Identification of biological pathways specific to phases preceding rheumatoid arthritis development through gene expression profiling.

Publisher: Blackwell Pub Country of Publication: England NLM ID: 101232337 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1744-313X (Electronic) Linking ISSN: 17443121 NLM ISO Abbreviation: Int J Immunogenet Subsets: MEDLINE

Original Publication: Oxford, UK : Blackwell Pub., c2005-

Arthritis, Rheumatoid/*immunology ; Autoantibodies/*genetics ; Biosynthetic Pathways/*genetics ; HLA-DRB1 Chains/*genetics; Adult ; Arthritis, Rheumatoid/genetics ; Arthritis, Rheumatoid/pathology ; Autoantibodies/immunology ; Biosynthetic Pathways/immunology ; Female ; Gene Expression Profiling ; HLA-DRB1 Chains/immunology ; Humans ; Male ; Middle Aged ; Transcriptome/genetics ; Transcriptome/immunology

The etiopathogenesis of rheumatoid arthritis is partially understood; however, it is believed to result from a multi-step process. The immune onset followed by pre-clinical phases will eventually lead to the development of symptomatic disease. We aim at identifying differentially expressed genes in order to highlight pathways involved in the pre-clinical stages of rheumatoid arthritis development. The study population consisted of first-degree relatives of patients with rheumatoid arthritis, known to have an increased risk of developing disease as compared to the general population. Whole transcriptome analysis was performed in four groups: asymptomatic without autoantibodies or symptoms associated with possible rheumatoid arthritis (controls); having either clinically suspect arthralgias, undifferentiated arthritis or autoimmunity associated with RA (pre-clinical stages of RA: Pcs-RA); having subsequently developed classifiable RA (pre-RA); and early untreated rheumatoid arthritis patients (RA). Differentially expressed genes were determined, and enrichment analysis was performed. Functional enrichment analysis revealed 31 pathways significantly enriched in differentially expressed genes for Pcs-RA, pre-RA and RA compared to the controls. Osteoclast pathway is among the seven pathways specific for RA. In Pcs-RA and in pre-RA, several enriched pathways include TP53 gene connections, such as P53 and Wnt signalling pathways. Analysis of whole transcriptome for phenotypes related to rheumatoid arthritis allows highlighting which pathways are requested in the pre-clinical stages of disease development. After validation in replication studies, molecules belonging to some of these pathways could be used to identify new specific biomarkers for individuals with impending rheumatoid arthritis.
(© 2021 John Wiley & Sons Ltd.)

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3200BO_120639 Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung

Keywords: Gene expression profiling; Rheumatoid arthritis development; Transcriptome

0 (Autoantibodies)
0 (HLA-DRB1 Chains)

Date Created: 20210122 Date Completed: 20210819 Latest Revision: 20210819

20240513

10.1111/iji.12528

33480472