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  3. Predicting glucocorticoid resistance in multiple sclerosis relapse via a whole blood transcriptomic analysis.
 

Predicting glucocorticoid resistance in multiple sclerosis relapse via a whole blood transcriptomic analysis.

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BORIS DOI
10.48350/187101
Publisher DOI
10.1111/cns.14484
PubMed ID
37817393
Description
AIMS

Treatment of multiple sclerosis (MS) relapses consists of short-term administration of high-dose glucocorticoids (GCs). However, over 40% of patients show an insufficient response to GC treatment. We aimed to develop a predictive model for such GC resistance.

METHODS

We performed a receiver operating characteristic (ROC) curve analysis following the transcriptomic assay of whole blood samples from stable, relapsing GC-sensitive and relapsing GC-resistant patients with MS in two different European centers.

RESULTS

We identified 12 genes being regulated during a relapse and differentially expressed between GC-sensitive and GC-resistant patients with MS. Using these genes, we defined a statistical model to predict GC resistance with an area under the curve (AUC) of the ROC analysis of 0.913. Furthermore, we observed that relapsing GC-resistant patients with MS have decreased GR, DUSP1, and TSC22D3 mRNA levels compared with relapsing GC-sensitive patients with MS. Finally, we showed that the transcriptome of relapsing GC-resistant patients with MS resembles those of stable patients with MS.

CONCLUSION

Predicting GC resistance would allow patients to benefit from prompt initiation of an alternative relapse treatment leading to increased treatment efficacy. Thus, we think our model could contribute to reducing disability development in people with MS.
Date of Publication
2024-02
Publication Type
Article
Subject(s)
600 Technology > 610 Medicine & health
Keyword(s)
glucocorticoid glucocorticoid receptor multiple sclerosis resistance
Language(s)
en
Contributor(s)
Bagnoud, Maud Marie
Department for BioMedical Research, Forschungsgruppe Neurologie
Universitätsklinik für Neurologie
Remlinger, Jana Silkeorcid-logo
Department for BioMedical Research, Forschungsgruppe Neurologie
Universitätsklinik für Neurologie
Joly, Sandrine Marina Aline
Universitätsklinik für Neurologie
Massy, Marine
Salmen, Anke
Department for BioMedical Research, Forschungsgruppe Neurologie
Universitätsklinik für Neurologie
Chan, Andrew Hao-Kuang
Universitätsklinik für Neurologie - Neuroimmunologie
Department for BioMedical Research, Forschungsgruppe Neurologie
Karathanassis, Dimitris
Evangelopoulos, Maria-Eleptheria
Hoepner, Robert
Universitätsklinik für Neurologie
Department for BioMedical Research, Forschungsgruppe Neurologie
Additional Credits
Universitätsklinik für Neurologie
Department for BioMedical Research, Forschungsgruppe Neurologie
Universitätsklinik für Neurologie - Neuroimmunologie
Series
CNS neuroscience & therapeutics
Publisher
Wiley
ISSN
1755-5949
Access(Rights)
open.access
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