Department of Pulmonary Medicine, Erasmus MC, University Medical Center, Doctor Molewaterplein 40, Rotterdam, 3015 GD, The Netherlands.
Respir Res. 2024 May 7;25(1):196. doi: 10.1186/s12931-024-02833-y.
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.
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.
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.
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.
NL44805.078.13.
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。
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。
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。
NL44805.078.13。
