Abstract
IntroductionImmunological studies of giant cell arteritis (GCA) suggest that a triggering antigen of unknown nature could generate a specific immune response. We thus decided to detect autoantibodies directed against endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) in the serum of GCA patients and to identify their target antigens.MethodsSera from 15 GCA patients were tested in 5 pools of 3 patients' sera and compared to a sera pool from 12 healthy controls (HCs). Serum immunoglobulin G (IgG) reactivity was analysed by 2-D electrophoresis and immunoblotting with antigens from human umbilical vein ECs (HUVECs) and mammary artery VSMCs. Target antigens were identified by mass spectrometry.ResultsSerum IgG from GCA patients recognised 162 ± 3 (mean ± SD) and 100 ± 17 (mean ± SD) protein spots from HUVECs and VSMCs, respectively, and that from HCs recognised 79 and 94 protein spots, respectively. In total, 30 spots from HUVECs and 19 from VSMCs were recognised by at least two-thirds and three-fifths, respectively, of the pools of sera from GCA patients and not by sera from HCs. Among identified proteins, we found vinculin, lamin A/C, voltage-dependent anion-selective channel protein 2, annexin V and other proteins involved in cell energy metabolism and key cellular pathways. Ingenuity pathway analysis revealed that most identified target antigens interacted with growth factor receptor-bound protein 2.ConclusionsIgG antibodies to proteins in the proteome of ECs and VSMCs are present in the sera of GCA patients and recognise cellular targets that play key roles in cell biology and maintenance of homeostasis. Their potential pathogenic role remains to be determined.
Highlights
Immunological studies of giant cell arteritis (GCA) suggest that a triggering antigen of unknown nature could generate a specific immune response
Patients Serum samples were obtained from 15 patients who fulfilled the American College of Rheumatology (ACR) criteria for GCA [4] and 33 patients with anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis who fulfilled the ACR and the Chapel Hill criteria used as vasculitis controls, with the control group comprising 15 patients with Wegener’s granulomatosis (WG), 9 with Churg-Strauss syndrome (CSS) and 9 with microscopic polyangiitis (MPA) [18]
One-dimensional immunoblotting of immunoglobulin G (IgG) reactivity against vascular smooth muscle cell (VSMC) protein extracts One-dimensional immunoblots of IgG reactivity were analysed with VSMC protein extracts in sera from patients with GCA; control patients with ANCA-associated vasculitis, including those with WG, MPA and CSS; and healthy control (HC)
Summary
Immunological studies of giant cell arteritis (GCA) suggest that a triggering antigen of unknown nature could generate a specific immune response. We decided to detect autoantibodies directed against endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) in the serum of GCA patients and to identify their target antigens. GCA does not occur in GCA is an inflammatory condition of unknown origin characterised by the presence of giant cells and a remodelling process in the arterial wall [6]. In patients with GCA, an immune-mediated reaction is suspected to be triggered by an antigen of unknown origin, either microbial or a self-antigen, that could be presented to T cells by dendritic cells [7]. Macrophages and giant cells stimulated by interferon-g (IFN-g) play a major role in the disruption of the elastic lamina and the remodelling of vessel walls. In the adventitia, macrophages produce proinflammatory cytokines such as interleukin 1 (IL-1) and IL-6, whereas in the media and intima they contribute to arterial injury by producing metalloproteinases and nitric oxide [6,8,9]
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