Unsupervised Clustering Reveals Sarcoidosis Phenotypes Marked by a Reduction in Lymphocytes Relate to Increased Inflammatory Activity on 18FDG-PET/CT.
Unsupervised Clustering Reveals Sarcoidosis Phenotypes Marked by a Reduction in Lymphocytes Relate to Increased Inflammatory Activity on 18FDG-PET/CT.
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无监督聚类揭示结节病表型特征为淋巴细胞减少与18FDG-PET/CT上炎症活性增加相关
DOI：
10.3389/fmed.2021.595077
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发表时间：
2021
影响因子：
3.9
通讯作者：
Sweiss NJ
中科院分区：
文献类型：
--
作者：
Vagts C;Ascoli C;Fraidenburg DR;Baughman RP;Huang Y;Edafetanure-Ibeh R;Ahmed S;Levin B;Lu Y;Perkins DL;Finn PW;Sweiss NJ
简介：结节病是一种以肉芽肿性炎症为特征的辅助性T细胞介导的疾病。我们假设结节病的各种特征的无监督聚类将建立与18FDG-PET/CT测量的炎症活性相关的表型。我们的目标是确定能够区分簇的独特特征，并随后检查与FDG亲合力的关系，以证实其作为结节病炎症标志物的潜在用途。研究方法：我们进行了一项回顾性研究，研究对象为58名在伊利诺伊大学Bernie Mac结节病中心和肺部健康中心接受18FDG-PET/CT扫描的经活检证实的结节病患者，这些患者主要是非洲裔美国人。人口统计学、治疗学、放射学和实验室数据用于无监督聚类分析以确定结节病表型。确定了簇之间的关联，其定义特征和18 FDG-PET/CT的定量测量。还研究了这些特征作为18FDG-PET/CT炎症活性标志物的相关性。结果如下：聚类确定了三种不同的表型：（1）主要是非洲裔美国人的集群与慢性，静止的疾病，（2）主要是非洲裔美国人的集群与升高的传统炎症标志物，先进的肺部疾病和胸外参与，和（3）主要是白人集群的特点是减少淋巴细胞计数和急性疾病。与慢性静止簇相比，簇2和3由18FDG-PET/CT上显著更大的FDG亲合力定义。尽管18FDG-PET/CT上的炎症活性相似地增加，但聚类2和聚类3在胸外FDG亲合力和循环淋巴细胞谱（特别是CD 4 + T细胞）方面不同。值得注意的是，绝对淋巴细胞计数和CD 4 + T细胞计数被发现预测18 FDG-PET/CT炎症活动的受试者工作曲线分析，曲线下面积分别为69.2%和73.42%。结论：利用聚类分析，三种不同的结节病的表型被确定为在种族，疾病慢性和炎症的血清学标志物的显着变化。这些表型显示不同水平的循环炎性细胞。此外，淋巴细胞（特别是CD 4 + T细胞）的减少与18 FDG-PET/CT的活性显著相关。尽管需要进一步研究，但这些发现表明外周淋巴细胞计数可能被认为是结节病表型的决定因素和18 FDG-PET/CT上活动性炎症的指标。
Introduction: Sarcoidosis is a T-helper cell mediated disease characterized by granulomatous inflammation. We posited that unsupervised clustering of various features in sarcoidosis would establish phenotypes associated with inflammatory activity measured by 18FDG-PET/CT. Our goal was to identify unique features capable of distinguishing clusters and subsequently examine the relationship with FDG avidity to substantiate their potential use as markers for sarcoidosis inflammation. Methods: We performed a retrospective study of a diverse, but primarily African American, cohort of 58 subjects with biopsy proven sarcoidosis followed at the University of Illinois Bernie Mac Sarcoidosis Center and Center for Lung Health who underwent 18FDG-PET/CT scan. Demographic, therapeutic, radiographic, and laboratory data were utilized in unsupervised cluster analysis to identify sarcoidosis phenotypes. The association between clusters, their defining features, and quantitative measurements on 18FDG-PET/CT was determined. The relevance of these features as markers of 18FDG-PET/CT inflammatory activity was also investigated. Results: Clustering determined three distinct phenotypes: (1) a predominantly African American cluster with chronic, quiescent disease, (2) a predominantly African American cluster with elevated conventional inflammatory markers, advanced pulmonary disease and extrathoracic involvement, and (3) a predominantly Caucasian cluster characterized by reduced lymphocyte counts and acute disease. In contrast to the chronic quiescent cluster, Clusters 2 and 3 were defined by significantly greater FDG avidity on 18FDG-PET/CT. Despite similarly increased inflammatory activity on 18FDG-PET/CT, Clusters 2, and 3 differed with regards to extrathoracic FDG avidity and circulating lymphocyte profiles, specifically CD4+ T-cells. Notably, absolute lymphocyte counts and CD4+ T-cell counts were found to predict 18FDG-PET/CT inflammatory activity by receiver operating curve analysis with a 69.2 and 73.42% area under the curve, respectively. Conclusions: Utilizing cluster analysis, three distinct phenotypes of sarcoidosis were identified with significant variation in race, disease chronicity, and serologic markers of inflammation. These phenotypes displayed varying levels of circulating inflammatory cells. Additionally, reduction in lymphocytes, specifically CD4+ T-cells, was significantly related to activity on 18FDG-PET/CT. Though future studies are warranted, these findings suggest that peripheral lymphocyte counts may be considered a determinant of sarcoidosis phenotypes and an indicator of active inflammation on 18FDG-PET/CT.
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10.1007/s00259-017-3690-8
发表时间：
2017-08
影响因子：
9.1
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10.1164/rccm.202002-0251st
发表时间：
2020-04-15
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