Expression of Interleukin-32 in the Inflamed Arteries of Patients With Giant Cell Arteritis
Objective Giant cell (temporal) arteritis (GCA) is a vasculitis that mainly affects the large and medium arteries, especially the branches of the proximal aorta. Interleukin-32 (IL-32) is a recently described Th1 proinflammatory cytokine, and is mainly induced by interferon-γ (IFNγ), IL-1β, and tumor necrosis factor α (TNFα). This study was undertaken to investigate the expression and tissue distribution of IL-32 in artery biopsy specimens from patients with GCA. Methods Quantitative gene expression analysis of IL-32, IL-1β, TNFα, IFNγ, IL-6, and IL-27 was performed in artery biopsy specimens obtained from 18 patients with GCA and 15 controls. Immunohistochemistry analysis was performed to …
New insights into the pathogenesis of giant cell arteritis
Giant cell arteritis (GCA) is an inflammatory chronic disease occurring exclusively in elderly individuals. Until recently, the disease has been considered a unique disease resulting from the interaction in the walls of susceptible arteries, between an unknown infectious agents with local dendritic cells (DCs), activated CD4 T cells and effector macrophages. Recent evidence has shown that this view was too simplistic and has clarified many of the pathogenetic aspects of the disease. Many genetic studies recently published have identified different new genes, including cytokines, adhesion molecules and regulators of innate immunity, as crucial players in the development and progression of GC…
Ectopic expression of CXCL13, BAFF, APRIL and LT-ß is associated with artery tertiary lymphoid organs in giant cell arteritis
ObjectivesTo investigate whether artery tertiary lymphoid organs (ATLOs) are present in giant cell arteritis (GCA) and that their formation is associated with the ectopic expression of constitutive lymphoid tissue-homing chemokines.MethodsReverse transcriptase PCR, immunohistochemical and immunofluorescence analysis were used to determine the presence of ectopic ATLOs in GCA and the expression of chemokines/chemokine receptors and cytokines involved in lymphoneogenesis in the temporal artery samples obtained from 50 patients with GCA and 30 controls. The presence of lymphatic conduits, of follicular dendritic cells (FDCs) precursors and lymphoid tissue inducer cells was also investigated. F…
OP0193 Inflammation of adventitial nerves occurs in giant cell arteritis patients and it is characterized by inflammasomes, upr and autophagy activation
Background Vascular adventitia is a major site of immune surveillance and inflammatory cell trafficking and is the most complex compartment of the vessel wall comprising fibroblasts, dendritic cells and macrophages, progenitor cells, vasa vasorum, pericytes and adrenergic nerves. It has been proposed that activation of adventitial nerves and release of sensory neuropeptides from their peripheral terminals may leads to neurogenic inflammation. Giant cell arteritis (GCA) is an immune-mediated disease of unknown etiology in which the inflammatory process seems to start from the adventitia of affected arteries. Objectives aim of the study was to evaluate the occurrence of adventitial nerves inf…
Difference in the expression of IL-9 and IL-17 correlates with different histological pattern of vascular wall injury in giant cell arteritis
OBJECTIVE: GCA is a large- and medium-vessel arteritis characterized by a range of histological patterns of vascular wall injury. The aim of this study was to immunologically characterize the various histological patterns of GCA. METHODS: Thirty-five consecutive patients with biopsy-proven GCA and 15 normal controls were studied. IL-8, IL-9, IL-9R, IL-17, IL-4, TGF-β and thymic stromal lymphopoietin expression was evaluated by RT-PCR and immunohistochemistry on artery biopsy specimens. Confocal microscopy was used to characterize the phenotypes of IL-9-producing and IL-9R-expressing cells. Five additional patients who had received prednisone when the temporal artery biopsy was performed wer…
IL-33 is overexpressed in the inflamed arteries of patients with giant cell arteritis.
OBJECTIVE: To study the expression of interleukin (IL)-33 and to evaluate its relationship with macrophage polarisation in artery biopsy specimens from patients with giant cell arteritis (GCA). METHODS: IL-33, ST2, p-STAT-6 and perivascular IL-1 receptor-associated kinase 1 (p-IRAK1) tissue distribution was evaluated by immunohistochemistry. Inducible nitric oxide synthase and CD163 were also used by immunohistochemistry to evaluate the M1 and M2 polarisation, respectively. Quantitative gene expression analysis of IL-33, T-helper (Th)2-related transcription factor STAT6, Th2 cytokines (IL-4, IL-5, IL-25) and interferon (IFN)-γ was performed in artery biopsy samples obtained from 20 patients…
SAT0023 Artery Tertiary Lymphoid Organs Occur in Giant Cell Arteritis
Background Arteries are immuno-privileged sites. In advanced atherosclerotic lesions, however, adventitial lymphoid infiltrates, sometimes aggregated in lymphoid follicles (the so called artery tertiary lymphoid organs, ATLO), occur together with marked neoangiogenesis and lymphangiogenesis, and with the extensive induction of high endothelial venules. Objectives To investigate if tertiary lymphoid organs (TLO) are present in GCA and their formation is associated with the ectopic expression of constitutive lymphoid tissue-homing chemokines. Methods RT-PCR, immunohistochemical and immunofluorescence analysis were used to determine the presence of ectopic TLO in GCA and the expression of chem…
Increased expression of interleukin-22 in patients with giant cell arteritis
Objectives GCA is characterized by arterial remodelling driven by inflammation. IL-22 is an attractive cytokine which acts at the crosstalk between immune and stromal cells. We hypothesized that IL-22 might be induced in GCA and might be involved in disease pathogenesis. Methods Patients subjected to temporal artery biopsies (TABs) naive from therapy were enrolled: 27 biopsy-proven GCA, 8 biopsy-negative GCA, 21 biopsy-negative non-GCA patients. Expression of IL-22 was determined in TABs by immunohystochemistry, in plasma by ELISA, in peripheral blood mononuclear cells by real-time PCR and flow cytometry. Effects of IL-22 on viability and gene expression of primary cultures obtained from TA…
CD3 immunohistochemistry is helpful in the diagnosis of giant cell arteritis.
Objective. To evaluate whether CD3 staining performed routinely on temporal artery biopsy specimens might improve the sensitivity of temporal artery biopsy in patients with biopsy-negative GCA. Methods. Two hundred and seventy biopsies were considered for this study, stained with haematoxylin and eosin and with an anti-CD3 antibody. Results. The addition of CD3 staining modified the sensibility and the specificity of the histologic examination in 89.47 and 95.00%, respectively, with a positive and negative predictive values of 97.00 and 79.78%. Conclusion. The addition of CD3 immunostaining to the classic histologic evaluation is accompanied by a significant increase in the sensibility with…