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

Objectives Autoantibody-responses rise years before onset of inflammatory arthritis (IA) and are stable during transitioning from clinically suspect arthralgia (CSA) to IA. Cytokine and chemokine levels also rise years before IA-onset. However, the course in the at-risk stage of CSA during progression to disease or non-progression is unknown. To increase understanding of processes mediating disease development, we studied the course of cytokine, chemokine and related receptors gene expression in CSA-patients during progression to IA, and in CSA-patients who ultimately did not develop IA. Methods Whole-blood RNA-expression of 37 inflammatory cytokines/chemokines/related receptors was determined by dual-colour reverse-transcription multiplex ligation-dependent probe amplification, in paired samples of CSA-patients at CSA-onset and either at IA-development or after 24-months without IA-development. ACPA-positive and ACPA-negative CSA-patients developing IA were compared at CSA-onset and during progression to IA. Generalised estimating equations tested changes over time. A false discovery rate approach was applied. Results None of the cytokines/chemokine genes significantly changed in expression between CSA-onset and IA-development. In CSA-patients without IA-development, G-CSF expression decreased (p= 0.001), whereas CCR6 and TNIP1 expression increased (p< 0.001, p= 0.002, respectively) over a 2-year period. Expression levels in ACPA-positive and ACPA-negative CSA-patients who developed IA were similar. Conclusion Whole-blood gene expression of assessed cytokines/chemokines/related receptors did not change significantly from CSA to IA-development. This suggests that changes in expression of these molecules may not be related to the final process of developing chronicity and may have occurred preceding CSA-onset. Changes in gene expression in CSA-patients without IA-development may provide clues for processes related to resolution.

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The course of cytokine and chemokine gene expression in clinically suspect arthralgia patients during progression to inflammatory arthritis

Heutz

Niemantsverdriet

Eeden

et al. 2023

Rheumatology

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

Abstract: 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

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The course of cytokine and chemokine gene expression in clinically suspect arthralgia patients during progression to inflammatory arthritis

The course of cytokine and chemokine gene expression in clinically suspect arthralgia patients during progression to inflammatory arthritis

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