Abstract
ObjectiveSuitable biomarkers are essential for the design of therapeutic strategies in personalized medicine. Vasoactive intestinal peptide (VIP) has demonstrated immunomodulatory properties in autoimmune murine and ex vivo human models. Our aim was to study serum levels of VIP during the follow-up of an early arthritis (EA) cohort and to analyze its value as a biomarker predicting severity and therapeutic requirements.MethodsData from 91 patients on an EA register were analyzed (76% rheumatoid arthritis (RA), 24% undifferentiated arthritis, 73% women, and median age 54 years; median disease duration at entry, 5.4 months). We collected per protocol sociodemographic, clinical, and therapeutic data. VIP levels were determined by enzyme immunoassay in sera harvested from the 91 patients (353 visits; 3.9 visit/patient) and from 100 healthy controls. VIP values below the 25th percentile of those assessed in healthy population were considered low. To determine the effect of independent variables on VIP levels, we performed a longitudinal multivariate analysis nested by patient and visit. A multivariate ordered logistic regression was modeled to determine the effect of low VIP serum levels on disease activity at the end of follow-up.ResultsVIP concentrations varied considerably across EA patients. Those fulfilling the criteria for RA had the lowest values in the whole sample, although no significant differences were observed compared with healthy donors. Disease activity, which was assessed using DAS28, inversely correlated with VIP levels. After a two-year follow-up, those patients with low baseline levels of VIP displayed higher disease activity and received more intensive treatment.ConclusionPatients who are unable to up-regulate VIP seem to have a worse clinical course despite receiving more intense treatment. Therefore, measurement of VIP levels may be suitable as a prognostic biomarker.
Highlights
Rheumatoid arthritis (RA) is a systemic autoimmune disease with a heterogeneous clinical spectrum
The main difference between these two subgroups was a higher frequency of female patients in the RA group, in which more severe disease at baseline and a higher prevalence of rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPA) positivity were found (Table 1)
No significant differences were detected between the groups in variables expressing a subjective component such as pain, global disease assessment by patient, tender joint count, and Health Assessment Questionnaire score (HAQ)
Summary
Rheumatoid arthritis (RA) is a systemic autoimmune disease with a heterogeneous clinical spectrum. Recent efforts to improve outcome in patients with RA have focused on the early stages of the disease [1], when aggressive treatment can slow progression and change long-term course Another crucial therapeutic goal is to delay/prevent progression of undifferentiated arthritis (UA) and one of the challenges faced by rheumatologists is the classification of these patients. Many studies have attempted to identify prognostic markers in early RA or UA that correlate with disease progression in order to establish which patients are at risk for poor outcome or, which are destined to have a more benign disease so that overtreatment can be avoided [2]. Identification of such predictive tools would help us tailor treatment
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