Differences between serum polar lipid profiles of male and female rheumatoid arthritis patients in response to glucocorticoid treatment

Abstract

ObjectiveAs there are pharmacological differences between males and females, and glucocorticoid (GC) treatment is associated with increased cardiovascular mortality rate in rheumatoid arthritis (RA) patients, it is important to study serum polar lipid profiles of male and female patients in response to GC therapy. Gender differences may require an adjustment to the treatment strategy for a selection of patients.MethodsSerum samples from 281 RA patients were analysed using a targeted lipidomics platform. The differences in GC use and gender on polar lipid profiles were cross sectionally examined by multiple linear regressions, while correcting for confounding factors.ResultsDifferences in polar lipids between GC users and non-GC users in females and males were merely restricted to lysophospholipids (lysophosphatidylcholines and lysophosphatidylethanolamines). Lysophospholipids in female patients treated with GCs were significantly higher than female patients not treated with GCs (p = 6.0 E−6), whereas no significant difference was observed in male GC users versus non-users (p = 0.397).ConclusionThe lysophospholipid profiles in response to GCs were significantly different between male and female RA patients, which may have implications for the cardiovascular risk of GC treatment.Electronic supplementary materialThe online version of this article (doi:10.1007/s10787-016-0284-1) contains supplementary material, which is available to authorized users.

Circulating Pro- and Anti-Inflammatory Metabolites and Its Potential Role in Rheumatoid Arthritis Pathogenesis

“…Higher in women on GC: lysophosphatidylcholines and lysophosphatidylethanolamines. In men, lysophospholipids levels were similar between GC users and nonusers [7] Cross-sectional. RA…”

“…The study of these changes might help to understand RA pathogenesis, since the therapeutic effects of these drugs could potentially be driven by metabolic changes either by normalizing their abnormal values or by increasing anti-inflammatory metabolites. For instance, using a targeted metabolomic approach, Fu et al compared the effect of oral glucocorticoids (GC) on serum polar lipids and observed an increase in lysophosphatidylcholines (LPC) and lysophosphatidylethanolamines (LPE) in females but not in male patients with RA [7]. GC inhibits phospholipase A, a key enzyme that hydrolyzes membrane phospholipids which is increased in inflammatory tissues.…”

A Review of Metabolomic Profiling in Rheumatoid Arthritis: Bringing New Insights in Disease Pathogenesis, Treatment and Comorbidities

“…The effect of GC on phospholipase likely modifies the phospholipid profile and may be related to cardiovascular risks in RA [ 146 ]. Fu et al analyzed GC therapy on serum polar lipids and observed an increase in lysophosphatidylcholines (LPC) and lysophosphatidylethanolamine (LPE) in female RA patients [ 143 ]. Dimethylarginine levels were lower in patients on chronic GC use compared with non-glucocorticoids users, suggesting that long-term GC treatments improved endothelial function and induce cardiovascular protective effects by modulating arginine metabolism [ 143 ].…”

Changes in the Canine Plasma Lipidome after Short- and Long-Term Excess Glucocorticoid Exposure

“…Biological variability is expected within dog cohorts, which are usually more heterogeneous than, for example, mice cohorts. A sex-specific response to GC, affecting plasma lipids, have been observed in humans 28–30 . Each treatment group in our study included about two-thirds male and one-third female dogs.…”