Increased IL-17A expression in temporal artery lesions is a predictor of sustained response to glucocorticoid treatment in patients with giant-cell arteritis.

Authors: Espigol-Frigole, G  Corbera-Bellalta, M  Planas-Rigol, E  Lozano, E  Segarra, M  Garcia-Martinez, A  Prieto-Gonzalez, S  Hernandez-Rodriguez, J  Grau, JM  Rahman, MU  Cid, MC 
Citation: Espigol-Frigole G, etal., Ann Rheum Dis. 2013 Sep 1;72(9):1481-7. doi: 10.1136/annrheumdis-2012-201836. Epub 2012 Sep 19.
Pubmed: (View Article at PubMed) PMID:22993227
DOI: Full-text: DOI:10.1136/annrheumdis-2012-201836

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 RORalpha 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.

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CRRD ID: 8698666
Created: 2014-08-12
Species: All species
Last Modified: 2014-08-12
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.