92. Aberrant Phenotype Of Circulating Antigen Presenting Cells in Giant Cell Arteritis and Polymyalgia Rheumatica Patients

Background: Giant Cell Arteritis (GCA) and Polymyalgia Rheumatica (PMR) are overlapping diseases occurring exclusively in people older than 50 years. Antigen-presenting cells (APCs), including monocytes and dendritic cells (DCs), are main contributors to the immunopathology of GCA and PIn GCA tissues, DCs may be prone to activation, leading to chemokine production and recruitment of CD4+ T-cells and monocytes to the arterial wall. However, little is known about APC phenotypes in the peripheral blood at the time of GCA/Pdiagnosis. Therefore, we aimed to investigate the phenotype of the circulating APCs in GCA and Ppatients.

Methods: APCs among peripheral blood mononuclear cells (PBMCs) of treatment-naive GCA and Ppatients were compared to those in age- and sex-matched healthy controls (HCs) using flow cytometry (n=15 in each group). Using a 14-colour panel, we identified three monocyte subsets: classical (CD14+CD16-), intermediate (CD14+CD16+), and non-classical (CD14lowCD16+) monocytes. DC subsets were defined as CD14/CD16/CD19 negative cells with high Human Leukocyte Antigen – (HLA-DR) expression, and were subdivided in CD303+CD11c- plasmacytoid DCs (pDCs), CD11c+CD141+ conventional DCs (cDC1) and CD11c+CD1c+ conventional DCs (cDC2). Each of these subsets was analysed for expression of Toll-like receptor 4 (TLR4), TLR2, CD86, CCR7, Programmed death- ligand 1 (PD-L1), CD40, HLA-and CD11c by assessing the mean-fluorescence intensity of these markers.

Results: Compared to HCs, non-classical monocytes of GCA and of Ppatients had a significantly lower expression of TLR2, HLA-and CD11c, whereas CD86 expression was significantly lower on non-classical monocytes of Ppatients only. In contrast, CCR7 expression by non-classical monocytes of GCA and Ppatients was significantly higher (Figure 1). Expression of CD40 appeared to be lower in Ppatients’ intermediate monocytes. Even though no phenotypical and numerical differences were observed for DCs in the peripheral blood, cDC2 counts correlated negatively with CRP levels (r=-0.64 for GCA, r=-0.43 for PMR).

Conclusions: Circulating non-classical monocytes, but not DCs, display an altered phenotype in GCA and Ppatients at diagnosis. These cells, thought to be pro-inflammatory and representing the end stage of monocyte maturation in the blood, display features of decreased activation. The results suggest an exhausted  or an early senescent phenotype of non-classical monocytes possibly caused by the inflammatory process. Moreover, their increased CCR7 expression could indicate an increased capacity to migrate to tissues expressing high CCR7 ligands, a notion to be further investigated.

Disclosures: AB was a consultant for Grünenthal Gmbh until 2017. EB and KSMvdG as employees of the UMCG received speaker/consulting fees from Roche paid to the UMCG.

Figure 1. Mean fluorescence intensity of CCR7 and HLA-on non-classical monocytes in GCA and Ppatients compared to HCs (n=15 per group).