Expression of Neopterin and Chemokines in Rheumatoid Arthritis and Cardiovascular Disease

Abstract

In chronic inflammatory processes like rheumatoid arthritis (RA) and cardiovascular diseases (CVD) the role of pteridines and chemokines in the immune response is of great interest. The objectives of the study were to obtain information about an involvement of specific chemokines on the inflammatory process in patients with RA and CVD with activated production of the pteridine neopterin. 113 patients with RA according to American College of Rheumatology criteria including 24.8% suffering from CVD were included in the study (23% male, 77% female). For the assessment of monocyte activation and chemotaxis as well as the proinflammatory influence of chemokines on B-cells and angiogenesis in RA, neopterin and the chemokines CCL2, CXCL13 and CX3CL1 were measured by radio-and enzyme-immunoassays in serum. Neopterin and chemokines were all found in high concentrations. Neopterin significantly correlated with all chemokines: CXCL13 (r s = 0.368; p <0.0001), CX3CL1 (r s = 0.241; p <0.02), CCL2 (r s = 231; p <0.02), demonstrating high neopterin levels in RA patients to have a strong association to the chemokine induced chemotaxis of B-cells (CXCL13) and mononuclear cells (CX3CL1, CCL2). Significantly elevated concentrations of neopterin and CXCL13 were seen in patients with RA plus CVD compared to RA without CVD (p <0.03). The high incidence of cardiovascular diseases in rheumatoid arthritis seems to be associated with enhanced mononuclear (neopterin, CCL2) and B-cell activation (CXCL13), and as a consequence increased immune system activity.

Clinical usefulness of serum neopterin in children with juvenile idiopathic arthritis

“…However, many authors claimed on the usefulness of this parameter in patients with rheumatoid arthritis (RA) [16,[19][20][21][22]. Importantly, our findings are consistent with the above-mentioned data; this probably 14.196 reflects similarities in the pathogenesis of JIA and RA, and the involvement of Th1 response in these two conditions.…”

“…The concentrations of all these markers were high, especially in individuals with cardiovascular comorbidities. Furthermore, the authors documented a significant correlation between the concentration of NPT and the levels of studied chemokines [16].…”

“…However, contrary to the autoantibody titers, NPT was a useful marker irrespective of patient age [22]. Fagerer et al [16] studied the serum concentrations of NPT and various chemokines (CCL2, CXCL13, CX3CL1) in 113 patients with RA. The concentrations of all these markers were high, especially in individuals with cardiovascular comorbidities.…”

“…Activated lymphocytes T were proved to synthesize interferon-γ, which stimulates the release of NPT from monocytes/macrophages [5][6][7]. Previous studies confirmed the usefulness of NPT as a clinical marker of many autoimmune conditions [5,8,9], e.g., in gastroenterology [10][11][12][13], endocrinology [14], and rheumatology [15,16].…”

Association of neopterin as a marker of immune system activation and juvenile rheumatoid arthritis activity

“…The difference in the results may be attributed to the adult age group of their study compared to the young age group in the present study. Also Fagerer et al, in 2013, 21 studied the involvement of specific chemokines in the inflammatory process of patients with RA and cardiovascular disease with activated production of the pteridine neopterin. In agreement with the current study, they found high neopterin levels in RA patients and significantly elevated concentrations of neopterin in patients with RA plus cardiovascular disease (CVD) compared to RA without CVD (p < 0.03).…”