Szczeklik Wojciech, Jakieła Bogdan, Wawrzycka-Adamczyk Katarzyna, Sanak Marek, Hubalewska-Mazgaj Magdalena, Padjas Agnieszka, Surmiak Marcin, Szczeklik Katarzyna, Sznajd Jan, Musiał Jacek
Department of Medicine, Jagiellonian University Medical College, Krakow, Poland.
Department of Integrated Dentistry, Jagiellonian University Medical College, Krakow, Poland.
Eur J Immunol. 2017 Apr;47(4):724-733. doi: 10.1002/eji.201646810. Epub 2017 Feb 27.
The objective of our study was to evaluate the T-helper (Th) and regulatory T (Treg) cell profile in ANCA-positive granulomatosis with polyangiitis (GPA) and its relation to disease activity. In a prospective study, we studied two groups of GPA patients: (i) disease flare (active-GPA, BVAS>6, n = 19), (ii) sustained remission (≥ 1-year prior enrollment, inactive-GPA, BVAS = 0, n = 18). 24 age-sex matched healthy subjects served as controls. Active-GPA patients were followed for 6 months and reevaluated during remission (early remission; n = 13). We analyzed subsets of Th-cells (flow cytometry), production of signature cytokines by in vitro stimulated lymphocytes, and broad spectrum of serum cytokines (Luminex). In all GPA patients we observed expansion of effector Th17 cells, and increased production of IL-17A by in vitro stimulated T cells, as compared to controls. Disease flare was characterized by marked reduction in Treg cells, whereas in sustained remission we showed expansion of both Treg and Th2 subset. Finally, analyzing the cytokine profile, we identified CCL23 and LIGHT, as potential biomarkers of active disease. We conclude that in GPA, expansion of Treg and Th2 lymphocytes in parallel to increased Th17 response is a characteristic feature of sustained remission. In contrast, Treg cells are markedly decreased in disease flare.
我们研究的目的是评估抗中性粒细胞胞浆抗体（ANCA）阳性的肉芽肿性多血管炎（GPA）患者的辅助性T（Th）细胞和调节性T（Treg）细胞谱及其与疾病活动的关系。在一项前瞻性研究中，我们研究了两组GPA患者：（i）疾病发作（活动期GPA，BVAS>6，n = 19），（ii）持续缓解（入组前≥1年，非活动期GPA，BVAS = 0，n = 18）。24名年龄和性别匹配的健康受试者作为对照。对活动期GPA患者随访6个月，并在缓解期（早期缓解；n = 13）进行重新评估。我们分析了Th细胞亚群（流式细胞术）、体外刺激淋巴细胞产生的标志性细胞因子以及血清细胞因子的广谱分析（Luminex）。与对照组相比，在所有GPA患者中我们观察到效应性Th17细胞扩增，以及体外刺激的T细胞产生的IL-17A增加。疾病发作的特征是Treg细胞显著减少，而在持续缓解期我们发现Treg和Th2亚群均扩增。最后，通过分析细胞因子谱，我们确定CCL23和LIGHT作为活动期疾病的潜在生物标志物。我们得出结论，在GPA中，Treg和Th2淋巴细胞的扩增与Th17反应增加同时出现是持续缓解的特征。相比之下，在疾病发作期Treg细胞显著减少。
