RT Journal Article
SR Electronic
T1 Ectopic expression of CXCL13, BAFF, APRIL and LT-β is associated with artery tertiary lymphoid organs in giant cell arteritis
JF Annals of the Rheumatic Diseases
JO Ann Rheum Dis
FD BMJ Publishing Group Ltd and European League Against Rheumatism
SP 235
OP 243
DO 10.1136/annrheumdis-2016-209217
VO 76
IS 1
A1 Francesco Ciccia
A1 Aroldo Rizzo
A1 Rosario Maugeri
A1 Riccardo Alessandro
A1 Stefania Croci
A1 Giuliana Guggino
A1 Alberto Cavazza
A1 Stefania Raimondo
A1 Alessandra Cannizzaro
A1 Domenico Gerardo Iacopino
A1 Carlo Salvarani
A1 Giovanni Triolo
YR 2017
UL http://ard.bmj.com/content/76/1/235.abstract
AB Objectives To 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.Methods Reverse 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. Finally, expression of CXCL13, B cell activating factor (BAFF), a proliferation-inducing ligand (APRIL) and CCL21 by isolated myofibroblasts was evaluated before and after stimulation with Toll-like receptors (TLRs) agonists and cytokines.Results ATLOs were observed in the media layer of 60% of patients with GCA in close proximity to high endothelial venules and independently by the age of patients and the presence of atherosclerosis. ATLO formation was also accompanied by the expression of CXCL13, BAFF, a proliferation-inducing ligand (APRIL), lymphotoxin (LT)-β, interleukin (IL)-17 and IL-7, the presence of FDC precursors and of lymphoid conduits. Stimulation of myofibroblasts with TLR agonists and cytokines resulted in the upregulation of BAFF and CXCL13.Conclusions ATLOs occur in the inflamed arteries of patients with GCA possibly representing the immune sites where immune responses towards unknown arterial wall-derived antigens may be organised.