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.
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: Chie Miyabe; Yoshishige Miyabe; Klemen Strle; Nancy D Kim; John H Stone; Andrew D Luster; Sebastian Unizony Journal: Ann Rheum Dis Date: 2016-12-07 Impact factor: 19.103
Authors: Kornelis S M van der Geest; Maria Sandovici; Pieter H Nienhuis; Riemer H J A Slart; Peter Heeringa; Elisabeth Brouwer; William F Jiemy Journal: Front Med (Lausanne) Date: 2022-06-06
Authors: Dan Pugh; Maira Karabayas; Neil Basu; Maria C Cid; Ruchika Goel; Carl S Goodyear; Peter C Grayson; Stephen P McAdoo; Justin C Mason; Catherine Owen; Cornelia M Weyand; Taryn Youngstein; Neeraj Dhaun Journal: Nat Rev Dis Primers Date: 2022-01-06 Impact factor: 65.038
Authors: F David Carmona; Sarah L Mackie; Jose-Ezequiel Martín; John C Taylor; Augusto Vaglio; Stephen Eyre; Lara Bossini-Castillo; Santos Castañeda; Maria C Cid; José Hernández-Rodríguez; Sergio Prieto-González; Roser Solans; Marc Ramentol-Sintas; M Francisca González-Escribano; Lourdes Ortiz-Fernández; Inmaculada C Morado; Javier Narváez; José A Miranda-Filloy; Lorenzo Beretta; Claudio Lunardi; Marco A Cimmino; Davide Gianfreda; Daniele Santilli; Giuseppe A Ramirez; Alessandra Soriano; Francesco Muratore; Giulia Pazzola; Olga Addimanda; Cisca Wijmenga; Torsten Witte; Jan H Schirmer; Frank Moosig; Verena Schönau; Andre Franke; Øyvind Palm; Øyvind Molberg; Andreas P Diamantopoulos; Simon Carette; David Cuthbertson; Lindsy J Forbess; Gary S Hoffman; Nader A Khalidi; Curry L Koening; Carol A Langford; Carol A McAlear; Larry Moreland; Paul A Monach; Christian Pagnoux; Philip Seo; Robert Spiera; Antoine G Sreih; Kenneth J Warrington; Steven R Ytterberg; Peter K Gregersen; Colin T Pease; Andrew Gough; Michael Green; Lesley Hordon; Stephen Jarrett; Richard Watts; Sarah Levy; Yusuf Patel; Sanjeet Kamath; Bhaskar Dasgupta; Jane Worthington; Bobby P C Koeleman; Paul I W de Bakker; Jennifer H Barrett; Carlo Salvarani; Peter A Merkel; Miguel A González-Gay; Ann W Morgan; Javier Martín Journal: Am J Hum Genet Date: 2015-03-26 Impact factor: 11.025
Authors: Sebastian H Unizony; Bhaskar Dasgupta; Elena Fisheleva; Lucy Rowell; Georg Schett; Robert Spiera; Jochen Zwerina; Olivier Harari; John H Stone Journal: Int J Rheumatol Date: 2013-04-07
Authors: A Serrano; A Márquez; S L Mackie; F D Carmona; R Solans; J A Miranda-Filloy; J Hernández-Rodríguez; M C Cid; S Castañeda; I C Morado; J Narváez; R Blanco; B Sopeña; M J García-Villanueva; J Monfort; N Ortego-Centeno; A Unzurrunzaga; B Marí-Alfonso; J Sánchez Martín; E de Miguel; C Magro; E Raya; N Braun; J Latus; O Molberg; B A Lie; F Moosig; T Witte; A W Morgan; M A González-Gay; J Martín Journal: Ann Rheum Dis Date: 2013-08-14 Impact factor: 19.103