Involvement of Monocyte Subsets in the Immunopathology of Giant Cell Arteritis

Abstract

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 (CD14brightCD16neg) and the more pro-inflammatory, intermediate (CD14brightCD16+) and non-classical (CD14dimCD16+) 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.

Differences in clinical manifestations and prognosis of Chinese giant cell arteritis patients with or without polymyalgia rheumatica

“…Although this was a retrospective study and most cases lacked data of peripheral blood lymphocyte subtype count, the lymphocyte count improved remarkably after treatment, which was in agreement with the previous studies. Sleen et al [23] indicated that peripheral blood monocyte count of GCA and PMR patients was higher than normal and decreased after treatment, which was similar to our findings. Some markers (such as matrix metalloproteinase-3, or small-vessel vasculitis and vasa vasorum vasculitis were observed in pathology) could be applied for predicting the presence of PMR or PMR-related symptoms in GCA patients [24,25].…”

Review: What Is the Current Evidence for Disease Subsets in Giant Cell Arteritis?

“…Th1 and CD8+ T cells are attracted by CXCL9 and CXCL10 , and Th17 cells are attracted by CCL20 . Monocytes enter the arterial wall under the influence of CCL2 and CX3CL1 , after which these cells differentiate into proinflammatory macrophages. B cells may migrate toward CCL20 and CXCL13 gradients in the arterial wall .…”

Distinct macrophage phenotypes skewed by local granulocyte macrophage colony‐stimulating factor (GM‐CSF) and macrophage colony‐stimulating factor (M‐CSF) are associated with tissue destruction and intimal hyperplasia in giant cell arteritis

“…These monocytes differentiate into macrophages upon entering the tissue. 1,6 Some of the macrophages fuse and develop into multinucleated giant cells. 7 Macrophages in GCA lesions are derived from circulating monocytes, of which three subsets have been identified: classical CD14 high CD16 À cells, intermediate CD14 high CD16 + cells and nonclassical CD14 dim CD16 + cells.…”

“…Although macrophages are one of the dominant inflammatory cellular infiltrates in GCA lesions, 6,[16][17][18][19] little is known about their phenotypic heterogeneity and spatial distribution within the affected vessel wall. We hypothesised that within GCA lesions, distinct macrophage phenotypes are associated with distinct functions and lesion morphology, dictated by local GM-CSF and M-CSF production.…”