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Ectopic expression of CXCL13, BAFF, APRIL and LT-β is associated with artery tertiary lymphoid organs in giant cell arteritis
  1. Francesco Ciccia1,
  2. Aroldo Rizzo2,
  3. Rosario Maugeri3,
  4. Riccardo Alessandro4,
  5. Stefania Croci5,
  6. Giuliana Guggino1,
  7. Alberto Cavazza6,
  8. Stefania Raimondo4,
  9. Alessandra Cannizzaro2,
  10. Domenico Gerardo Iacopino3,
  11. Carlo Salvarani7,
  12. Giovanni Triolo1
  1. 1Dipartimento Biomedico di Medicina Interna e Specialistica, Sezione di Reumatologia, Università degli Studi di Palermo, Palermo, Italy
  2. 2Dipartimento di Oncoematologia, Sezione di Anatomia Patologica, Azienda Ospedaliera Ospedali riuniti Villa Sofia Cervello, Palermo, Italy
  3. 3Dipartimento di Emergenze, Urgenze e Neuroscienze Cliniche, Università di Palermo, Palermo, Italy
  4. 4Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi, Università di Palermo, Palermo, Italy
  5. 5Clinical Immunology, Allergy and Advanced Biotechnologies Unit, Arcispedale Santa Maria Nuova, IRCCS, Reggio Emilia, Italy
  6. 6Pathology Unit, Arcispedale Santa Maria Nuova, IRCCS, Reggio Emilia, Italy
  7. 7Unità operativa di Reumatologia, Arcispedale S. Maria Nuova-IRCCS, Reggio Emilia, Italy
  1. Correspondence to Professor Giovanni Triolo, Dipartimento Biomedico di Medicina Interna e Specialistica, Sezione di Reumatologia, Piazza delle Cliniche 2, 90127 Palermo, Italy; giovanni.triolo{at}unipa.it

Abstract

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.

  • Giant Cell Arteritis
  • Chemokines
  • Cytokines

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Footnotes

  • Handling editor Tore K Kvien

  • Contributors CS and GT shared co-senior authorship. Study design: FC, AR, CS and GT. Acquisition of data: RM, RA, SC, GG, AC, SR, AC and DGI. Analysis and interpretation of data: FC, AR, CS, GT, SC, RM, RA, SC, GG, SR and DGI. Manuscript preparation: FC, CS and GT. Statistical analysis: FC and AC. Overall supervision: GT, CS.

  • Funding This study was in part supported by a grant of Ministero dell'Istruzione, dell'Università e della ricerca Scientifica from Italy

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval University of Palermo.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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