Background The interferon (IFN) signature has mainly been studied in established rheumatoid arthritis (RA), and was associated with poor response to rituximab. Serum levels of CCL2 (Monocyte Chemotactic Protein 1, MCP-1), CXCL10 (Interferon gamma –inducible 10 kDa Protein, IP-10) and CCL19 (Macrophage Inflammatory Protein 3 beta, MIP-3beta) are associated with an interferon (IFN) gene signature and disease activity in systemic lupus.
Objectives The objectives of the study were to assess the association between the IFN serum signature, disease activity, autoantibody secretion, radiographic progression and rapid initiation of a biologic DMARD in early RA.
Methods Serum levels of CCL2, CXCL10, and CCL19 were assessed in the ESPOIR cohort composed of 813 patients with early arthritis (more than 6 weeks and less than 6 months) not treated with steroid or DMARD. RA was defined according to ACR/EULAR 2010 criteria. An elevated level of each chemokine was defined as a value greater than the mean + 2DS value of the control population (88 sex and age-matched subjects). Patients with at least 2 out of 3 IFN-regulated chemokines were defined to have an IFN-high score.
Results Among the 813 patients included in the ESPOIR cohort, 641 patients had RA according to ACR/EULAR 2010 criteria. Elevated levels of CCL2, CXCL10, CCL19 were observed in 1.9% of early RA patients vs 0.6% of patients with other early arthritides (P=0.5), 49.4 vs 38.2% (P=0.01) and 23.3 vs 7.1% (P<0.0001), respectively. An IFN-high score was observed in 15.1% of RA patients vs 2.9% of patients with other early arthritides (P<0.0001).
Among the 641 patients with RA according to ACR/EULAR 2010 criteria, CXCL10 and CCL19 were significantly correlated with DAS28 at enrollment (r=0.22 and r=0.16, respectively,P<0.0001 for both) whereas CCL2 was not. Patients with RF or anti-CCP autoantibodies only had elevated levels of CCL19 (315.5[142.6-631.6] vs 214.4 [101.2-443.0] pg/ml, P<0.0001 and 332.6 [161.1-645.8] vs 214.5 [96.4-447.6] pg/ml, P<0.0001) whereas they had similar CCL2 and CXCL10 levels. RF and anti-CCP positivity were not associated with IFN-high score. Radiographic progression at 3 years (increase of total Sharp score greater than 5) was only associated with increased levels of CCL19 (P=0.05) but not with CCL2 or CXCL10, or with IFN-high score. Initiation of a biologic DMARD within the first year after enrollment was only significantly associated with increased levels of CCL19 (391.8 [197.3-548.6] vs 263.1[166.4-533.8] pg/ml, P=0.03).
Conclusions In early RA, serum CCL19 level is associated with disease activity, autoantibody secretion and 3-year radiographic progression. Patients with a high-IFN serum signature represent 15% of patients with early RA, with a rather good prognosis since high-IFN serum signature was not associated with autoantibody secretion, radiographic progression, or rapid initiation of a biologic DMARD treatment of RA.
Disclosure of Interest : None declared
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