The final, formatted version of the article will be published soon.
ORIGINAL RESEARCH article
Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders
Volume 15 - 2024 |
doi: 10.3389/fimmu.2024.1436114
This article is part of the Research Topic New Insights into the Pathogenesis of Idiopathic Inflammatory Myopathy View all articles
A distinct immune landscape in anti-synthetase syndrome profiled by a single-cell genomic study
Provisionally accepted
Jiayu Ding
1
Yanmei Li
2
Zhiqin Wang
1
Feng Han
2
Ming Chen
2
Jun Du
2
Tong Yang
2
Mei Zhang
2
Yingai Wang
2
Jing Xu
2
Gaoya Wang
2
Yong Xu
2
Xiuhua Wu
2
Jian Hao
2
Xinlei Liu
2
Guangxin Zhang
3
Na Zhang
2
Wenwen Sun
2
Zhigang Cai
1*
Wei Wei
2- 1 Tianjin Medical University, Tianjin, China
- 2 Tianjin Medical University General Hospital, Tianjin, China
- 3 Beijing SeekGene BioSciences Co., Ltd., Beijing, China
The objective of this study was to profile the transcriptional profiles of peripheral blood mononuclear cells (PBMCs) and their immune repertoires affected by anti-synthetase syndrome (ASS) at the single-cell level.We performed single-cell RNA sequencing (scRNA-seq) analysis of PBMCs and bulk RNA sequencing for patients with ASS (N=3) and patients with anti-melanoma differentiation-associated gene 5-positive dermatomyositis (MDA5 + DM, N=3) along with healthy controls (HCs, N=4). As ASS and MDA5 + DM have similar organ involvements, MDA5 + DM was used as a disease control. The immune repertoire was constructed by reusing the same scRNA-seq datasets. Importantly, flow cytometry was performed to verify the results from the scRNA-seq analysis.Results: After meticulous annotation of PBMCs, we noticed a significant decrease in the proportion of mucosal-associated invariant T (MAIT) cells in ASS patients compared to HCs, while there was a notable increase in the proportion of proliferative NKT cells. Compared with MDA5 + DM patients, in their PBMCs ASS patients presented substantial enrichment of interferon pathways, which were primarily mediated by IFN-II, and displayed a weak immune response. Furthermore, ASS patients exhibited more pronounced metabolic abnormalities, which may in turn affect oxidative phosphorylation pathways. Monocytes from ASS patients appear to play a crucial role as receptive signaling cells for the TNF pathway. Immunophenotyping analysis of PBMCs from ASS patients revealed an increasing trend for the clone type CQQSYSTPWTF.Using single-cell genomic datasets of ASS PBMCs, we revealed a distinctive profile in the immune system of individuals with ASS, compared to that with MDA5 + DM or healthy controls.
Keywords: Clinical science, Auto-immune diseases, single-cell genomics, Anti-synthetase syndrome, MDA5 + Dermatomyositis anti-synthetase syndrome (ASS), Single-cell RNA sequencing (scRNAseq), mucosal-associated invariant T (MAIT) cell, IFN-II
Received: 21 May 2024; Accepted: 30 Sep 2024.
Copyright: © 2024 Ding, Li, Wang, Han, Chen, Du, Yang, Zhang, Wang, Xu, Wang, Xu, Wu, Hao, Liu, Zhang, Zhang, Sun, Cai and Wei. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Zhigang Cai, Tianjin Medical University, Tianjin, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.