Significant association between clinical characteristics and changes in peripheral immuno-phenotype in large vessel vasculitis
Significant association between clinical characteristics and changes in peripheral immuno-phenotype in large vessel vasculitis
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DOI：
10.1186/s13075-019-2068-7
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发表时间：
2019-12-30
影响因子：
4.9
通讯作者：
Takeuchi, Tsutomu
中科院分区：
文献类型：
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作者：
Matsumoto, Kotaro;Suzuki, Katsuya;Takeuchi, Tsutomu
背景：大血管血管炎是一种以中、大动脉肉芽肿性炎症为特征的血管炎。急性期反应物的临床评估通常用于诊断和监测疾病；然而，准确评估血管疾病的活动状态可能是困难的。在这项研究中，我们对免疫表型进行了全面的调查，以探索与临床特征相关的有用的生物标志物。方法：选择2016年5月至2019年5月来我所就诊的连续的新诊断左心室患者。检测循环T细胞、B细胞、自然杀伤细胞、树突状细胞、单核细胞和粒细胞的数量，并按时间顺序进行跟踪。结果：对20例LVV患者和健康对照组(HCS)各90例的免疫表型数据进行了比较。巨细胞动脉炎(GCA)和/或大动脉炎(TAK)患者外周血中辅助性T细胞(Th)、滤泡辅助性T细胞(Tfh)、CD8(+)T、CD14(++)CD16(+)单核细胞和中性粒细胞数量均高于HCS患者。其中，TAK组CD8(+)T细胞和CD8(+)Tem细胞数明显高于GCA组。值得注意的是，即使在缓解期，TAK患者的记忆CD4(+)和CD8(+)T细胞仍保持高水平。进一步分析发现，Th1、Th17和Tfh细胞的数量与GCA和TAK的疾病复发有关，CD8(+)T细胞的数量与TAK的复发有关。结论：外周免疫表型分析结果显示，GCA和TAK患者外周血中Th和Tfh细胞数量随病情变化而变化，而CD8(+)T细胞数量变化不明显，尤其是TAK患者。生物制剂治疗降低了患者Th和Tfh细胞的比例，但不降低CD8(+)T细胞的比例。时序免疫表型数据解释了GCA和TAK在治疗反应方面的差异，例如对生物制品的反应性。
Background: Large vessel vasculitis (LVV) is a type of vasculitis characterized by granulomatous inflammation of medium- and large-sized arteries. Clinical assessment of acute phase reactants has been conventionally used to diagnose and monitor diseases; however, accurate assessment of vascular disease activity status can be difficult. In this study, we investigated comprehensive immuno-phenotyping to explore useful biomarkers associated with clinical characteristics.Methods: Consecutive patients with newly diagnosed LVV who visited our institution between May 2016 and May 2019 were enrolled. The number of circulating T cells, B cells, natural killer cells, dendritic cells, monocytes, and granulocytes was examined and chronologically followed. Baseline and time-course changes in immunophenotyping associated with disease activity were assessed.Results: Comprehensive immuno-phenotyping data from 90 samples from each of 20 patients with LVV were compared with those from healthy controls (HCs). The number of helper T (Th), follicular helper T (Tfh), CD8(+) T, CD14(++) CD16(+) monocytes, and neutrophils were higher in patients with giant cell arteritis (GCA) and/or Takayasu arteritis (TAK) than in HCs. Among them, the number of CD8(+) T and CD8(+) Tem were higher in patients with TAK than in GCA. Notably, memory CD4(+) and CD8(+) T cells in patients with TAK remained high even in the remission phase. Further analysis revealed that the number of Th1, Th17, and Tfh cells was associated with disease relapse in GCA and TAK and that the number of CD8(+) T cells was associated with relapse in TAK. Th1, Th17, and Tfh cells decreased after treatment with biologic agents, while CD8(+) T cells did not.Conclusions: Our results from peripheral immuno-phenotyping analysis indicate that the numbers of Th and Tfh cells changed along with the disease condition in both GCA and TAK, while that of CD8(+) T cells did not, especially in TAK. Treatment with biologic agents decreased the proportion of Th and Tfh cells, but not CD8(+) T cells, in the patients. Chronological immuno-phenotyping data explained the difference in therapeutic response, such as reactivities against biologics, between GCA and TAK.