THU0440 Soluble ctla-4 is elevated in patients with polymyalgia rheumatica and correlates with vascular inflammation detected by pet/ct
Authors: D. Camellino, M. Marchiano, G. Pesce, G. Bianchi, M. Bagnasco, M.A. Cimmino, D. Saverino
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Positron emission tomography has shown the presence of large vessel vasculitis (LVV) in 30%–40% of patients with apparently isolated polymyalgia rheumatica (PMR)<sup>[1]</sup>, but biomarkers associated with the presence of LVV in PMR patients are still lacking. Anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) and its soluble (s) form, resulting from alternative splicing, are well-known immune checkpoint receptor<sup>[2]</sup> and have shown to play a role both in neoplastic<sup>[3]</sup> and autoimmune diseases<sup>[4]</sup>. The rationale for studying the involvement of CTLA-4 in PMR is provided by the evidence of drug-induced PMR/giant cell arteritis (GCA) in patients treated with ipilimumab, an anti-CTLA-4 antibody<sup>[5]</sup>. <h3>Objectives</h3> To evaluate the concentration of sCTLA-4 in PMR patients and to correlate it with vascular and joint inflammation. <h3>Methods</h3> Forty consecutive patients with of PMR, of whom 9 also had also GCA, underwent a standardised clinical examination and a PET/CT scan. Arterial and joint uptake of FDG were scored relative to liver and then summed up to obtain a total vascular score (TVS) and a total joint score (TJS). Patients were further subdivided into three groups for the analysis of the correlation with joint and vascular uptake: "vasculitic patients" (with grade-3 uptake in at least one vascular district), patients with intermediate uptake (excluded from this set of analyses), and patients without vasculitis. sCTLA-4, was evaluated by ELISA. Patients without autoimmune diseases served as controls. <h3>Results</h3> sCTLA-4 serum levels were significantly higher in PMR patients than in controls (p&lt;0.001, figure 1), although their concentrations did not significantly differ between patients with and without vasculitis. However, sCTLA-4 showed a positive correlation with TVS (r=0.35, p=0.025). figure 1. Panel A: comparison of serum level of sCTLA-4 in patients with PMR and controls (HD: healthy donors). Panel B: correlation between sCTLA-4 and total vascular score. <h3>Conclusions</h3> The present study provides the first evidence that serum sCTLA-4 concentration is elevated in PMR patients, and that it correlates with TVS. Although the exact mechanisms underlying the upregulation of sCTLA-4 remain elusive, we feel that aberrant production of cytokines, or abnormal activation of intercellular signalling pathways can be involved. <h3>References</h3> [1] Puppo C, Massollo M, Paparo F, Camellino D, et al. Giant Cell Arteritis: A Systematic Review of the Qualitative and Semiquantitative Methods to Assess Vasculitis with 18F-Fluorodeoxyglucose Positron Emission Tomography. Biomed Res Int2014;2014:574248. [2] Korhonen R, Moilanen E. Abatacept, a Novel CD80/86-CD28 T Cell Co-stimulation Modulator, in the treatment of rheumatoid arthritis. Basic Clin Pharmacol Toxicol2009;104(4):276–84. [3] Cranmer LD, Hersh E. The role of the CTLA4 blockade in the treatment of malignant melanoma. Cancer Invest2007;25(7):613–31. [4] Saverino D, Simone R, Bagnasco M, Pesce G. The soluble CTLA-4 receptor and its role in autoimmune diseases: an update. Autoimmun Highlights 2010;1(2):73–81. [5] Goldstein BL, Gedmintas L, Todd DJ. Drug-Associated Polymyalgia Rheumatica/Giant Cell Arteritis Occurring in Two Patients After Treatment With Ipilimumab, an Antagonist of CTLA-4. Arthritis Rheumatol2014;66(3):768–9. <h3>Disclosure of Interest</h3> None declared