Year-end Sale % OFF 
Abstract
IntroductionGenetic and disease-related factors give rise to a wide spectrum of glucocorticoid (GC) sensitivity in rheumatoid arthritis (RA). In clinical practice, GC treatment is not adapted to these differences in GC sensitivity. In vitro assessment of GC sensitivity before the start of therapy could allow more individualized GC therapy. The aim of the study was to investigate the association between in vitro and in vivo GC sensitivity in RA.MethodsThirty-eight early and 37 established RA patients were prospectively studied. In vitro GC sensitivity was assessed with dexamethasone-induced effects on interleukin-2 (IL-2) and glucocorticoid-induced leucine zipper (GILZ) messenger RNA expression in peripheral blood mononuclear cells (PBMCs). A whole-cell dexamethasone-binding assay was used to measure number and affinity (1/KD) of glucocorticoid receptors (GRs).In vivo GC sensitivity was determined by measuring the disease activity score (DAS) and health assessment questionnaire disability index (HAQ-DI) score before and after 2 weeks of standardized GC treatment.ResultsGR number was positively correlated with improvement in DAS. IL-2-EC50 and GILZ-EC50 values both had weak near-significant correlations with clinical improvement in DAS in intramuscularly treated patients only. HAQ responders had lower GILZ-EC50 values and higher GR number and KD.ConclusionsBaseline cellular in vitro glucocorticoid sensitivity is modestly associated with in vivo improvement in DAS and HAQ-DI score after GC bridging therapy in RA. Further studies are needed to evaluate whether in vitro GC sensitivity may support the development of tailor-made GC therapy in RA.
Highlights
Genetic and disease-related factors give rise to a wide spectrum of glucocorticoid (GC) sensitivity in rheumatoid arthritis (RA)
Assessment of in vitro glucocorticoid sensitivity In the treatment in the Rotterdam early arthritis cohort (tREACH) cohort, in vitro GC sensitivity was assessed with the GC bioassays
The only study with longitudinal data on glucocorticoid receptor (GR) expression in RA reports an increase in GR expression over time in female RA patients, suggesting a compensatory mechanism for the ongoing inflammatory state [11]. In addition to this concept, the higher numbers of GRs in our cohort might be interpreted as a counterbalancing mechanism for the reduced GC sensitivity. In line with this hypothesis, we found a correlation between higher numbers of GRs and lower half-maximal effective concentration (EC50) values of glucocorticoid-induced leucine zipper (GILZ) and IL-2
Summary
Genetic and disease-related factors give rise to a wide spectrum of glucocorticoid (GC) sensitivity in rheumatoid arthritis (RA). Rheumatoid arthritis (RA) is a common autoimmune disorder characterized by chronic synovial inflammation, leading to joint destructions. Based on their antiinflammatory properties, glucocorticoids (GCs) have an important role in first-line treatment regimens for RA in combination with disease-modifying antirheumatic drugs (DMARDs). Determinants of individual GC sensitivity include both genetic and acquired factors. Acquired, diseaserelated factors include the effects of inflammation, mediated by proinflammatory cytokines, on cellular GC sensitivity, resulting in systemic or tissue-specific GC resistance of immunocompetent cells at the site of inflammation [6]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
