Exploring the association between circulating endothelial protein C receptor and disease activity of rheumatoid arthritis in a pilot study

Objectives: To investigate whether circulating endothelial protein C receptor (EPCR) is associated with disease activity and inflammatory markers in rheumatoid arthritis. Methods: Thirty-eight RA patients and 21 healthy controls (HC) were recruited via the A3BC biobank. Peripheral blood mononuclear cells and plasma were isolated from the blood of these participants. Plasma soluble (s)EPCR, IL-6, IL-17 and sCD14 were measured by enzyme-linked immunosorbent assay, cell membrane-associated (m)EPCR by flow cytometry; EPCR gene H3 single nucleotide polymorphism (SNP), which contributes to high plasma sEPCR levels, by PCR and DNA sequencing. Data were analysed using FlowJo10 and GraphPad Prism 10. Results: RA patients had higher levels of mEPCR on T cells and plasma sEPCR compared with HC. No difference in the EPCR gene H3 SNP G genotype frequency was found between RA and HC. This SNP was significantly correlated with higher sEPCR levels in HC but not in RA patients. In RA, plasma sEPCR levels were positively correlated with IL-6, IL-17, sCD14, anti-CCP and rheumatoid factor. In contrast, mEPCR levels on T cells and natural killer cells (NK) were inversely associated with disease activity measures including 28/66 swollen joint count, 28/68 tender joint count and/or DAS28-CRP/ESR scores, and positively correlated with EPCR gene H3 SNP, which was also correlated with lower disease activity measures in RA. Conclusion: Our findings suggest that EPCR may play an important role in RA, with plasma sEPCR being potentially associated with inflammatory markers and mEPCR and the EPCR gene H3 SNP possibly related to disease activity measures.