Longitudinal immune cell monitoring identified CD14++CD16+intermediate monocyte as a marker of relapse in patients with ANCA-associated vasculitis
Longitudinal immune cell monitoring identified CD14++CD16+intermediate monocyte as a marker of relapse in patients with ANCA-associated vasculitis
复制标题
DOI：
10.1186/s13075-020-02234-8
复制
发表时间：
2020-06-16
影响因子：
4.9
通讯作者：
Takeuchi, Tsutomu
中科院分区：
文献类型：
--
作者：
Matsumoto, Kotaro;Suzuki, Katsuya;Takeuchi, Tsutomu
背景抗中性粒细胞胞浆抗体(ANCA)相关性小血管炎(AAV)是一种影响中小血管的自身免疫性疾病。尽管治疗方法有所改进，但患者往往会复发。目前尚不清楚免疫细胞如何参与血管炎的发展，以及它们在治疗过程中如何波动。在这项研究中，我们旨在通过全面的免疫表型鉴定AAV患者中与疾病复发相关的免疫亚群和血清细胞因子。方法我们回顾了庆应大学医院2015年1月至2019年2月新诊断为甲型肝炎病毒的29例患者，并按时间顺序随访至52周。用流式细胞仪分析外周血中T细胞、B细胞、单核细胞和粒细胞的数量。采用电化学发光法测定血清细胞因子水平。从患者的记录中获得临床信息，并评估与免疫表型和血清细胞因子水平随时间变化的相关性。结果对29例AAV患者的161份样本在确诊时、治疗4、12、24、52周和主要复发时的免疫表型数据进行了全面的检测。复发患者的FACS分析显示CD14(++)CD16(+)中间单核细胞和浆细胞随疾病复发而改变，与治疗方案、ANCA状态或疾病表型无关。尤其是复发时CD14(++)CD16(+)中间单核细胞数量显著高于缓解期和健康对照组。血清细胞因子检测显示单核细胞来源的促炎细胞因子如IL-1β、IL-6、IL-8和肿瘤坏死因子-α的变化与疾病状态有关。结论AAV患者外周血中CD14(++)、CD16(+)中间单核细胞计数的时序性变化可作为病情复发的指标。
Background Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is an autoimmune disease that affects small- to medium-sized blood vessels. Despite treatments having been improved, patients often experience disease relapses. It remains unclear how the immune cells involve in the development of vasculitis and how they fluctuate over the course of treatment. In this study, we aimed to identify the immune subsets and serum cytokines associated with disease relapse by comprehensive immuno-phenotyping in AAV patients. Methods We reviewed consecutive patients (n = 29) from Keio University Hospital who had been newly diagnosed with AAV from January 2015 to February 2019 and chronologically followed until 52 weeks. Numbers of circulating T cells, B cells, monocytes, and granulocytes were analyzed by flow cytometry (FACS). Serum levels of cytokines were measured by electrochemiluminescence enzyme immunoassay. Clinical information was obtained from patients' records and association with time-course changes in immuno-phenotypes and serum levels of cytokines were assessed. Results Comprehensive immuno-phenotyping data from 161 samples from 29 AAV patients at diagnosis; at weeks 4, 12, 24, and 52 of treatment; and at time of major relapse were examined. FACS analysis from patients with relapse revealed that CD14(++)CD16(+)intermediate monocytes and plasma cells concomitantly changed associated with disease relapse, which were independent from treatment regimen, ANCA status, or disease phenotype. In particular, the number of CD14(++)CD16(+)intermediate monocytes at relapse was significantly higher than that in remission or in healthy controls. Serum cytokine measurement revealed that changes of monocyte-derived proinflammatory cytokines such as IL-1 beta, IL-6, IL-8, and TNF-alpha were associated with disease status. Conclusions Chronological changes in CD14(++)CD16(+)intermediate monocyte counts can be a marker of disease relapse in AAV patients.