title: 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 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Departamento de Biología Celular, Facultad de Biología, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Iria V
authors.initials: IV
authors.lastname: Seoane
authors.affiliation: Servicio de Reumatología, Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria la Princesa, Madrid, Spain.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Ortiz
authors.affiliation: Unidad de Apoyo Metodológico, Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria la Princesa, Madrid, Spain.
authors.forename: Lorena
authors.initials: L
authors.lastname: Piris
authors.affiliation: Servicio de Reumatología, Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria la Princesa, Madrid, Spain.
authors.forename: Amalia
authors.initials: A
authors.lastname: Lamana
authors.affiliation: Departamento de Biología Celular, Facultad de Biología, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Yasmina
authors.initials: Y
authors.lastname: Juarranz
authors.affiliation: Servicio de Reumatología, Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria la Princesa, Madrid, Spain.
authors.forename: Rosario
authors.initials: R
authors.lastname: García-Vicuña
authors.affiliation: Servicio de Reumatología, Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria la Princesa, Madrid, Spain.
authors.forename: Isidoro
authors.initials: I
authors.lastname: González-Álvaro
authors.affiliation: Departamento de Biología Celular, Facultad de Biología, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Rosa P
authors.initials: RP
authors.lastname: Gomariz
authors.affiliation: Departamento de Biología Celular, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Martínez
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000503:physiopathology; D016022:Case-Control Studies; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D015850:Interleukin-6 / Q000097:blood* / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D051239:Receptors, Vasoactive Intestinal Peptide, Type II / Q000097:blood* / Q000378:metabolism*; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I / Q000097:blood* / Q000378:metabolism*; D012720:Severity of Illness Index; D015398:Signal Transduction; D012923:Social Class; D013997:Time Factors; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; D014660:Vasoactive Intestinal Peptide