Abstract
ObjectiveB-cells are present in the inflamed arteries of giant cell arteritis (GCA) patients and a disturbed B-cell homeostasis is reported in peripheral blood of both GCA and the overlapping disease polymyalgia rheumatica (PMR). In this study, we aimed to investigate chemokine-chemokine receptor axes governing the migration of B-cells in GCA and PMR. MethodsWe performed Luminex screening assay for serum levels of B-cell related chemokines in treatment-naïve GCA (n = 41), PMR (n = 31) and age- and sex matched healthy controls (HC, n = 34). Expression of chemokine receptors on circulating B-cell subsets were investigated by flow cytometry. Immunohistochemistry was performed on GCA temporal artery (n = 14) and aorta (n = 10) and on atherosclerosis aorta (n = 10) tissue. ResultsThe chemokines CXCL9 and CXCL13 were significantly increased in the circulation of treatment-naïve GCA and PMR patients. CXCL13 increased even further after three months of glucocorticoid treatment. At baseline CXCL13 correlated with disease activity markers. Peripheral CXCR3+ and CXCR5+ switched memory B-cells were significantly reduced in both patient groups and correlated inversely with their complementary chemokines CXCL9 and CXCL13. At the arterial lesions in GCA, CXCR3+ and CXCR5+ B-cells were observed in areas with high CXCL9 and CXCL13 expression. ConclusionChanges in systemic and local chemokine and chemokine receptor pathways related to B-cell migration were observed in GCA and PMR mainly in the CXCL9-CXCR3 and CXCL13-CXCR5 axes. These changes can contribute to homing and organization of B-cells in the vessel wall and provide further evidence for an active involvement of B-cells in GCA and PMR.
Highlights
Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are frequently overlapping inflammatory diseases occurring at an older age [1]
Serum chemokine levels in giant cell arteritis (GCA) and PMR patients compared to healthy controls (HC)
CXCL13 was increased in both patient groups compared to HC and CXCL13 levels in PMR were significantly elevated compared to GCA (Fig. 1C)
Summary
Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are frequently overlapping inflammatory diseases occurring at an older age [1]. PMR is diagnosed in up to 60% of GCA patients [2,3], whereas the prevalence of GCA in PMR varies between 5 and 30% [4]. GCA is characterized by inflammation of the medium- and large arteries, while PMR is characterized by inflammation primarily of the synovial tissue of shoulders and hips. Dependent on which arteries are involved, GCA leads to cranial symptoms like headache (temporal artery; TA), or more systemic symptoms like weight loss and low-grade fever (aorta and its proximal branches) [5]. A complication of GCA is the formation of an aortic aneurysm. PMR is characterized by pain and stiffness mainly in the shoulder and hip girdle [2,3]
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