POS0494 ARTERIAL WALL DENDRITIC CELLS IN GIANT CELL ARTERITIS (GCA) AND POLYMYALGIA RHEUMATICA (PMR)

Abstract

BackgroundPolymyalgia rheumatica (PMR) is an inflammatory rheumatic disease (1) associated in 16 to 21% of cases with giant cell arteritis (GCA). The association of these two conditions raises the question of a pathophysiological continuum between PMR and GCA. An early study reported mature arterial wall dendritic cells (DC) in patients with GCA or PMR leading, during GCA, to CD4+ T cell recruitment and the development of vasculitis (2). However, these data have never been confirmed in other studies. There are 3 main types of DC: plasmacytoid DC (expressing CD123), conventional DC (cDC) expressing CD141 (cDC1) or CD1c (cDC2) and monocyte-derived DC (mo-DC) expressing CD14.ObjectivesThe aim of this study was to describe the arterial wall infiltrating DCs, their phenotype and maturation state, during PMR and GCA.MethodsUsing temporal artery biopsies (TAB) from patients with PMR, GCA and healthy controls, the level of expression of CD11c, CD83, CCR7, CCR6, CD1c, CCL18, CCL19, CCL20, CCL21, GM-CSF, CD3, CD68 genes was assessed by RT-PCR. Expression of markers of DC lineage (CD209), DC maturation state (CD83 and CCR7) and DC origin (CD14, CD68, CD1c, CD141) were studied by confocal microscopy.ResultsFourty-one patients were included (14 GCA, 16 PMR, 11 controls). Within the arterial wall, DCs were identified in GCA patients, with a mature DC phenotype (CD209+CD83+CCR7+). DC were present in all three layers of the arterial wall and also expressed CD14 and often CD68 but neither CD1c nor CD141, which could be explained by a monocytic/macrophage origin. TAB from GCA patients were characterized by a high level of expression of CD83, CCR7, CCR6, CCL18, CCL19, CCL20, CD11c, GM-CSF, CD3 and CD68 gene. This expression was significantly higher (p<0.05) compared to the control and PMR groups.Confocal microscopy analyses of arteries from the PMR and controls did not detect the presence of DCs into the arterial wall. In addition, level of expression of CD83, CCR7, CCL18, CCL19, CCL21 and CD68 genes in temporal arteries was comparable between PMR and healthy controls.ConclusionThis work confirms the presence of mature CD209+CD83+CCR7+ DCs within the arterial wall in GCA. The phenotype of these DCs mainly fits with DC of monocytic origin (mo-DCs). However, both by RT-PCR and confocal microscopy, we did not identify DCs in the arterial wall of PMR patients. This discrepancy with previous work (3) could be explained by a better diagnosis of GCA in PMR patients since the development of imaging techniques.