Background Rheumatoid Arthritis (RA) is a heterogeneous disease, not only in the course but also in the response to treatment (1). So, a major challenge is the classification of patients according to the disease severity/mildness to apply customized therapeutic strategies. Low vasoactive intestinal peptide (VIP) serum levels are associated to a worse clinical course in Early Arthritis (EA) (2) and the expression of its receptor VPAC1 is associated with disease activity (3).
Objectives To identify in an Early Arthritis cohort associations between clinical parameters of severity and serum VIP levels or expression of their receptors VPAC1 and VPAC2.
Methods We studied 212 patients from the PEARL (Princesa Early Arthritis Registry Longitudinal) study. Follow-up includes five visits (0, 6, 12, 24 and 60 months) in which we collect demographic, clinical, laboratory, therapeutic and radiological data, as well as biological samples. Since there is not a global disease severity variable for RA, we stratified severity as follows: A) remission after two years of follow-up defined as SDAI <3.3 (4). B) Global Disease Assessment by Physician >75th percentile of the population (severe disease) or >25th percentile (mild disease). C) Median value in our population of the Δ erosion score (SvdH method assessed in hands) after two years of follow-up. VIP levels were determined by enzyme immunoassay and mRNA expression levels of VIP receptors in PBMCs by real-time PCR. To analyze the association between severity/mildness and the expression of VIP/VPAC we use several parametric and non-parametric hypothesis testing (t-test, ANOVA and Kruskal-Wallis) using Stata 12 for Windows (StataCorp PL, College Station, TX, USA).
Results We observed a trend towards higher baseline VIP serum levels in patients who reached remission in terms of SDAI (p=0.1169). Patients no achieving remission showed lower VPAC1 expression (p=0.0494). Severe patients defined by GDAPh displayed a clear trend to lower VIP levels (p=0.081). Those patients also exhibited significant lower VPAC1 expression levels (p=0.0276). Concerning bone erosion score, we did not observe a significant association with VIP levels; interestingly we found that those patients classified as “severe” by erosion score displayed lower VPAC1 expression levels (p=0.0722) and higher levels of VPAC2 (p=0.0253).
Conclusions VIP serum levels and VPAC1 and 2 receptors expression are associated with a more severe phenotype in EA patients stratified by SDAI, GDAPh and bone erosion.
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Acknowledgements This work has been supported by Instituto de Salud Carlos III, Spain, cofinanced by FEDER, European Union: RETICS program, Red de Investigaciόn en Inflamaciόn y Enfermedades Reumáticas (RD16/0012/0008 (RPG) and RD16/0012/0011 (IGA) and the projects PI12/00758 (RPG), PI14/00477 (CMM) and PI14/00442 (IGA).
Disclosure of Interest None declared