Diffusion tensor imaging analysis of rheumatoid arthritis patients with neuropsychiatric features to determine the alteration of white matter integrity due to vascular events

Phukan, Pranjal; Barman, Bhupen; Chengappa, Nivedita Kharkongor; Lynser, Donboklang; Paul, Subhraneel; Nune, Arvind; Sarma, Kalyan

doi:10.1007/s10067-022-06262-4

Cited by 6 publications

(4 citation statements)

References 30 publications

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“…It has also been reported that mast cells can release the content of individual secretory granules [71] or individual mediators without degranulation [52]. This process was distinct from "piecemeal degranulation" [72], granule-associated vesicle transport [63] or the release of extracellular vesicles [67,[73][74][75][76][77][78]. Moreover, mast cell mediators could have autocrine actions affecting the expression of receptors or the overall reactivity of mast cells.…”

Section: Mast Cell Mediators and Mechanisms Of Secretionmentioning

confidence: 99%

Potential Role of Moesin in Regulating Mast Cell Secretion

Kempuraj

2023

IJMS

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Mast cells have existed for millions of years in species that never suffer from allergic reactions. Hence, in addition to allergies, mast cells can play a critical role in homeostasis and inflammation via secretion of numerous vasoactive, pro-inflammatory and neuro-sensitizing mediators. Secretion may utilize different modes that involve the cytoskeleton, but our understanding of the molecular mechanisms regulating secretion is still not well understood. The Ezrin/Radixin/Moesin (ERM) family of proteins is involved in linking cell surface-initiated signaling to the actin cytoskeleton. However, how ERMs may regulate secretion from mast cells is still poorly understood. ERMs contain two functional domains connected through a long α-helix region, the N-terminal FERM (band 4.1 protein-ERM) domain and the C-terminal ERM association domain (C-ERMAD). The FERM domain and the C-ERMAD can bind to each other in a head-to-tail manner, leading to a closed/inactive conformation. Typically, phosphorylation on the C-terminus Thr has been associated with the activation of ERMs, including secretion from macrophages and platelets. It has previously been shown that the ability of the so-called mast cell “stabilizer” disodium cromoglycate (cromolyn) to inhibit secretion from rat mast cells closely paralleled the phosphorylation of a 78 kDa protein, which was subsequently shown to be moesin, a member of ERMs. Interestingly, the phosphorylation of moesin during the inhibition of mast cell secretion was on the N-terminal Ser56/74 and Thr66 residues. This phosphorylation pattern could lock moesin in its inactive state and render it inaccessible to binding to the Soluble NSF attachment protein receptors (SNAREs) and synaptosomal-associated proteins (SNAPs) critical for exocytosis. Using confocal microscopic imaging, we showed moesin was found to colocalize with actin and cluster around secretory granules during inhibition of secretion. In conclusion, the phosphorylation pattern and localization of moesin may be important in the regulation of mast cell secretion and could be targeted for the development of effective inhibitors of secretion of allergic and inflammatory mediators from mast cells.

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Section: Mast Cell Mediators and Mechanisms Of Secretionmentioning

confidence: 99%

Potential Role of Moesin in Regulating Mast Cell Secretion

Kempuraj

2023

IJMS

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“…Those that presented with WMH had higher serum levels of the S100B protein, a marker of inflammation and neurodegeneration and were also more likely to perform more poorly on cognitive tests (Hamed et al, 2012). In RA patients with neuropsychiatric symptoms in particular, there was an increased diffusion coefficient and radial diffusivity (p<0.05) and a decreased fractional anisotropy coefficient and axial diffusivity (p<0.05), indicative of less healthy white matter (Phukan et al, 2022). The authors suggest that this could be due to the central nervous system vasculitis that is sometimes present in RA which can result in tissue hypoxia, disruption of the blood-brain barrier and ultimately degeneration of axons, neuronal cells, and the myelin in the white matter fibers.…”

Section: Introductionmentioning

confidence: 99%

“…A few studies (N<60) that investigated cross-sectionally whether there are any central nervous system differences in RA, found cerebral hyperintense lesions as well as altered white matter integrity in their RA subsample compared to the healthy control group (Hamed et al, 2012;Phukan et al, 2022). Those that presented with WMH had higher serum levels of the S100B protein, a marker of inflammation and neurodegeneration and were also more likely to perform more poorly on cognitive tests (Hamed et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Associations between self-reported rheumatoid arthritis, rheumatoid factor positivity and structural brain phenotypes in the UK Biobank

Stanciu¹,

Lyall²,

Siebert³

et al. 2022

Preprint

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Objectives: The literature on structural brain health in people with rheumatoid arthritis (RA) is very limited. Our aim was to investigate whether there are any brain phenotype differences between people that are positive rheumatoid factor (RF+) and/or people that self-reported RA, compared with people who are not RF+ and do not report RA (‘healthy controls’). Methods: We tested for cross-sectional associations between RA and/or RF+ vs. several MRI brain volume variables in the UK Biobank (n=37, 379 participants, out of which 432 reported RA and 1,833 were RF+). We adjusted for age, sex, and assessment centre in the partially adjusted models, while in the fully adjusted models we additionally controlled for deprivation, smoking and cardiometabolic conditions. Results: Those that self-reported RA were more likely to have increased log white matter hyperintensity volumes (WMH standardised β= 0.08, 95% CI= 0.021; 0.14, p<0.01), and smaller volumes of the amygdala (β=-0.09, 95% CI= -0.16; -0.02, p<0.01) in the partially adjusted analyses. In the fully adjusted model RA remained significantly associated with amygdala volume (β=-0.09, 95% CI= -0.16; -0.02, p<0.01). No significant associations with RF+ status were found. Conclusion: Our study provides evidence for differences in structural brain volumes that are known to be related to psychological and cognitive health in those with vs. without RA. Since previous literature suggests a potential role for the amygdala in pain modulation and mental health, and an increased risk for stroke associated with WMH, we believe that our findings may be of clinical importance to people with RA. Further research is necessary to confirm these associations and asses their functional implications.

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“…They are indicative of changes in white matter fibers and tracts [9]. There are several studies that look specifically at brain white matter in both RA and UC [10, 11]. However, the literature around white matter hyperintensities has been conflicting.…”

Section: Introductionmentioning

confidence: 99%

Volume and Distribution of White Matter Hyperintensities in Rheumatoid Arthritis and Ulcerative Colitis Patients

Cox,

Cole,

Kempton

et al. 2024

Preprint

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Brain white matter disruptions have been implicated in contributing to fatigue, brain fog and other central symptoms commonly reported in inflammatory diseases. In this study, we included 252 RA patients with 756 age and sex matched controls and 240 UC patients with 720 age and sex matched controls using the UK Biobank imaging dataset. We looked for differences in total volume of white matter hyperintensities (WMH) between patients compared to controls. Then, using voxelwise analysis, we explored the spatial distribution of these white matter hyperintensities and differences in these between patients and controls and between disease groups.A significantly higher volume of WMH was observed in both the RA (p = 2.0 x 10-8, β = - 0.36, 95% CI = -0.48, -0.23) and UC (p = 0.003, β = -0.19 95% CI = -0.32, -0.07) patients compared to their respective control groups. Voxelwise analysis revealed only a small cluster of RA associated WMH compared to controls.These results indicate an increased risk of white matter hyperintensities in patients with RA and UC. These findings help quantify the effect of inflammation from autoimmune diseases on cerebrovascular health and white matter integrity.

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Diffusion tensor imaging analysis of rheumatoid arthritis patients with neuropsychiatric features to determine the alteration of white matter integrity due to vascular events

Cited by 6 publications

References 30 publications

Potential Role of Moesin in Regulating Mast Cell Secretion

Potential Role of Moesin in Regulating Mast Cell Secretion

Associations between self-reported rheumatoid arthritis, rheumatoid factor positivity and structural brain phenotypes in the UK Biobank

Volume and Distribution of White Matter Hyperintensities in Rheumatoid Arthritis and Ulcerative Colitis Patients

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