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Increased IL-17A expression in temporal artery lesions is a predictor of sustained response to glucocorticoid treatment in patients with giant-cell arteritis
  1. Georgina Espígol-Frigolé1,
  2. Marc Corbera-Bellalta1,
  3. Ester Planas-Rigol1,
  4. Ester Lozano1,
  5. Marta Segarra1,
  6. Ana García-Martínez2,
  7. Sergio Prieto-González1,
  8. José Hernández-Rodríguez1,
  9. Josep M Grau3,
  10. Mahboob U Rahman4,5,
  11. Maria C Cid1
  1. 1Vasculitis Research Unit, Department of Autoimmune Diseases, Hospital Clínic, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi iSunyer (IDIBAPS), Barcelona, Spain
  2. 2Vasculitis Research Unit, Department of Emergency Medicine, Hospital Clínic, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi iSunyer (IDIBAPS), Barcelona, Spain
  3. 3Department of Internal Medicine, Hospital Clínic, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi iSunyer (IDIBAPS), Barcelona, Spain
  4. 4University of Pennsylvania Medical School, Collegeville, Pennsylvania, USA
  5. 5Department of Medical Affairs, Inflammation, Pfizer Inc., Collegeville, Pennsylvania, USA
  1. Correspondence to Dr Maria C Cid, MD, Vasculitis Research Unit, Department of Systemic Autoimmune Diseases, Hospital Clínic, University of Barcelona, Institut d'Investigacions Biomediques August Pi Sunyer (IDIBAPS), Villarroel 170, Barcelona 08036, Spain; mccid{at}clinic.ub.es

Abstract

Background Interleukin 17A (IL-17A) exerts pivotal proinflammatory functions in chronic inflammatory and autoimmune diseases.

Objective To investigate IL-17A expression in temporal artery lesions from patients with giant-cell arteritis (GCA), and its relationship with disease outcome.

Methods Fifty-seven patients with biopsy-proven GCA were prospectively evaluated, treated and followed for 4.5 years (52–464 weeks). Relapses, time (weeks) required to achieve a maintenance prednisone dose <10 mg/day, and time (weeks) to complete prednisone withdrawal were prospectively recorded. IL-17A mRNA was measured by real-time quantitative RT-PCR in temporal arteries from all patients and 19 controls. IL-17 protein expression was assessed by immunohistochemistry/immunofluorescence.

Results IL-17A expression was significantly increased in temporal artery samples from GCA patients compared with controls (6.22±8.61 vs 2.50±3.9 relative units, p=0.016). Surprisingly, patients with strong IL-17A expression tended to experience less relapses, and required significantly shorter treatment periods (median 25 vs 44 weeks to achieve <10 mg prednisone/day, p=0.0079). There was no correlation between IL-17A and RORc or RORα expression suggesting that these transcription factors may not exclusively reflect Th17 differentiation, and that cells other than Th17 cells might contribute to IL-17 expression in active patients. Accordingly, FoxP3+IL-17A+ cells were identified in lesions by confocal microscopy and were dramatically reduced in specimens from treated patients.

Conclusions IL-17A expression is increased in GCA lesions, and is a predictor of response to glucocorticoid treatment. The contribution of FoxP3+ cells to IL-17A production in untreated patients suggests that induced-Tregs may facilitate disease remission when proinflammatory cytokine production is downregulated by glucocorticosteroids.

  • Systemic vasculitis
  • Giant Cell Arteritis
  • Cytokines
  • Disease Activity
  • Inflammation

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