Vasculitis Research Unit, Department of Autoimmune Diseases, Hospital Clínic, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi iSunyer (IDIBAPS), Barcelona, Spain.
Ann Rheum Dis. 2013 Sep 1;72(9):1481-7. doi: 10.1136/annrheumdis-2012-201836. Epub 2012 Sep 19.
Interleukin 17A (IL-17A) exerts pivotal proinflammatory functions in chronic inflammatory and autoimmune diseases.
To investigate IL-17A expression in temporal artery lesions from patients with giant-cell arteritis (GCA), and its relationship with disease outcome.
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.
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.
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.
白细胞介素 17A（IL-17A）在慢性炎症和自身免疫性疾病中发挥关键的促炎作用。
研究巨细胞动脉炎（GCA）患者颞动脉病变中 IL-17A 的表达及其与疾病结局的关系。
前瞻性评估 57 例经活检证实的 GCA 患者，进行 4.5 年（52-464 周）的治疗和随访。前瞻性记录复发、达到维持泼尼松剂量<10mg/天所需的时间（周）和完成泼尼松停药所需的时间（周）。采用实时定量 RT-PCR 检测所有患者和 19 例对照的颞动脉中 IL-17A mRNA 的表达。采用免疫组织化学/免疫荧光法评估 IL-17 蛋白表达。
与对照组相比，GCA 患者的颞动脉样本中 IL-17A 的表达显著增加（6.22±8.61 与 2.50±3.9 相对单位，p=0.016）。令人惊讶的是，IL-17A 表达较强的患者复发倾向较低，且治疗时间明显缩短（中位数 25 与 44 周达到<10mg 泼尼松/天，p=0.0079）。IL-17A 与 RORc 或 RORα 表达之间无相关性，这表明这些转录因子可能不完全反映 Th17 分化，除 Th17 细胞外，其他细胞可能对活动期患者的 IL-17 表达有贡献。因此，通过共聚焦显微镜鉴定出病变中的 FoxP3+IL-17A+细胞，并且在经治疗患者的标本中显著减少。
IL-17A 在 GCA 病变中表达增加，是对糖皮质激素治疗反应的预测因子。未经治疗的患者中 FoxP3+细胞对 IL-17A 产生的贡献表明，当糖皮质激素下调促炎细胞因子的产生时，诱导性 Tregs 可能有助于疾病缓解。
