Editorial: Lymphocyte Highs and Lows With Baricitinib.
Editorial: Lymphocyte Highs and Lows With Baricitinib.
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社论：Baricitinib 的淋巴细胞高点和低点。
DOI：
10.1002/art.40681
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Rao,DeepakA
中科院分区：
文献类型：
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作者：
Rao,DeepakA
JAK 抑制剂的出现为治疗类风湿性关节炎 (RA) 提供了一套强大的新型免疫调节剂。 JAK 抑制剂与 Janus 激酶 (JAK) 结合并干扰其功能，JAK 介导多种细胞因子和生长因子受体下游的信号传导 (1)。鉴于 JAK 抑制可能影响多种细胞因子，因此确定这些分子在患者体内发挥的主要免疫作用非常重要。在本期《关节炎和风湿病学》中，Tanaka 及其同事使用来自 3 项 3 期随机对照试验的数据描述了 baricitinib 引起的循环淋巴细胞群的变化 (2)。通过检查 2000 多名患者的淋巴细胞群变化，其中一些患者被随访了 2 年，作者提供了一组可靠的观察结果，可以与其他 JAK 抑制剂的经验进行比较，并可以深入了解巴瑞克替尼对免疫细胞稳态的影响。随机、安慰剂对照试验为建立相关免疫学分析提供了强大的基础设施。可以在治疗开始之前和之后获取血样，并且可以在整个试验过程中纵向收集血样，以确定治疗随时间推移引起的变化（图1）。虽然此类研究中经常采用血清中细胞因子的测量，但对循环免疫细胞本身的详细评估可以提供个体患者中最活跃的免疫细胞群和途径的更高分辨率视图 (3)。通过流式细胞术进行免疫细胞表型分析可以量化许多具有不同功能的白细胞群，并有可能识别受药物治疗强烈影响的细胞群 (4)。然后，这些细胞群可以作为候选细胞，可以作为药物作用机制中潜在的重要靶标进行评估。此外，还可以挖掘免疫表型数据来寻找预测治疗或不良事件反应的细胞生物标志物。
The advent of JAK inhibitors has provided a powerful new set of immunomodulatory agents to treat rheumatoid arthritis (RA). JAK inhibitors bind to and interfere with the function of Janus kinases (JAKs), which mediate signaling downstream of multiple cytokine and growth factor receptors (1). Given the wide range of cytokines that JAK inhibition can potentially influence, it is important to establish the dominant immunologic effects that these molecules exert in patients. In this issue of Arthritis and Rheumatology, Tanaka and colleagues describe the changes in circulating lymphocyte populations induced by baricitinib using data from 3 Phase 3 randomized controlled trials (2). By examining alterations in lymphocyte populations in over 2000 patients, with some patients followed for 2 years, the authors provide a robust set of observations that can be compared to experience with other JAK inhibitors and can yield insights into the effects of baricitinib on immune cell homeostasis.Randomized, placebo-controlled trials provide a powerful infrastructure upon which to build correlative immunologic analyses. Blood samples can be obtained before and after initiation of therapy and can be collected longitudinally throughout the trial to determine changes induced by therapy over time (Figure 1). While measurements of cytokines in serum have been frequently employed in such studies, detailed assessments of the circulating immune cells themselves may provide a higher resolution view of the most active immune cell populations and pathways in individual patients (3). Immune cell phenotyping by flow cytometry can quantify many leukocyte populations with diverse functions and has the potential to identify cell populations that are strongly influenced by drug therapy (4). These cell populations then serve as candidates that can be evaluated as potentially important targets in the mechanism of action of the drug. In addition, immunophenotyping data can be mined for cellular biomarkers that predict response to therapy or adverse events.