循环 PD-1 CD4 记忆 T 细胞和 PD-1 调节性 T 细胞比例增加与肺结节病对泼尼松的良好反应相关。
Increased proportions of circulating PD-1 CD4 memory T cells and PD-1 regulatory T cells associate with good response to prednisone in pulmonary sarcoidosis.
机构信息
Department of Pulmonary Medicine, Erasmus MC, University Medical Center, Doctor Molewaterplein 40, Rotterdam, 3015 GD, The Netherlands.
出版信息
Respir Res. 2024 May 7;25(1):196. doi: 10.1186/s12931-024-02833-y.
BACKGROUND
The treatment response to corticosteroids in patients with sarcoidosis is highly variable. CD4 T cells are central in sarcoid pathogenesis and their phenotype in peripheral blood (PB) associates with disease course. We hypothesized that the phenotype of circulating T cells in patients with sarcoidosis may correlate with the response to prednisone treatment. Therefore, we aimed to correlate frequencies and phenotypes of circulating T cells at baseline with the pulmonary function response at 3 and 12 months during prednisone treatment in patients with pulmonary sarcoidosis.
METHODS
We used multi-color flow cytometry to quantify activation marker expression on PB T cell populations in 22 treatment-naïve patients and 21 healthy controls (HCs). Pulmonary function tests at baseline, 3 and 12 months were used to measure treatment effect.
RESULTS
Patients with sarcoidosis showed an absolute forced vital capacity (FVC) increase of 14.2% predicted (± 10.6, p < 0.0001) between baseline and 3 months. Good response to prednisone (defined as absolute FVC increase of ≥ 10% predicted) was observed in 12 patients. CD4 memory T cells and regulatory T cells from patients with sarcoidosis displayed an aberrant phenotype at baseline, compared to HCs. Good responders at 3 months had significantly increased baseline proportions of PD-1CD4 memory T cells and PD-1 regulatory T cells, compared to poor responders and HCs. Moreover, decreased fractions of CD25 cells and increased fractions of PD-1 cells within the CD4 memory T cell population correlated with ≥ 10% FVC increase at 12 months. During treatment, the aberrantly activated phenotype of memory and regulatory T cells reversed.
CONCLUSIONS
Increased proportions of circulating PD-1CD4 memory T cells and PD-1 regulatory T cells and decreased proportions of CD25CD4 memory T cells associate with good FVC response to prednisone in pulmonary sarcoidosis, representing promising new blood biomarkers for prednisone efficacy.
TRIAL REGISTRATION
NL44805.078.13.
背景
结节病患者对皮质类固醇的治疗反应差异很大。CD4 T 细胞在结节病发病机制中起核心作用，其在外周血（PB）中的表型与疾病进程相关。我们假设结节病患者循环 T 细胞的表型可能与泼尼松治疗反应相关。因此，我们旨在比较初治肺结节病患者基线时循环 T 细胞的频率和表型与泼尼松治疗 3 个月和 12 个月时的肺功能反应。
方法
我们使用多色流式细胞术定量分析 22 例初治患者和 21 例健康对照者（HCs）PB T 细胞群的激活标志物表达。使用基线、3 个月和 12 个月的肺功能检查来衡量治疗效果。
结果
结节病患者的用力肺活量（FVC）绝对值较基线增加 14.2%（预测值±10.6，p<0.0001）。12 例患者对泼尼松的反应良好（定义为 FVC 绝对值增加≥10%预测值）。与 HCs 相比，结节病患者的 CD4 记忆 T 细胞和调节性 T 细胞在基线时表现出异常表型。与反应不佳者和 HCs 相比，3 个月时反应良好者的 PD-1CD4 记忆 T 细胞和 PD-1 调节性 T 细胞的基线比例显著增加。此外，CD4 记忆 T 细胞群中 CD25 细胞比例降低和 PD-1 细胞比例增加与 12 个月时 FVC 增加≥10%相关。在治疗过程中，记忆 T 细胞和调节性 T 细胞的异常激活表型逆转。
结论
循环 PD-1CD4 记忆 T 细胞和 PD-1 调节性 T 细胞比例增加以及 CD25CD4 记忆 T 细胞比例降低与肺结节病患者对泼尼松的 FVC 反应良好相关，代表了预测泼尼松疗效的有前途的新血液生物标志物。
试验注册
NL44805.078.13。
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