ANGIOGENIC T-CELL DEPLETION OCCURS DURING THE EARLIEST PHASES OF RHEUMATOID ARTHRITIS LINKED TO SUBCLINICAL VASCULAR STIFFNESS

Background vascular insult accounts for the cardiovascular (CV) risk excess in rheumatoid arthritis (RA). Angiogenic T cells (Tang), which are responsible of vascular repair, have been described to be reduced in established RA with overt CV disease. However, whether Tang are altered during the earliest stage of the disease and related to subclinical CV findings is unknown. Objectives to evaluate circulating Tang levels in the very early stage of RA, including clinically suspect arthralgia (CSA), and their associations with subclinical CV endpoints (subclinical atherosclerosis and vascular stiffness). Methods 84 RA patients (2010 EULAR/ACR classification criteria), 14 CSA individuals (EULAR criteria) and 28 matched healthy controls (HC) were recruited. All patients were untreated at the time of sampling. Tang (CD3+CD31+CXCR4+) frequency was assessed by flow cytometry in peripheral blood samples. Plaque occurrence, cIMT and stiffness parameters were analyzed by Doppler ultrasound in internal carotid, middle cerebral and basilar arteries. Lipoprotein analyses were performed by NMR. Results Tang were decreased in RA and CSA groups compared to HC (both p<0.010). Whereas Tang frequency was negatively correlated with very low density lipoproteins features (cholesterol and triglyceride content, size distribution and particle number) in HC and positively with HDL (cholesterol content and particle number), these associations were lacking in RA and CSA groups. Tang levels were not related to individual traditional CV risk factors, body mass index, wait circumference (all p>0.050) nor with the modified SCORE (r=-0.070, p=0.542) or Framingham Risk Score (r=-0.013, p=0.907). On the contrary, disease activity accounted for the Tang depletion observed in RA (b[95% CI]; DAS28: -0.436 [-0.306, -0.109], p=<0.001; SDAI: -0.020 [-0.032, -0.008], p=0.002). Tang levels were unrelated to the duration of the symptoms both in RA and CSA. In RA patients, Tang frequency was not associated with atherosclerosis plaque occurrence (p=0.556) or cIMT (r=0.136, p=0.245). However, Tang paralleled stiffness parameters: vascular strain (VS, r=0.373, p=0.013), vascular distensibility (VD, r=0.479, p=0.004), vascular stiffness (VSf, r=-0.400, p=0.007) and pressure-strain elastic modulus (PSEM, r=-0.373, p=0.013). Finally, Tang frequency was an independent predictor of stiffness parameters after adjusting for mSCORE, body mass index, DAS28, RF and ACPA positivity: VS (β=0.415, p=0.035), VD (β =0.361, p=0.028), VSf (β =-0.322, p=0.033) and PSEM (β =-0.346, p=0.016). Conclusion Tang depletion is an early event along RA development, associated with disease-related parameters and unrelated to traditional risk factors. Tang may be the missing, functional link between disease activity and CV outcomes. Altered Tang levels may be an early biomarker of premature vascular stiffness during the first stages of the disease. REFERENCES Disclosure of Interests None declared