Single-Cell Mass Cytometry on Peripheral Blood Identifies Immune Cell Subsets Associated with Primary Biliary Cholangitis
Authors:
- Jin Sung JangJJJin Sung Jang
- Brian D JuranBJBrian D Juran
- Kevin Y. CunninghamKCKevin Y. Cunningham
- Vinod K. GuptaVGVinod K. Gupta
- YoungMin SonYSYoungMin Son
- Ju Dong YangJYJu Dong Yang
- Ahmad H. AliAAAhmad H. Ali
- Elizabeth Ann L. EnningaEEElizabeth Ann L. Enninga
- Jaeyun SungJSJaeyun Sung
- Konstantinos N. LazaridisKLKonstantinos N. Lazaridis
Preprint
Abstract
The relationship between Primary Biliary Cholangitis (PBC), a chronic cholestatic autoimmune liver disease, and the peripheral immune system remains to be fully understood. Herein, we performed the first mass cytometry (CyTOF)-based, immunophenotyping analysis of the peripheral immune system in PBC at single-cell resolution. CyTOF was performed on peripheral blood mononuclear cells (PBMCs) from PBC patients (n=33) and age-/sex-matched healthy controls (n=33) to obtain immune cell abundance and marker expression profiles. Hiearchical clustering methods were applied to identify immune cell types and subsets significantly associated with PBC. Subsets of gamma-delta T cells (CD3 + TCRgd + ), CD8 + T cells (CD3 + CD8 + CD161 + PD1 + ), and memory B cells (CD3 - CD19 + CD20 + CD24 + CD27 + ) were found to have lower abundance in PBC than in control. In contrast, higher abundance of subsets of monocytes and naïve B cells were observed in PBC compared to control. Furthermore, several naïve B cell (CD3 - CD19 + CD20 + CD24 - CD27 - ) subsets were significantly higher in PBC patients with cirrhosis (indicative of late-stage disease) than in those without cirrhosis. Alternatively, subsets of CD8 + CD161 + T cells and memory B cells were lower in abundance in cirrhotic relative to non-cirrhotic PBC patients. Future immunophenotyping investigations could lead to better understanding of PBC pathogenesis and progression, and also to the discovery of novel biomarkers and treatment strategies.Keywords
All Related Versions
- Published version: Scientific Reports, 10 (1), 1.
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