Involvement of Monocyte Subsets in the Immunopathology of Giant Cell Arteritis

Monocytes/macrophages are critical in systemic and local inflammation in giant cell arteritis (GCA) and possibly in clinically overlapping polymyalgia rheumatica (PMR). Therefore, we aimed to understand the contribution of monocyte subsets and the CX3CR1-CX3CL1 and CCR2-CCL2 migratory pathways, to the pathology of GCA. Peripheral blood monocytes were enumerated in samples from newly-diagnosed, untreated GCA and PMR patients and after prednisone-induced remission. The distribution of classical (CD14^brightCD16^neg) and the more pro-inflammatory, intermediate (CD14^brightCD16+) and non-classical (CD14^dimCD16+) monocyte subsets was analysed by flow cytometry. The phenotype of macrophages in temporal artery biopsies (TABs) from GCA patients was studied by immunohistochemistry and immunofluorescence. A clear monocytosis was seen in newly diagnosed GCA and PMR patients caused by elevated numbers of classical monocytes. Prednisone treatment suppressed numbers of non-classical monocytes. Both chemokine CX3CL1 and CCL2 were highly expressed in the TAB. Most macrophages in the TAB of GCA patients expressed non-classical monocyte markers CD16 and CX3CR1 whereas co-localisation of CD16 with classical monocyte marker CCR2 was infrequent. In conclusion, we report an altered distribution of monocyte subsets in both GCA and PMR patients. The majority of macrophages in TABs of GCA patients were CD68 + CD16 + CX3CR1 + CCR2- and thereby resembled the phenotype of non-classical monocytes.