P002/O26 Difference between palindromic rheumatism and early rheumatoid arthritis at the level of gene expression
Authors: S Ajaib, A Chapman, A Burska, K Mankia, P Emery, F Ponchel
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Career situation of first and presenting author</h3> Student for a master or a PhD. <h3>Introduction</h3> Palindromic rheumatism (PR) is characterised by recurrent, episodic attacks of articular inflammation, which resolve completely without residual joint damage. Whether PR should be considered as a prodrome of rheumatoid arthritis (RA) or as a distinct syndrome remains unclear, over 70 years since first described.<sup>1</sup> PR patients (non flare and during flare) were recruited in Leeds; RA and HC data was obtained from the RA-Map consortium. Differentially expressed genes (DEGs) were identified following a standard microarray analysis workflow. These findings reported the presence of distinct gene expression profiles within palindromic patients, compared to HC and those with drug naïve, early RA.<sup>2</sup> <h3>Objectives</h3> To validate a 10 gene signature as a discriminant between PR and RA in order to better classify patients suspected of having PR and to observe this signature as PR patients progress to early RA. <h3>Methods</h3> PBMCs were taken from non-flare PR (n=24); flare PR (n=16); PR progressors to RA (PR<b>→</b>RA, n=10); RA (n=16); and patients suspected of having PR without an official diagnosis (SpPR, n=31). All patients provided informed written consent. qPCR gene expression analysis was performed using 10 TaqMan assays and a house keeping gene. <h3>Results</h3> Functional analysis of the DEGs revealed significantly enriched gene pathways<sup>2</sup>, from which a group of 10 DEGs with high expression fold differences between PR and RA were selected and grouped into three signatures: PR signature (high RPL10, low IL10, CCR6, UBC, and SHCBP1); RA signature (high ALPL, JUN and IFTIM2); Non-Flare vs Flare signature (high EIF3E, low HSPA9). Comparing PR (non-flare and flare) with RA, 2 of the 5 genes (IL10, UBC) associated with PR were significantly different to RA (p&lt;0.05). For the RA signature, 2/3 genes (JUN and IFITM2) were expressed significantly higher in RA (p&lt;0.01). Comparing PR<b>→</b>RA with RA, we observe higher levels of expression for 3/10 genes (ALPL, CCR6, SHCBP1, p=0.05), and overall higher median values for 7 genes, not including IFITM2 and IL10 (suggesting non-RA). Finally, comparing SpPR to PR and RA groups, we observed little differences in gene expression with PR; suggesting a correct diagnosis as no patients displayed a signature resembling that of RA. Nevertheless, one gene (JUN) was significantly higher in SpPR compared with PR, suggesting these patients may be in a more progressed disease state when presenting at the clinic. <h3>Conclusions</h3> There are distinct differences (at the level of gene expression) between PR and RA, and those patients who progress to RA from PR display a molecular signature that remains closer to PR than RA. <h3>References</h3> Hench P, <i>et al. Arch Int Med</i> 1944;73:293–321. Ajaib S, <i>et al</i>. EWRR-2018. P090. <i>Annals of the Rheumatic Diseases</i> 2018;77:A51–A52. <h3>Disclosure of Interest</h3> None declared.