although its pathogenesis remains uncertain, FM patients exhibit hypersensitivity, reduced intraepidermal nerve fiber density (IENFD), and more recently shown, skin immune dysregulation, possibly manifesting in cutaneous alterations in various cell populations. To characterize the cutaneous cellular landscape in FM, we assessed the sensory profile and skin cell populations across different layers within the same cohort. FM patients, compared to healthy controls (HC), showed lower pain thresholds across multiple body areas, with no differences in thermal detection. While our findings confirm previous reports for reduced PGP9.5+ IENF and increased density in mast cells in FM, we also identified novel changes, particularly in the dermis. We observed elongated thinly myelinated NF200+ fibers and reduced density in non-nerve-associated S100B+ Schwann cells in FM compared to HC. Notably, dermal CD68+ and CD163+ populations were significantly reduced in FM, accompanied by morphological changes. The CD163+ population correlated negatively and significantly against IENFD. These findings suggest that, beyond intraepidermal nerve loss, FM involves broader neuroimmune alterations in the skin, particularly within the dermis, offering new insights into its pathophysiology and establishing a foundation for future studies exploring the functional implications of these changes. SUMMARYAmong the alterations observed in patients with fibromyalgia (FM) are changes in skin innervation and differences in the density of certain immune cell populations. To better characterize FM from an integral perspective, we examined both the sensory profile and the cutaneous cellular landscape of FM patients in comparison with healthy controls (HC). FM patients exhibited lower pain thresholds across multiple body areas, with no differences in thermal detection. Consistent with previous findings, FM skin biopsies revealed reduced intraepidermal nerve fiber density and increased mast cell numbers. Beyond these known alterations, our study identified novel dermal changes, including elongated thinly myelinated NF200+ fibers, reduced density of non-nerve-associated S100B+ Schwann cells, and decreased CD68+ and CD163+ macrophage populations exhibiting morphological alterations. Notably, CD163+ cell density correlated negatively with intraepidermal nerve fiber density, highlighting potential neuroimmune mechanisms underlying the pathophysiology of FM.

immunology↗

bioRxiv2025

Offset analgesia and onset hyperalgesia: A comparison between women with non-suicidal self-injury and healthy women

IntroductionIndividuals who engage in non-suicidal self-injury (NSSI) exhibit reduced pain sensitivity compared to the general population. It has been argued that this hypoalgesic characteristic may be attributable to hyper-effective pain modulation. However, empirical support for this theory remains inconsistent. ObjectiveThe aim of the study was to use a combined offset analgesia (OA) and onset hyperalgesia (OH) protocol to investigate if women with NSSI have a propensity to inhibit nociceptive signals to a higher degree (stronger OA response) and facilitate nociceptive signals to a lesser degree (weaker OH response), compared to a control group. MethodsData was collected from 76 women, 18-35 age (37 with NSSI and 39 healthy controls). The OA and OH protocol was combined with functional magnetic resonance imaging (fMRI). ResultsThe NSSI group displayed a weaker OH response, compared to the control group. This suggests that women with NSSI do not facilitate nociceptive signals to the same extent as healthy women. However, there were no significant differences between the groups regarding OA. Across all participants, we observed stronger activation in the primary sensory cortex during the OH condition, compared to the control condition. ConclusionsThe results offer partial support for the general hypothesis that women with NSSI demonstrate enhanced pain modulation.

neuroscience↗

bioRxiv2024

Microbially produced bile acids are associated with high levels of IgG autoantibodies and worse mental wellbeingin fibromyalgia subjects

Fibromyalgia (FM) is a disease primarily associated with chronic widespread pain, but other common symptoms are anxiety and depression. We previously proposed that autoimmunity contributes to FM based on findings of increased immunoglobulin G binding to satellite glial cells (anti-SGC IgG) in FM subjects compared to healthy controls (HC). Emerging research suggests that an altered gut microbiota composition is connected to psychological symptoms in FM rather than pain. Gut microbiota can produce or alter bile acids (BAs) and short-chain fatty acids (SCFAs), which have immune and inflammatory functions. Here, we investigate alterations in BA and SCFA concentrations in FM subjects compared to healthy controls (HC) and potential associations with FM symptoms and anti-SGC IgG levels. Bile acids and SCFAs were quantified using liquid chromatography coupled with high-resolution mass spectrometry and anti-SGC IgG levels were assessed with immunocytochemistry. The correlations between FM symptoms, anti-SGC IgG levels, and serum concentrations of 24 BAs and 11 SCFAs in 35 FM subjects and 32 matched HC were examined. Fibromyalgia subjects had significantly higher levels of microbially produced BAs than HC. Strikingly, 11 out of 24 BAs were significantly elevated in FM subjects with high, compared to those with low, anti-SGC IgG levels. Concentrations of specific BAs were associated with increased disease severity and worse mental well-being. These results revealed increased levels of secondary BAs in FM subjects compared to HC. The strong association between BAs, anti-SGC IgG levels, and mental well-being may help elucidate the importance of BAs in the psychological symptoms of FM. Significance statementFibromyalgia (FM) is a chronic pain syndrome that significantly impacts an individuals quality of life. In addition to persistent pain, people with FM often experience depression, anxiety, and irritable bowel syndrome. Previously, we identified autoantibodies that bind to satellite glial cells in the dorsal root ganglia associated with more severe FM symptoms. Our current results demonstrate a novel association between these autoantibodies in FM and bile acids (BAs). Bile acids are essential for lipid metabolism but also act as signaling molecules. We show that patients with elevated levels of autoantibodies also exhibit increased levels of BAs. Furthermore, the BAs strongly correlate with worse FM symptom severity, particularly affecting mental well-being. Our study suggests that lowering BA levels could alleviate the psychological symptoms associated with FM.

neuroscience↗

bioRxiv2024

Fibromyalgia patients have altered lipid concentrations associated with disease symptom severity and anti-satellite glial cell IgG antibodies

Autoimmunity and immunoglobulin G (IgG) autoantibodies may contribute to pain in a subset of fibromyalgia (FM) patients. Previously, we saw that IgG from FM patients induces pain-like behavior in mice and binds to satellite glial cells (anti-SGC IgG). The anti-SGC IgG levels were also associated with more severe symptomatology. Lipid metabolism in FM subjects is altered with lysophosphatidylcholines (LPCs) acting as pain mediators. The relationship between autoantibodies, lipid metabolism, and FM symptomatology remains unclear. We analyzed serum lipidomics with liquid chromatography mass spectrometry, anti-SGC IgG levels, and clinical measures in 35 female FM subjects and 33 age- and body mass index-balanced healthy controls (HC). Fibromyalgia subjects with higher anti-SGC IgG levels experienced more intense pain than those with lower levels. Sixty-three lipids were significantly altered between FM subjects and HC or between FM subjects with severe (FM severe) and mild symptoms (FM mild). Compared to HC, FM subjects had lower concentrations of lipid species belonging to the classes LPC (n = 10), lysophosphatidylethanolamine (n = 7), phosphatidylcholine (n = 4), and triglyceride (n = 5), but higher concentrations of diglyceride (n = 3). Additionally, FM severe had higher LPC 19:0, 22:0, and 24:1 and lower sphingomyelin (n = 9) concentrations compared to FM mild. A positive association was seen for LPC 22:0 and 24:1 with pain intensity and anti-SGC IgG levels in FM subjects. Taken together, our results suggest an association between altered lipid metabolism and autoimmune mechanisms in FM. PerspectiveOur results suggest an association between the postulated autoimmunity in FM and lipids that can act as pain mediators.

neuroscience↗

bioRxiv2022

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

ObjectiveTransferring 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. MethodsWe 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). ResultsIn 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. ConclusionsA 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.

neuroscience↗

bioRxiv2021

Lysophophatidyl-choline 16:0 mediates persistent joint pain through Acid-Sensing Ion Channel 3: preclinical and clinical evidences

Rheumatic diseases are often associated to debilitating chronic joint pain, which remains difficult to treat and requires new therapeutic strategies. Here, we describe increased content of lysophosphatidyl-choline (LPC) 16:0 in the knee synovial fluids of two independent cohorts of patients with painful joint diseases. If LPC16:0 levels correlated with pain in patients with osteoarthritis (OA), they do not appear to be the hallmark of a particular joint disease. We found that intra-articular injections of LPC16:0 in mouse produce chronic pain and anxiety-like behaviors in both males and females with no apparent inflammation, peripheral nerve sprouting and damage, nor bone alterations. LPC16:0-induced persistent pain state is dependent on peripheral Acid-Sensing Ion Channel 3 (ASIC3), ultimately leading to central sensitization. LPC16:0 and ASIC3 thus appear as key players of chronic joint pain with potential implications in OA and possibly across others rheumatic diseases.

neuroscience↗

bioRxiv2019

Passive transfer of fibromyalgia pain from patients to mice.

Fibromyalgia syndrome (FMS) is a chronic pain condition characterized by widespread pain and tenderness1,2. The etiology and pathophysiology of fibromyalgia are unknown and there are no effective treatments. Here we show that sensory hypersensitivity in FMS is caused by autoantibodies that act by sensitizing nociceptive sensory neurons. Administration of IgG from FMS patients increased mouse pain sensitivities to stimulation with mechanical pressure and cold. In contrast, transfer of IgG depleted samples from FMS patients or IgG from healthy control subjects had no effect on pain sensitivity. Sensory nerve fibres in ex vivo skin-nerve preparations from mice treated with FMS IgG were hypersensitive to mechanical stimulation. Immunohistochemical analysis revealed that IgG from FMS patients specifically labeled satellite glial cells and myelinated fibre tracts, as well as a small number of macrophages and endothelial cells in mouse dorsal root ganglia but not skin, muscle, spinal cord and brain. Our results demonstrate that fibromyalgia pain is caused by IgG autoantibodies that sensitize peripheral nociceptive afferents neurons and suggest that therapies that reduce patient IgG titres may be effective treatments of fibromyalgia pain.

neuroscience↗

bioRxiv2019

Effects of age, BMI and sex on the glial cell marker TSPO - a multicentre PBR28 HRRT PET study

PurposeTo investigate the effects of ageing, sex and body mass index (BMI) on translocator protein (TSPO) availability in healthy subjects using positron emission tomography (PET) and the radioligand [11C]PBR28. Methods[11C]PBR28 data from 140 healthy volunteers (72 males and 68 females; n=78 with HAB and n=62 MAB genotype; age range 19-80 years; BMI range 17.6 - 36.9) were acquired with High Resolution Research Tomograph at three centres: Karolinska Institutet (n=53), Turku PET centre (n=62) and Yale University PET Center (n=25). The total volume of distribution (VT) was estimated in global grey matter, frontal, temporal, occipital and parietal cortices, hippocampus and thalamus using multilinear analysis 1. The effects of age, BMI and sex on TSPO availability were investigated using linear mixed effects model, with TSPO genotype and PET centre specified as random intercepts. ResultsThere were significant positive correlations between age and VT in the frontal and temporal cortex. BMI showed a significant negative correlation with VT in all regions. Additionally, significant differences between males and females were observed in all regions, with females showing higher VT. A subgroup analysis revealed a positive correlation between VT and age in all regions in male subjects, whereas age showed no effect on TSPO levels in female subjects. ConclusionThese findings provide evidence that individual biological properties may contribute significantly to the high variation shown in TSPO binding estimates, and suggest that age, BMI and sex can be confounding factors in clinical studies.

immunology↗