Clinical Relevance of VPAC1 Receptor Expression in Early Arthritis: Association with IL-6 and Disease Activity

Abstract

Background: The 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 theassociation between VIP receptors and systemic inflammation. Methods: We 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 realtime PCR. Then, longitudinal multivariate analyses were performed. Results: PBMCs 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 thatexpression 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.