Increased endothelial protein C receptor correlates with disease activity and inflammatory cytokines in rheumatoid and psoriatic arthritis patients

Aim: Endothelial protein C receptor (EPCR) is an anticoagulant receptor that is highly expressed in the synovial tissues and plasma from patients with rheumatoid arthritis (RA). However, it is not known if EPCR levels correlate with disease activity and other inflammatory markers in RA and psoriatic arthritis (PsA).

Methods: 37 RA (54.5 ± 17.3 years old) and 17 PsA (54.3 ± 15.7 years old) patients were recruited via the Australian Arthritis and Autoimmune Biobank Collaborative (A3BC). Gender, age and disease activity scores were collected from these patients. EPCR, IL-6, IL-17 and soluble (s)CD14 in plasma were measured by enzyme-linked immunosorbent assay. EPCR on circulating CD4 T cell was detected by flow cytometry. Correlations were analysed by GraphPad Prism 9.

Results: In RA, plasma EPCR was 303.3 ± 684 ng/mL, and positively correlated with 66 Swollen Joint Count (r = 0.42, P = 0.015), 28 Swollen Joint Count (r = 0.45, P = 0.009) and DAS28-CRP score (r = 0.535, P = 0.015). A positive correlation was also found between plasma EPCR and IL-6 (r = 0.927, P < 0.0001), IL-17 (r = 0.975, P < 0.0001) and sCD14 (r = 0.395, P = 0.017). EPCR on circulating T cells showed a positive correlation with 66 Swollen Joint Count (r = 0.449, P = 0.011), 68 Tender Joint Count (r = 0.464, P = 0.008), 28 Tender Joint Count (r = 0.443, p = 0.013) and 28 Swollen Joint Count (r = 0.396, P = 0.027). However, EPCR on CD4 T cells did not correlate with DAS28-CRP score or DAS28-ESR score. In PsA, plasma EPCR was 440 ± 996 ng/mL, and correlated with plasma IL-6 (r = 0.905, P < 0.000001), IL-17 (r = 0.805, P < 0.00001) and sCD14 (r = 0.531, P = 0.028), but did not show any correlation with disease scores. Instead, EPCR on circulating CD4 T cells positively correlated with DAS28-CRP score (r = 0.957, p = 0.011) and DAS28-ESR score (r = 0.903, P = 0.036). No correlation was found between EPCR on CD4 T cells and plasma EPCR.

Conclusions: EPCR levels positively associated with disease activity and cytokines IL-6 and IL-17, maybe a potential therapeutical target for RA and PsA.