title: Increased IL-17A expression in temporal artery lesions is a predictor of sustained response to glucocorticoid treatment in patients with giant-cell arteritis.
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.
authors.affiliation: Vasculitis Research Unit, Department of Autoimmune Diseases, Hospital Clínic, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi iSunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Georgina
authors.initials: G
authors.lastname: Espígol-Frigolé
authors.forename: Marc
authors.initials: M
authors.lastname: Corbera-Bellalta
authors.forename: Ester
authors.initials: E
authors.lastname: Planas-Rigol
authors.forename: Ester
authors.initials: E
authors.lastname: Lozano
authors.forename: Marta
authors.initials: M
authors.lastname: Segarra
authors.forename: Ana
authors.initials: A
authors.lastname: García-Martínez
authors.forename: Sergio
authors.initials: S
authors.lastname: Prieto-González
authors.forename: José
authors.initials: J
authors.lastname: Hernández-Rodríguez
authors.forename: Josep M
authors.initials: JM
authors.lastname: Grau
authors.forename: Mahboob U
authors.initials: MU
authors.lastname: Rahman
authors.forename: Maria C
authors.initials: MC
authors.lastname: Cid
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005786:Gene Expression Regulation; D013700:Giant Cell Arteritis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011241:Prednisone / Q000627:therapeutic use*; D011379:Prognosis; D011446:Prospective Studies; D012074:Remission Induction; D050378:T-Lymphocytes, Regulatory; D013699:Temporal Arteries / Q000378:metabolism / Q000473:pathology*; D016896:Treatment Outcome
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D005938:Glucocorticoids; C508717:IL17A protein, human; D020381:Interleukin-17; D011241:Prednisone