Background Hepcidin is an interleukin 6-induced peptide hormone produced by the liver and involved in iron homeostasis and inflammation. Previous published studies have suggested that hepcidin could be a key biomarker of severity in rheumatoid arthritis (RA).
Objectives We investigated whether serum hepcidin level may represent a novel surrogate biomarker of RA features, disease activity, or of structural progression.
Methods Serum hepcidin level was assessed by enzyme immunoassay kit (Bachem, UK) in 791 patients from the French ESPOIR early arthritis cohort (at least 2 swollen joints for more than 6 weeks and less than 6 months) who met the 2010 EULAR-ACR criteria for RA (n=632) or had undifferentiated arthritis (UA) (n=159) at inclusion. We compared baseline hepcidin levels between RA and UA, searched for a cross-sectional association with the baseline clinical, immunological and radiological RA features, and determined, using univariate and multivariate analyses, whether log-transformed hepcidin level may predict the progression of X-ray alterations defined by an increase of the total Sharp/van der Heijde score ≥1.
Results Mean (±SD) level of hepcidin was higher in RA than in UA patients (53.02±48.45 vs 39.63±39.87 ng/mL, p<0.0001). In RA patients, serum hepcidin was higher when rheumatoid factor (RF) or anti-CCP were positive compared to their absence (57.5±51.6 vs 46.9±43.2 ng/mL, p=0.0007; 58.3±52.1 vs 47.8±44.0 ng/mL, p=0.0007, respectively). Correlation between hepcidin levels and DAS28 (r=0.1, p=0.01) was mainly explained by its correlation with erythrocyte sedimentation rate (ESR) (r=0.21, p<0.0001) and with C reactive protein (r=0.24, p<0.0001). A higher hepcidin concentration was significantly associated with an increased HAQ (r=0.14, p=0.0005), but not with fatigue level. Hepcidin level was unchanged whether anaemia was present or not (p=0.4), was not correlated with haemoglobin level but correlated with ferritinemia (r=0.27, p<0.0001). Baseline hepcidin level was higher in erosive compared with non erosive RA patients at inclusion (62.77±50.01 versus 51.01±47.93 ng/mL, p=0007). Log (hepcidin level) was associated with radiographic progression at 1 year (odds ratio=1.38 [95%CI:1.10-1.72]; p<0.0001) in the univariate but not in the multivariate analysis which included relevant confounders (gender, DAS28 at inclusion, HAQ level at inclusion, RF positivity, antiCCP antibodies positivity) (odds ratio=1.24 [95%CI:0.92-1.67]; p=0.16).
Conclusions Serum hepcidin level is elevated in RF/anti-CCP-positive RA patients and in erosive RA. Serum hepcidin increase reflects a higher disease activity and correlates with HAQ, suggesting a clinical relevance of its assessment beyond its link with the ESR. However, its measurement does not give additional information compared to the usual biomarkers of inflammation nor it predicts radiographic progression.
Disclosure of Interest None Declared
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