Journal Article

POS0247 CIRCULATING CD4+CXCR5-PD-1hiICOS+ CELLS ARE ELEVATED INPATIENTS WITH NEWLY DIAGNOSED GIANT CELL ARTERITIS AND ASSOCIATE WITH THE CLINICAL OUTCOME

Miranda-Carus, M. E., Casado-Juárez, I., Monjo-Henry, I., Uyaguari Morocho, M. D. C., Nieto-Carvalhal, B., De Miguel, E., Balsa, A.

2024

Overview

Background:Giant cell arteritis (GCA) is a large-vessel granulomatous vasculitis [1,2]. It is characterized by the presence at the inflamed arterial walls, of activated PD-1+ CD4 T cells [1,2]; this contrasts with observations indicating that a defect of PD-1 signaling is implicated in the pathogenesis of GCA [2]. A population of CD4+CXCR5-PD-1 cells, termed Tph cells, has been described at the inflamed synovium and peripheral blood of patients with Rheumatoid Arthritis [3], and seem to play a pathogenic role in this condition [3].Objectives:To study the frequencies of circulating total Tph (cTph) and activated ICOS+Tph (cICOS+Tph) cells in the peripheral blood of patients with newly diagnosed GCA (nGCA) and examine whether they are related with the clinical outcome.Methods:This is a prospective non-interventional study performed on consecutive patients referred to our ultrasound (US) GCA fast track clinic, in whom newly diagnosed GCA (nGCA) was clinically confirmed (2022 ACR/EULAR criteria) over a period of 18 months. Peripheral blood was drawn immediately upon confirmation and after obtaining written informed consent. For each patient, an age and gender-matched healthy control (HC) was also studied. PBMCs isolated by Ficoll- Hypaque gradient were stained with antibodies to CD3, CD4, CD45RA, CD45RO, CXCR5, ICOS, PD-1, and examined by flow cytometry. Patients were treated with standard therapy according to clinical response.Results:A total of 60 nGCA patients were included (mean age 82 years, 58 % female). As compared with HC, nGCA patients presented at baseline with an increased frequency of cTph and ICOS+cTph cells. Among the 37 patients who could be followed up for 12 months (the remaining 23 have been diagnosed less than 12 months ago), 15 (40.5%) experienced a relapse (2018 EULAR recommendations; symptoms plus: elevation of acute phase reactants and/or positive US). Interestingly, the baseline frequency of cTph and ICOS+cTph cells had been significantly lower in patients who relapsed as compared with those who did not.Conclusion:Newly diagnosed GCA patients demonstrate an increased frequency of cTph and ICOS+cTph cells. Lower basal proportions of cTph and cICOS+cTph cells are associated with relapse.REFERENCES:[1] Weyand CM, Berry GJ & Goronzy JJ. J Leukoc Biol. 2018.[2] Zhang H, et al. Proc Natl Acad Sci U S A. 2017.[3] Rao DA, et al. Nature. 2017.Acknowledgements:NIL.Disclosure of Interests:Maria-Eugenia Miranda-Carus Gebro Pharma, BMS, Beatriz Nieto-Carvalhal: None declared, Irene Monjo-Henry: None declared, Mariela del Carmen Uyaguari Morocho: None declared, Irene Casado-Juárez: None declared, Alejandro Balsa BMS, Eugenio De Miguel: None declared.

• Publisher: BMJ Publishing Group Ltd and European League Against Rheumatism,Elsevier B.V,Elsevier Limited
• Subject: Adaptive immunity / Arteritis / Biomarkers / CD3 antigen / CD4 antigen / CD45RA antigen / CXCR5 protein / Flow cytometry / Inflammation / Lymphocytes T / Non-pharmacological intervention / PD-1 protein / Peripheral blood / Rheumatoid arthritis / Rheumatoid synovitis / Scientific Abstracts / Vasculitis / Vein & artery diseases