Circulating PD-1hi CXCR5– and CXCR5+ CD4 T cells are elevated in patients with newly diagnosed giant cell arteritis, and predict relapse

• Published in: Rheumatology (Oxford, England) Vol. 64; no. 6; pp. 3996 - 4004
• Main Authors: Monjo-Henry, Irene, Nieto-Carvalhal, Beatriz, Uyaguari, Mariela, García-Carazo, Sara, Balsa, Alejandro, de Miguel, Eugenio, Miranda-Carús, María-Eugenia
• Format: Journal Article
• Language: English
• Published: England Oxford Publishing Limited (England) 01.06.2025
• Subjects: Aged; Aged, 80 and over; Apoptosis; Arteritis; Autoimmunity; B7-H1 Antigen; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; Cell death; CXCR5 protein; Female; Giant Cell Arteritis - blood; Giant Cell Arteritis - diagnosis; Giant Cell Arteritis - immunology; Humans; Leukocytes (mononuclear); Lymphocytes; Lymphocytes T; Male; Middle Aged; PD-1 protein; PD-L1 protein; Peripheral blood mononuclear cells; Programmed Cell Death 1 Receptor - immunology; Prospective Studies; Receptors, CXCR5 - blood; Receptors, CXCR5 - immunology; Recurrence; Vasculitis; Tph cells; giant cell arteritis; Tfh cells; PD-1; biomarkers
• ISSN: 1462-0324; 1462-0332; 1462-0332
• DOI: 10.1093/rheumatology/keaf001

GCA is a large/medium-vessel granulomatous vasculitis, and the Programmed Cell Death 1/Programmed Cell Death-ligand-1 (PD-1/PD-L1) coinhibitory pathway seems to be implicated in its pathogenesis. CD4 T cells expressing high PD-1 levels, CD4+CXCR5-PD-1hi peripheral helper (Tph) and CD4+CXCR5+PD-1hi follicular helper T cells (Tfh) are key mediators of autoimmunity. Their frequencies are elevated in the peripheral blood of subjects with several autoimmune conditions but have not been investigated in GCA. Our objective was to study the frequency of circulating Tph (cTph) and Tfh (cTfh) in patients with newly diagnosed GCA (nGCA). Prospective, non-interventional study on consecutive patients referred to our US GCA fast-track clinic over a period of 24 months. Peripheral blood was drawn immediately upon initial diagnosis. For each patient, an age- and gender-matched healthy control (HC) was included. Peripheral blood mononuclear cells isolated by Ficoll-Hypaque were examined by cytometry. Patients were subsequently treated with standard therapy according to the updated 2018 EULAR recommendations. Sixty-five nGCA patients were included. As compared with HC, nGCA patients presented at baseline with an increased frequency of cTph and cTfh cells. Among the 46 patients who could be followed up for 12 months, 19 experienced a relapse. The baseline frequency of cTph and cTfh cells had been significantly lower in patients who relapsed as compared with those who did not. A cTph cell frequency <1.0 predicted relapse with a sensitivity of 90% and specificity of 93%. nGCA patients demonstrate increased baseline cTph and cTfh cell frequencies. Lower baseline proportions of cTph and cTfh cells associate with relapse.