Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Clinical Research Management Center, Nagoya City University Hospital, Nagoya, Japan.
PLoS One. 2019 Nov 20;14(11):e0215192. doi: 10.1371/journal.pone.0215192. eCollection 2019.
T-helper (Th)17.1 cells exhibit high pathogenicity in inflammatory diseases. This study aimed to identify the changes in the proportions of Th subsets, including Th17.1, which are associated with abatacept treatment response in Japanese patients with rheumatoid arthritis. On the basis of the results, we assessed whether Th17.1 is a potential cellular biomarker. Multicolor flow cytometry was used to determine the circulating Th subsets among CD4+ T lymphocytes in 40 patients with rheumatoid arthritis before abatacept treatment. All the patients received abatacept treatment for 24 weeks; changes in disease activity score, including 28-joint count C-reactive protein, and responsiveness indicated by other indices to abatacept treatment were evaluated according the European League Against Rheumatism criteria (good and moderate responders and nonresponders). The correlation between the abatacept responses and the proportions of Th subsets (baseline) was analyzed. Logistic regression analysis with inverse probability weighting method was performed to calculate the odds ratio adjusted for patient characteristics. The proportion of baseline Th17.1 cells was significantly lower in patients categorized as good responders than in those categorized as non-good responders (moderate responders and nonresponders; p = 0.0064). The decrease in 28-joint count C-reactive protein after 24 weeks of abatacept therapy showed a significant negative correlation with the proportion of Th17.1 cells. The adjusted odds ratio for achieving good response in patients with baseline Th17.1 levels below the median value was 14.6 (95% confidence interval, 2.9-72.3; p = 0.0021) relative to that in the remaining patients. The proportion of Th17.1 cells at baseline is a good candidate for predicting abatacept treatment response in Japanese patients. These novel findings may represent a significant step in the pursuit of precision medicine.
辅助性 T 细胞(Th)17.1 细胞在炎症性疾病中具有高致病性。本研究旨在鉴定与类风湿关节炎日本患者接受阿巴西普治疗反应相关的 Th 亚群(包括 Th17.1)比例的变化。基于这些结果,我们评估了 Th17.1 是否是一种潜在的细胞生物标志物。采用多色流式细胞术在 40 例接受阿巴西普治疗前的类风湿关节炎患者的 CD4+T 淋巴细胞中确定循环 Th 亚群。所有患者均接受阿巴西普治疗 24 周;根据欧洲抗风湿病联盟(EULAR)标准(良好和中度反应者以及无反应者)评估疾病活动评分(包括 28 关节 C 反应蛋白)和对阿巴西普治疗的其他指标的反应性的变化。分析了阿巴西普治疗反应与 Th 亚群(基线)比例之间的相关性。采用逆概率加权法进行逻辑回归分析,以计算经患者特征调整的优势比。与非良好反应者(中度反应者和无反应者)相比,良好反应者的基线 Th17.1 细胞比例显著降低(p = 0.0064)。24 周阿巴西普治疗后 28 关节 C 反应蛋白的降低与 Th17.1 细胞比例呈显著负相关。基线 Th17.1 水平低于中位数的患者达到良好反应的调整后优势比为 14.6(95%置信区间,2.9-72.3;p = 0.0021),而其余患者的调整后优势比为 1。基线 Th17.1 细胞比例是预测日本患者阿巴西普治疗反应的良好候选标志物。这些新发现可能代表着精准医学的重要一步。