SAT0027 CIRCULATING CD3+CD31+CXCR4+ T CELLS IN RHEUMATOID ARTHRITIS PATIENTS: CORRELATION WITH RETINAL MICROVASCULAR DAMAGE AND POTENTIAL EFFECT OF ABATACEPT THERAPY
Authors: Silvia Piantoni, Francesca Regola, Stefano Caletti, Rajesh Kumar, Cecilia Nalli, Chiara Bazzani, Claudia Rossini, Carolina De Ciuceis, Damiano Rizzoni, Angela Tincani, Paolo Airò
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> T-cells play a role in pathogenesis of rheumatoid arthritis (RA) and in its cardiovascular (CV) comorbidities [1]. CD3+CD31+CXCR4+T-cells may be involved in damaged endothelium repair [2]. The percentage of these cells in the peripheral blood was reported to be lower in RA than in healthy controls, as an effect of disease activity rather than of traditional CV risk factors [3]. Abatacept (ABA), a T-cell co-stimulation blocker, is approved for the treatment of RA. In addition to its effect on disease activity, it may have a CV protective action [4]. <h3>Objectives:</h3> To evaluate CD3+CD31+CXCR4+T-cells in a cohort of RA patients in correlation with disease activity, CV parameters, and the potential effect of ABA therapy. <h3>Methods:</h3> Thirty-one RA patients (median[10<sup>th</sup>-90<sup>th</sup>percentile] age=60[40-70] years, baseline C-reactive protein (CRP)-DAS28=4[3-5.4], body mass index (BMI)=21[17.3-28.6] kg/m<sup>2</sup>, rheumatoid factor (RF) positive:55%, anti-citrullinated peptide autoantibodies (ACPA) positive:77%) were enrolled. Thirteen patients were evaluated before and after 6 months of ABA therapy. Among them, in 5 patients without known CV risk factors (history of arterial hypertension, diabetes, hypercholesterolemia, previous CV events and smoking), a morphological evaluation of retinal arterioles was performed by adaptive optics, a validated technique quantifying microvascular damage [5]. The response to treatment was evaluated with the EULAR response criteria. Phenotypic analysis of peripheral blood T lymphocytes was made by flow-cytometry. <h3>Results:</h3> At baseline, no correlation was found between relative CD3+CD31+CXCR4+T-cell number and age, BMI, CRP DAS28, RF and ACPA titer. However, a negative correlation was observed with retinal wall thickness (Figure1). After ABA therapy (n=13), no significant differences were found between good-moderate responders (n=10) and non-responders (n=3), but the two groups seemed to show an opposite trend (T0 vs T6; from 23.8[4-45.4] to 11.9[5-38.7] and from 20.4[15.4-32.3] to 27.4[17.8-41]% of CD3+ cells, respectively). All 5 patients without known CV risk, evaluated also with adaptive optics, had a good EULAR response. A trend for reduction of CD3+CD31+CXCR4+T-cells after ABA therapy was also observed (19[7.9-45.6] vs 12.4[4.6-26.1]% of CD3+), as well as of the retinal wall thickness (14.4[12.9-16.2] vs 14.2[11.7-14.9] μm). A significant reduction of retinal wall cross-sectional area was observed (5123.3[4027.8-6145.5] vs 4852.3[3554.9-5788.2] μm<sup>2</sup>;p=0.04). <h3>Conclusion:</h3> In a subgroup of patients without known CV risk factors, CD3+CD31+CXCR4+T-cell number was inversely related to the possible presence of subclinical CV involvement, as evaluated by retinal microvascular damage. This improved after ABA therapy. These findings may suggest a possible value of CD3+CD31+CXCR4+T-cell number in the evaluation of microvascular damage, and a possible beneficial effect of ABA on the microcirculation in RA patients. <h3>Reference</h3> [1] Dessein PH, J Rheumatol2005. [2] Hur J, Circulation 2007. [3] Rodriguez Carrio J, ARD 2015. [4] Kallikourdis M, Nat Commun 2017. [5] De Ciuceis, J Hypertens2018. <h3>Acknowledgement:</h3> Bristol-Myers-Squibb Italy provided an unrestricted research grant for the study conduct. <h3>Disclosure of Interests:</h3> Silvia Piantoni: None declared, Francesca Regola: None declared, Stefano Caletti: None declared, Rajesh Kumar: None declared, Cecilia Nalli: None declared, Chiara Bazzani: None declared, Claudia Rossini: None declared, Carolina De Ciuceis: None declared, Damiano Rizzoni: None declared, Angela Tincani Consultant for: UCB, Pfizer, Abbvie, BMS, Sanofi, Roche, GSK, AlphaSigma, Lillly, Jannsen, Cellgene, Novartis, Paolo Airò: None declared