Arthritis is a joint inflammation associated with chronic autoimmune rheumatism such as rheumatoid arthritis (RA) and psoriatic arthritis (PsA). The most common form, RA, is characterized by synovial inflammation, cartilage and bone destruction. Recently, several studies have identified the involvement of local extra-hepatic hepcidin production in several inflammatory phenomena. However, how local hepcidin influences articular physiology and contributes to arthritis is poorly understood.

Our aim was to explore the local articular production of hepcidin and to evaluate its role in RA and PsA.

Using a cohort of arthritis patients, we measured (LC/MS/MS) higher levels of hepcidin in arthritis synovium, compared to osteoarthritis controls. To confirm a local articular production, we isolated mononuclear cells from arthritis synovial fluids and showed (RT-qPCR) that leucocytes expressed hepcidin mRNA. To recapitulate the conditions of inflammatory synovial infiltrate, we stimulated ex-vivo peripheral blood mononuclear cells with synovial fluids and showed that only inflammatory synovial fluids triggered hepcidin production. IL-6, a well-known pro-inflammatory cytokine in arthritis, is the major regulator of hepcidin in inflammatory conditions. Hepcidin induction by synovial fluids was only partially inhibited with IL-6R inhibitor but totally repressed with Filgotinib, a JAK inhibitor, suggesting additional factors to stimulate articular hepcidin in arthritis. Futures omics analyses will determine the regulatory pathways of hepcidin and iron metabolism in arthritis.

Our study strongly suggests that hepcidin production takes place locally in the joint under inflammatory arthritis, providing a state of the art for exploring the involvement of hepcidin and iron in the pathophysiology of RA and PsA.