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In haemophilia, the recurrence of hemarthrosis leads to irreversible arthropathy termed haemophilic arthropathy (HA). However, HA is a unique form of arthropathy in which resident cells, such as fibroblast‐like synoviocytes (FLS), come into direct contact with blood. Therefore, we hypothesized that FLS in HA could have a unique inflammatory signature as a consequence of their contact with blood. We demonstrated with ELISA and ELISPOT analyses that HA‐FLS expressed a unique profile of cytokine secretion, which differed from that of non‐HA‐FLS, mainly consisting of cytokines involved in innate immunity. We showed that unstable cytokine mRNAs were involved in this process, especially through miRNA complexes as confirmed by DICER silencing. A miRNOME analysis revealed that 30 miRNAs were expressed differently between HA and non‐HA‐FLS, with most miRNAs involved in inflammatory control pathways or described in certain inflammatory diseases, such as rheumatoid arthritis or lupus. Analysis of transcriptomic networks, impacted by these miRNAs, revealed that protein processes and inflammatory pathways were particularly targeted in LPS‐induced FLS, and in particular vascularization and osteoarticular modulation pathways in steady‐state FLS. Our study demonstrates that the presence of blood in contact with FLS may induce durable miRNA changes that likely participate in HA pathophysiology.

A 52-year-old woman with no medical history was admitted on March 18, 2020, presenting since 3 days asthenia, abdominal pain, and dry cough but no fever. Adenomegalies, splenomegaly, leukocytosis, and elevated LDH suggested mature lymphoproliferation. Considering the current health context, an RT-PCR testing for COVID-19 (coronavirus disease 2019) was performed and found to be positive. Early chest CT showed no sign of pulmonary infection but multiple adenomegalies. An 18F-FDG PET/CT performed 5 days later to assess the extent of the hemopathy revealed the apparition of FDG-avid bilateral ground glass and subpleural curvilinear opacities suggesting COVID-19–associated pneumopathy.