Department of Medicine, Jagiellonian University Medical College, Krakow, Poland.
Clin Exp Rheumatol. 2011 Jan-Feb;29(1 Suppl 64):S23-34. Epub 2011 May 11.
Churg-Strauss syndrome (CSS) is a rare systemic vasculitis associated with eosinophilia and granuloma formation. The contribution of individual T-helper cell lineages in pathogenesis of CSS is unknown. We hypothesised that in CSS an imbalance of major effector T-cell subpopulations takes place, and is further influenced by the mode of treatment.
We investigated the immunophenotype, cytokine production and transcriptome profile in peripheral blood lymphocytes (PBL) from 19 patients with stable CSS (10 were treated with glucocorticoids alone (CSS/GC), 9 with steroids and other immunosuppressive drugs (CSS/IS)), and 13 healthy controls. Furthermore, serum IL-5 and CCR4-active chemokines (CCL17, CCL22) were measured in six patients with active disease and upon remission.
All CSS patients had decreased percentage of FoxP3+ regulatory T cells. In the CSS/GC group we found an increase in the Th17/Treg ratio and up-regulation of both Th2 and Th17 markers as evidenced by (1) over expression of Th2-related genes (GATA3, STAT6) in PBL, (2) elevated concentrations of serum IL-5 and CCL17, and (3) a concomitant increase in the number of Th17 cells, and secretion of IL-17A by stimulated PBL. The level of CCR4-active chemokines was increased in active-CSS, and correlated with blood eosinophilia. The combined treatment with steroids and other immunosuppressive drugs was associated with a significant decrease in both Th2-related chemokines and the number of Th17 cells.
Our results indicate that both Th2 and Th17 lineages are involved in the pathogenesis of CSS, while CCR4-active chemokines contribute to eosinophilia in the active disease. These phenomena are down regulated by immunosuppressive therapy.
变应性肉芽肿性血管炎（CSS）是一种罕见的系统性血管炎，与嗜酸性粒细胞增多和肉芽肿形成有关。个体辅助性 T 细胞谱系在 CSS 发病机制中的作用尚不清楚。我们假设在 CSS 中，主要效应 T 细胞亚群的失衡发生，并且进一步受到治疗方式的影响。
我们研究了 19 例稳定期 CSS 患者（10 例单独接受糖皮质激素治疗（CSS/GC），9 例接受糖皮质激素和其他免疫抑制剂治疗（CSS/IS））和 13 例健康对照者外周血淋巴细胞（PBL）的免疫表型、细胞因子产生和转录组谱。此外，在 6 例活动期和缓解期患者中测量了血清 IL-5 和 CCR4 活性趋化因子（CCL17、CCL22）。
所有 CSS 患者的 FoxP3+调节性 T 细胞百分比均降低。在 CSS/GC 组中，我们发现 Th17/Treg 比值增加，并且 Th2 和 Th17 标志物均上调，证据为（1）PBL 中 Th2 相关基因（GATA3、STAT6）过度表达，（2）血清 IL-5 和 CCL17 浓度升高，以及（3）Th17 细胞数量增加，以及刺激的 PBL 分泌 IL-17A。活动期 CSS 中 CCR4 活性趋化因子水平升高，并与血嗜酸性粒细胞增多相关。类固醇和其他免疫抑制剂联合治疗与 Th2 相关趋化因子和 Th17 细胞数量的显著减少相关。
我们的结果表明，Th2 和 Th17 谱系都参与了 CSS 的发病机制，而 CCR4 活性趋化因子有助于疾病活动期的嗜酸性粒细胞增多。这些现象通过免疫抑制治疗得到下调。
