Unsupervised Clustering Reveals Sarcoidosis Phenotypes Marked by a Reduction in Lymphocytes Relate to Increased Inflammatory Activity on 18FDG-PET/CT

Frontiers in Medicine

article

Christen Vagts¹  David L. Perkins²  Patricia W. Finn¹  Nadera J. Sweiss¹  Christian Ascoli¹  Dustin R. Fraidenburg¹  Robert P. Baughman⁴  Yue Huang¹  Russell Edafetanure-Ibeh¹  Samreen Ahmed³  Benjamin Levin⁵  Yang Lu⁷ 

[1] Division of Pulmonary, Department of Medicine, University of Illinois at Chicago, United States;Division of Nephrology, Department of Medicine, University of Illinois at Chicago, United States;Division of Rheumatology, Department of Medicine, University of Illinois at Chicago, United States;Department of Internal Medicine, University of Cincinnati Medical Center, United States;Division of Cardiology, Department of Medicine, College of Medicine, University of Illinois at Chicago, United States;Jesse Brown VA Medical Center, United States;Division of Diagnostic Imaging, Department of Nuclear Medicine, The University of Texas MD Anderson Cancer Center, United States

关键词: sarcoidosis;    lymphopenia;    18FDG-PET/CT;    immunopathogenesis;    cluster analysis;    phenotype;   

DOI  :  10.3389/fmed.2021.595077

学科分类：社会科学、人文和艺术（综合）

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

CC BY