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

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2016 Feb 17

PMID 26881970

Citations 10

Authors

Iria V Seoane

Ana M Ortiz

Lorena Piris

Amalia Lamana

Yasmina Juarranz

Rosario Garcia-Vicuna

Isidoro Gonzalez-Alvaro

Rosa P Gomariz

Carmen Martinez

Affiliations

Soon will be listed here.

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 the association 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 real-time 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 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.

Conclusion: Patients 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.

Citing Articles

VIP/VPAC Axis Expression in Immune-Mediated Inflammatory Disorders: Associated miRNA Signatures.

Lamana A, Castro-Vazquez D, de la Fuente H, Triguero-Martinez A, Martinez-Hernandez R, Revenga M Int J Mol Sci. 2022; 23(15).

PMID: 35955723 PMC: 9369218. DOI: 10.3390/ijms23158578.

Comparative Study of Senescent Th Biomarkers in Healthy Donors and Early Arthritis Patients. Analysis of VPAC Receptors and Their Influence.

Villanueva-Romero R, Lamana A, Flores-Santamaria M, Carrion M, Perez-Garcia S, Triguero-Martinez A Cells. 2020; 9(12).

PMID: 33291545 PMC: 7761848. DOI: 10.3390/cells9122592.

Vasoactive intestinal peptide axis is dysfunctional in patients with Graves' disease.

Carrion M, Ramos-Levi A, Seoane I, Martinez-Hernandez R, Serrano-Somavilla A, Castro D Sci Rep. 2020; 10(1):13018.

PMID: 32747757 PMC: 7400547. DOI: 10.1038/s41598-020-70138-3.

A Clinical Approach for the Use of VIP Axis in Inflammatory and Autoimmune Diseases.

Martinez C, Juarranz Y, Gutierrez-Canas I, Carrion M, Perez-Garcia S, Villanueva-Romero R Int J Mol Sci. 2019; 21(1).

PMID: 31861827 PMC: 6982157. DOI: 10.3390/ijms21010065.

An Overview of VPAC Receptors in Rheumatoid Arthritis: Biological Role and Clinical Significance.

Gomariz R, Juarranz Y, Carrion M, Perez-Garcia S, Villanueva-Romero R, Gonzalez-Alvaro I Front Endocrinol (Lausanne). 2019; 10:729.

PMID: 31695683 PMC: 6817626. DOI: 10.3389/fendo.2019.00729.

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