Cytokine and chemokine gene expression in patients with clinically suspect arthralgia; a longitudinal study during progression to inflammatory arthritis or non-progression

BackgroundAutoantibody-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 can also rise years before IA-onset, but the course after CSA-onset is unknown. To better understand the processes in this symptomatic at-risk phase, 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. Differential expressed genes between ACPA-positive and ACPA-negative CSA-patients who developed IA were also explored. MethodsWhole blood RNA expression of 37 inflammatory cytokines/chemokines/related receptors was determined by dual-color 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. GEE-models tested changes over time. A false discovery rate approach was applied to correct for multiple testing. ResultsNone 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 TNIP expression increased (p<0.001 and p=0.002, respectively) over a 2-year period. Expression levels in ACPA-positive and ACPA-negative CSA-patients who developed IA were similar. ConclusionWhole blood gene expression of cytokines, chemokines and related receptors did not change significantly from CSA to IA-development. This suggests that changes in expression of these molecules occurred preceding CSA-onset and may not relate to the final hit of developing chronic arthritis. Observed changes in CSA-patients not developing IA can provide clues for processes related to resolution.