Expression of Cytokine and Chemokine Genes in Patients with Clinically Suspect Arthralgia; A Longitudinal Study During Progression to Inflammatory Arthritis or Non-Progression

Judith Heutz¹, Cleo Rogier², Ellis Niemantsverdriet³, Susan van den Eeden⁴, Pascal de Jong⁵, Annemieke Geluk⁶ and Annette van der Helm-van Mil⁷, ¹Erasmus Medical Center, Rotterdam, Netherlands, ²Erasmus MC, Rotterdam, Netherlands, ³LUMC, Leiden, Netherlands, ⁴Leiden University Medical Center (LUMC), Leiden, Netherlands, ⁵ErasmusMC, Hendrik Ido Ambacht, Netherlands, ⁶Leiden University Medical Center (LUMC), Leiden, Zuid-Holland, Netherlands, ⁷Leiden University Medical Center, Erasmus Medical Center, Leiden, Netherlands

Meeting: ACR Convergence 2022

Keywords: chemokines, cytokines, Gene Expression, rheumatoid arthritis

Session Information

Date: Saturday, November 12, 2022

Title: RA – Diagnosis, Manifestations, and Outcomes Poster I

Session Type: Poster Session A

Session Time: 1:00PM-3:00PM

Background/Purpose: Autoantibody responses rise years before onset of inflammatory arthritis (IA) and are stable during transitioning from clinically suspect arthralgia (CSA) to IA (1). Cytokine and chemokine levels can also rise years before IA-onset, whilst CSA generally develops 6-12 months prior to IA-onset (2). Since the course of cytokines/chemokines in CSA is unknown, we studied the course of cytokine and chemokine 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 explored.

Methods: Whole blood RNA expression of 37 candidate inflammatory cytokines and chemokines was determined by dual-color reverse-transcription multiplex ligation-dependent probe amplification (dcRT-MLPA), in paired samples of CSA-patients at CSA-onset and either at IA-development or after 24-months without progression. ACPA-positive and ACPA-negative CSA-patients developing IA were compared at CSA-onset and during progression. GEE-models tested changes over time. A false discovery rate approach was applied to correct for multiple testing.

Results: In CSA-patients who progressed to IA, gene expression of none of the cytokines and chemokines significantly changed between CSA-onset and IA-development (Figure 1). In CSA-patients who did not progress to IA, G-CSF expression decreased (p=0.001) and CCR6 and TNIP expression increased (p< 0.001 and p=0.002, respectively) in 2-years (Figure 2). Gene expression levels in ACPA-positive and ACPA-negative CSA-patients who developed IA were similar.

Conclusion: Whole blood cytokine and chemokine gene expression did not change significantly over time from CSA to IA-development. This suggests that changes in systemic expression occurred preceding CSA-onset and may not relate to the final hit of developing chronic disease. Observed changes in CSA patients not developing IA can provide clues for processes related to resolution.

References
1. Wouters F et al. Ann Rheum Dis. 2020;80(4):540-2
2. Sokolove J et al. PLos One 2012;7(5):e35296

Figure 1. Modelled course of gene expression of 37 cytokines and chemokines in CSA patients who progressed to arthritis. Cytokines and chemokines were measured at baseline and at time of IA development. CSA, clinical suspect arthralgia; IA, inflammatory arthritis

Figure 2. Modelled course of gene expression of G-CSF, CCR6 and TNIP1 in CSA patients who did not progress to arthritis and patients that did progress to arthritis. Cytokines and chemokines were measured at baseline and after 2 years. CSA, clinical suspect arthralgia

Disclosures: J. Heutz, None; C. Rogier, None; E. Niemantsverdriet, None; S. van den Eeden, None; P. de Jong, None; A. Geluk, None; A. van der Helm-van Mil, None.

To cite this abstract in AMA style:

Heutz J, Rogier C, Niemantsverdriet E, van den Eeden S, de Jong P, Geluk A, van der Helm-van Mil A. Expression of Cytokine and Chemokine Genes in Patients with Clinically Suspect Arthralgia; A Longitudinal Study During Progression to Inflammatory Arthritis or Non-Progression [abstract]. Arthritis Rheumatol. 2022; 74 (suppl 9). https://acrabstracts.org/abstract/expression-of-cytokine-and-chemokine-genes-in-patients-with-clinically-suspect-arthralgia-a-longitudinal-study-during-progression-to-inflammatory-arthritis-or-non-progression/. Accessed .

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