Abstract
BackgroundThe vasoactive intestinal peptide (VIP) receptors VPAC1 and VPAC2 mediate anti-inflammatory and immunoregulatory responses in rheumatoid arthritis (RA). Data on the expression of these receptors could complement clinical assessment in the management of RA. Our goal was to investigate the correlation between expression of both receptors and the 28-Joint Disease Activity Score (DAS28) in peripheral blood mononuclear cells (PBMCs) from patients with early arthritis (EA). We also measured expression of IL-6 to evaluate the association between VIP receptors and systemic inflammation.MethodsWe analyzed 250 blood samples collected at any of the 5 scheduled follow-up visits from 125 patients enrolled in the Princesa Early Arthritis Register Longitudinal study. Samples from 22 healthy donors were also analyzed. Sociodemographic, clinical, and therapeutic data were systematically recorded. mRNA expression levels were determined using real-time PCR. Then, longitudinal multivariate analyses were performed.ResultsPBMCs from EA patients showed significantly higher expression of VPAC2 receptors at baseline compared to healthy donors (p<0.001). With time, however, VPAC2 expression tended to be significantly lower while VPAC1 receptor expression increased in correlation with a reduction in DAS28 index. Our results reveal that more severe inflammation, based on high levels of IL-6, is associated with lower expression of VPAC1 (p<0.001) and conversely with increased expression of VPAC2 (p<0.001). A major finding of this study is that expression of VPAC1 is lower in patients with increased disease activity (p = 0.001), thus making it possible to differentiate between patients with various degrees of clinical disease activity.ConclusionPatients with more severe inflammation and higher disease activity show lower levels of VPAC1 expression, which is associated with patient-reported impairment. Therefore, VPAC1 is a biological marker in EA.
Highlights
Rheumatoid arthritis (RA) is a common autoimmune disease with a heterogeneous clinical course and various pathogenic mechanisms leading to chronic synovitis and joint destruction
peripheral blood mononuclear cells (PBMCs) from early arthritis (EA) patients showed significantly higher expression of VPAC2 receptors at baseline compared to healthy donors (p
VPAC2 expression tended to be significantly lower while VPAC1 receptor expression increased in correlation with a reduction in DAS28 index
Summary
Rheumatoid arthritis (RA) is a common autoimmune disease with a heterogeneous clinical course and various pathogenic mechanisms leading to chronic synovitis and joint destruction. Frequent measurement of disease activity is recommended by the American College of Rheumatology/ European League Against Rheumatism [3], the European League Against Rheumatism [4] and the treat-to-target international task force [5], with a clear goal, namely, reducing, if not eliminating, inflammation to facilitate remission in the fastest possible way [6]. For this reason, many investigators aim to identify biological markers reflecting underlying pathophysiological processes associated with the clinical activity of RA. We measured expression of IL-6 to evaluate the association between VIP receptors and systemic inflammation
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