Genomic stratification by expression of HLA-DRB4 alleles identifies differential innate and adaptive immune transcriptional patterns - A strategy to detect predictors of methotrexate response in early rheumatoid arthritis

Genomic stratification by expression of HLA-DRB4 alleles identifies differential innate and adaptive immune transcriptional patterns - A strategy to detect predictors of methotrexate response in early rheumatoid arthritis

Copyright © 2016 Elsevier Inc. All rights reserved.

Bibliographische Detailangaben
Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 171(2016) vom: 15. Okt., Seite 50-61
1. Verfasser: Stuhlmüller, Bruno (VerfasserIn)
Weitere Verfasser: Mans, Karsten, Tandon, Neeraj, Bonin, Marc O, Smiljanovic, Biljana, Sörensen, Till A, Schendel, Pascal, Martus, Peter, Listing, Joachim, Detert, Jacqueline, Backhaus, Marina, Neumann, Thomas, Winchester, Robert J, Burmester, Gerd-R, Häupl, Thomas
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2016
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Journal Article Genetics Innate and adaptive immunity Methotrexate Response prediction Rheumatoid arthritis Antirheumatic Agents HLA-DRB4 Chains YL5FZ2Y5U1
Beschreibung
Zusammenfassung:Copyright © 2016 Elsevier Inc. All rights reserved.
Effective drug selection is the current challenge in rheumatoid arthritis (RA). Treatment failure may follow different pathomechanisms and therefore require investigation of molecularly defined subgroups. In this exploratory study, whole blood transcriptomes of 68 treatment-naïve early RA patients were analyzed before initiating MTX. Subgroups were defined by serologic and genetic markers. Response related signatures were interpreted using reference transcriptomes of various cell types, cytokine stimulated conditions and bone marrow precursors. HLA-DRB4-negative patients exhibited most distinctive transcriptional differences. Preponderance of transcripts associated with phagocytes and bone marrow activation indicated response and transcripts of T- and B-lymphocytes non-response. HLA-DRB4-positive patients were more heterogeneous, but also linked failure to increased adaptive immune response. RT-qPCR confirmed reliable candidate selection and independent samples of responders and non-responders the functional patterning. In summary, genomic stratification identified different molecular pathomechanisms in early RA and preponderance of innate but not adaptive immune activation suggested response to MTX therapy
Beschreibung:Date Completed 31.05.2017
Date Revised 31.05.2017
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-7035
DOI:10.1016/j.clim.2016.08.013