Extensive study of CCN4, VCAM-1, MMP-3, and GM-CSF as reliable markers for disease activity in rheumatoid arthritis

Abstract

Background

The involvement of Wnt-1-induced secreted protein-1 (WISP1/CCN4) in several inflammatory reaction has recently been proposed. Nevertheless, this protein's involvement in rheumatoid arthritis (RA) remains debated. Associations between poorly diagnosed RA and several classical markers derived from demography and biochemistry have been reported.

Aim

We sought to investigate the reliability and effectiveness of serum concentrations of CCN4, vascular cell adhesion molecule-1 (VCAM-1), matrix melloprotenase-3 (MMP-3), and granulocyte-macrophage colony-stimulating factor (GM-CSF) in monitoring and predicting RA and bone damage, and their correlation with RA disease course.

Methods

The study analyzed 128 patients with RA, comprising 68 newly diagnosed and 60 previously diagnosed patients, as well as 60 controls. Biomarker levels were measured with enzyme linked immuno-sorbent assays. Routine laboratory parameters such as serological, clinical, biochemical, and hematological parameters were additionally measured. Demography, anthropometry, and clinical symptom data were collected through interviews and a questionnaire. The joint disease activity score 28 (DAS28) was used to determine disease activity.

Results

Concentrations of four biomarkers were significantly higher in the RA group than the healthy controls. Elevated biomarker concentrations were also observed in patients with high, rather than moderate or low, DAS28-ESR activity status, except for monocyte count, hematocrit (%), and urea level. Furthermore, CCN4 level positively correlated with VCAM-1, MMP-3, and GM-CSF levels, DA-S28-CRP and DAS28-ESR. The levels of three predictive markers, CCN4, VCAM-1, and MMP-3, were elevated in non-treated patients, whereas GM-CSF level showed no difference. The highest area under the curve was 73.3% for CCN4, with 93.3% sensitivity and 64.7% specificity.

Conclusion

Our data suggest that CCN4 can be reliably used to indicate activity and therapeutic response associated with RA, thus facilitating earlier RA diagnosis.