POS1440 EVIDENCE FOR INCREASED RESPONSIVENESS TO INTERFERON TYPE I IN CD8+ T CELLS IN PATIENTS WITH GIANT CELL ARTERITIS

• Published in: Annals of the rheumatic diseases Vol. 82; no. Suppl 1; p. 1074
• Main Authors: M Van Nieuwland, Esen, I, Reitsema, R, Abdulahad, W, Y Van Sleen, Sandovici, M, Brouwer, E, L Van Bon
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group LTD 01.06.2023
• Subjects: Arteries; Arteritis; Autoimmune diseases; Biomarkers; Biopsy; CD8 antigen; Effector cells; Flow cytometry; Gene expression; Immunohistochemistry; Interferon; Janus kinase; Kinases; Leukocytes (mononuclear); Lymphocytes; Lymphocytes T; Myxovirus resistance proteins; Pathogenesis; Patients; Peripheral blood; Polymyalgia rheumatica; Proteins; Stat1 protein; Transcription factors; Vasculitis; Vein & artery diseases; α-Interferon
• ISSN: 0003-4967; 1468-2060
• DOI: 10.1136/annrheumdis-2023-eular.2203

BackgroundGiant cell arteritis (GCA) is a vasculitis which can lead to severe complications when not timely recognized and treated. There is a need for the discovery of biomarkers to expedite the diagnostic process. Interferon type I (IFN-I) is increasingly recognized as a key player in a range of autoimmune diseases and might play a role in GCA pathogenesis [1]. However, evidence for IFN-I potentially linking innate and adaptive immune responses in GCA is limited. IFN-I activates the Janus kinase/signal transducers and activators of transcription (JAK-STAT) pathway, leading to an increased expression of interferon stimulated genes (ISGs).ObjectivesIn this study, IFN-I involvement in GCA pathogenesis is explored.MethodsPhopho-STAT1 (pSTAT1) expression was investigated in IFN-α-stimulated peripheral mononuclear cells (PBMCs) gated separately for CD8+ T-cells of patients with GCA (n=18), healthy controls (HC, n=15) and infection controls (n=11) by fluorescent cell barcoding and flow cytometry. Also, in 3 GCA patients and 3 HCs, single cell RNA sequencing was performed on PBMCs focusing on ISG expression. Furthermore, IFN-I induced myxovirus-resistance protein A (MxA) and CD8+ expression was investigated in temporal artery biopsies (TAB) of GCA patients (n=20) and GCA mimics (n=20) by immunohistochemistry.ResultspSTAT1 expression was increased in IFN-α stimulated CD8+ T-cells from patients with GCA compared to both HC (p<0.05) and infection controls. Furthermore, Interferon Induced Transmembrane Protein 1 (IFITM1) mRNA expression was upregulated in peripheral blood CD8+ T cells (p<0.001). MxA was present in TABs of 13/20 GCA patients compared to 2/20 mimics and MxA location co-localized with CD8+ expression in the tissue.ConclusionOur results provide evidence for IFN-I involvement in GCA pathogenesis, with CD8+ T cells as IFN-I responding effector cells. Increased pSTAT1, IFITM1 and MxA expression may reflect increased IFN-I responsiveness in CD8+ T-cells of GCA patients, both locally and systemically. These findings warrant further investigation regarding IFN-I induced biomarkers and IFN-I related novel therapeutic options.Reference[1]Nordborg C, Larsson K, Aman P, Nordborg E. Expression of the class I interferon-related MxA protein in temporal arteries in polymyalgia rheumatica and temporal arteritis. Scand J Rheumatol. 2009 Mar-Apr;38(2):144-8. doi: 10.1080/03009740802448841. PMID: 19177264.Figure 1MxA expression (brown staining) in temporal artery biopsy of A) a non-GCA patient and B) a biopsy-proven GCA patient.[Figure omitted. See PDF]Acknowledgements:NIL.Disclosure of InterestsNone Declared.