Background/Purpose:

Dickkopf-1 (DKK-1) is an inhibitory protein of the Wnt signalling pathway that could be involved in subchondral bone erosions occurring in rheumatoid arthritis (RA). Few studies have investigated the role of DKK1 in RA. We aimed to investigate DKK-1 serum levels in patients with recent inflammatory arthritis fulfilling ACR/EULAR criteria for RA and to investigate the parameters associated with DKK-1 increase and the relationship between DKK-1 levels and radiographic changes in RA.

Methods:

The ESPOIR cohort is a prospective, multicenter French cohort of patients with early arthritis, including 813 patients between 2002 and 2008. DKK-1 serum levels were assessed at baseline on the whole cohort by sandwich ELISA (Biomedica, Vienna). DDK-1 serum levels were further analyzed at inclusion in the subgroup of patients fulfilling ACR/EULAR criteria for RA after 2 years of follow-up (N=694; 85.3%) and compared with serum levels from 70 age and sex-matched controls (without autoimmune or chronic inflammatory disease). Uni and multivariate analyses were conducted to look for parameters associated or correlated with DKK-1 serum levels. DKK-1 serum levels were also compared between patients with and without radiographic change at baseline and after 2 years of follow-up.

Results:

Among the 813 patients with early arthritis, 694 of them (85%) fulfilled ACR/EULAR criteria for RA (mean age 48.5±12.3, 78.2% female, with mean baseline DAS28=5.3±1.2, 54.6% anti-CCP positive). Serum DKK-1 level was significantly increased in RA patients compared to healthy controls (28.0±13.2 vs 10.8±9.3; p<0.0001). In univariate analysis, the level of DDK-1 was significantly correlated with the level of CRP (r=0.16; p<0.0001), ESR (r=0.11; p=0.005), patient global assessment (PGA) (r=0.08; p=0.046) and DAS28 (r=0.09; p=0.02). In addition, we found that DKK-1 level was significantly higher in patients with typical erosion related to RA at baseline, compared to those without (32.4±14.0 vs 27.2±12.9; p=0.0001). In the multivariate analysis adjusted for DAS28, PGA, and smoking status, only CRP levels and the presence of typical erosions related to RA remained associated with DKK-1 levels. Last, the most interesting result was that baseline DKK-1 levels was predictive of radiological progression (defined by increase of modified Sharp score >1) (29.3±13.0 in patients with progression vs 16.7±12.1 in patients without progression; p=0.025). Nevertheless, DKK-1 was no more associated with radiological progression in a model including other main predictors of severity (erosion at baseline, and anti-CCP positivity) in the multivariate analysis.

Conclusion:

This study conducted in a large cohort of patients presenting with early onset RA clearly showed an increase in DKK-1 serum levels, associated with disease activity, biological inflammation and bone erosions at baseline. More interestingly, increase in DKK-1 serum levels were predictive of structural progression at 2 years and, then might be an interesting new structural biomarker in early RA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/dickkopf-1-is-increased-in-rheumatoid-arthritis-of-recent-onset-and-might-be-a-new-biomarker-of-structural-progression-data-from-the-espoir-cohort/