Increased monohexosylceramide levels in the serum of established rheumatoid arthritis patients

Abstract

Objectives To identify serum sphingolipids that could act as candidate biomarkers in RA. Methods We performed lipidomic analyses in the serum of 82 participants: 19 established RA patients, 18 untreated early RA patients, 13 untreated early arthritis patients not fulfilling the classification criteria for RA, 12 established SpA patients and 20 controls. We compared the lipid levels from the different patient groups with the control group through multiple-regression analyses controlling for age at diagnosis, gender and medication (cDMARDs and corticoids). Results Established RA patients had significantly increased levels of sphingosine, monohexosylceramide and ceramide compared with controls, when controlling for age and gender. Monohexosylceramide levels remained significantly increased when additionally controlling for medication. On the contrary, SpA patients had significantly decreased levels of ceramide, in both analyses. Conclusion We observed a detectable increase in the levels of certain sphingolipids in the serum of established RA patients when compared with controls, in line with previous observations in the synovial fluid. Such findings provide further evidence that sphingolipids may play a key role in the pathophysiology of RA.

Uncovering Mechanisms of Zanthoxylum piperitum Fruits for the Alleviation of Rheumatoid Arthritis Based on Network Pharmacology

“…Prolactin signaling pathway: Prolactin collaborates with other proinflammatory factors to stimulate macrophages through prolactin receptors which might be a potential therapeutic target in RA [ 35 ]. Sphingolipid signaling pathway: Sphingolipid expression level in RA elevated in the serum sample, consistent with known roles of sphingolipids related to inflammation [ 36 ]. Cyclic AMP (cAMP) signaling pathway: stimuli-induced cAMP production can exert proinflammatory effects in RA [ 37 ].…”

Multi-Omics Analysis of Microglial Extracellular Vesicles From Human Alzheimer’s Disease Brain Tissue Reveals Disease-Associated Signatures

“…An increase of this species of BMP, a lysosome-specific lipid, suggests increased lysosomal lipid content in AD microglia ( Showalter, et al, 2020 ). Elevated levels of MhCer may play a role in microglial activation and immune response ( Brennan, et al, 2017 ; Miltenberger-Miltenyi, et al, 2020 ; Niimura et al, 2010 ), as well as be a precursor of more complex gangliosides ( Merrill, 2011 ). Interestingly, enrichment of BMP and MhCer in EVs has been previously linked to the impairment of endolysosomal function induced by Vsp34 kinase inhibition, which causes phosphatidylinositol-3-phosphate (PI3P) deficiency ( Miranda, et al, 2018 ).…”

Altered Serum Phospholipids in Atopic Dermatitis and Association with Clinical Status

“…Serum levels of Sph are associated with the symptomatic phenotypes of patients with COVID-19 ( Janneh et al., 2021 ) and are fluctuated in patients with hepatitis B virus or hepatitis C virus by virologic conditions ( Grammatikos et al., 2016 ; Mücke et al., 2018 ). In patients with rheumatoid arthritis, serum Sph and Cer levels are increased ( Miltenberger-Miltenyi et al., 2020 ), and the PC/LPC ratios of plasma represent a measure of inflammation ( Fuchs et al., 2005 ). PC has been reported as a factor related to the effect of omalizumab in AD ( Hotze et al., 2014 ), suggesting the association between increased serum Sph and PC (and S1P) levels and inflammation in AD.…”