Transcriptomic Features of systemic lupus erythematosus Patients in Flare and Changes during Acute In-Hospital Treatment.

Dec 25, 2023

Experts: Zhongyi Liu,Li Shao,Fei Hou,Weiyang Li,Yong-Fei Wang,Hong Feng,Frank Qingyun Wang,Yao Lei,Lichuan Zheng,Rui Liang,Jian Li,Xianghua Guo,Lili Zhang,Yanfang Zhang,Jing Yang,Xiao Qin,Wei Wei,Xingtian Yang,Xiao Dang,Wen Ma,Chun Hing She,Qingsheng Kong,Jing Yang,Bo Ban,Yu Lung Lau,Qin Song,Wanling Yang

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with varying symptoms and multi-organ damage. Relapse-remission cycles often persist for many patients for years with the current treatment. Improved understanding of molecular changes caused by SLE flare and intensive treatment may result in more targeted therapies.
RNA-sequencing was performed on peripheral blood mononuclear cells (PBMCs) from 65 SLE patients in flare, collected both before (SLE1) and after (SLE2) in-hospital treatment, along with 15 healthy controls (HC). Differentially expressed genes (DEGs) were identified among the three groups. Enriched functions and key molecular signatures of the DEGs were analyzed and scored to elucidate the transcriptomic changes during treatment.
Few upregulated genes in SLE1 vs HC were affected by treatment (SLE2 vs SLE1), mostly functional in interferon signalling (IFN), plasmablasts, and neutrophils. IFN and plasmablast signatures were repressed, but the neutrophil signature remained unchanged or enhanced by treatment. The IFN and neutrophil scores together stratified the SLE samples. IFN scores correlated well with leukopenia, while neutrophil scores reflected relative cell compositions but not cell counts.
In-hospital treatment significantly relieved SLE symptoms with expression changes of a small subset of genes. Notably, IFN signature changes matched SLE flare and improvement, while enhanced neutrophil signature upon treatment suggested the involvement of low-density granulocytes (LDG) in disease development.

© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

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ABOUT THE EXPERTS

Zhongyi Liu,Li Shao,Fei Hou,Weiyang Li,Yong-Fei Wang,Hong Feng,Frank Qingyun Wang,Yao Lei,Lichuan Zheng,Rui Liang,Jian Li,Xianghua Guo,Lili Zhang,Yanfang Zhang,Jing Yang,Xiao Qin,Wei Wei,Xingtian Yang,Xiao Dang,Wen Ma,Chun Hing She,Qingsheng Kong,Jing Yang,Bo Ban,Yu Lung Lau,Qin Song,Wanling Yang

Zhongyi Liu

Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong kong, China.

Li Shao

Department of Rheumatology and Lupus Research Institute, Affiliated Hospital of Jining Medical University, Jining, Shandong, China.

Fei Hou

Medical Laboratory of Jining Medical University, Jining Medical University, Jining, Shandong, China.

Weiyang Li

School of Biological Science, Jining Medical University, Rizhao, Shandong, China.

Yong-Fei Wang

School of Life and Health Sciences, School of Medicine, and Warshel Institute for Computational Biology, The Chinese University of Hong Kong-, Shenzhen, Shenzhen, Guangdong, China.

Hong Feng

Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong kong, China.

Frank Qingyun Wang

Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong kong, China.

Yao Lei

Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong kong, China.

Lichuan Zheng

Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong kong, China.

Rui Liang

Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong kong, China.

Jian Li

Department of Rheumatology and Lupus Research Institute, Affiliated Hospital of Jining Medical University, Jining, Shandong, China.

Xianghua Guo

Department of Rheumatology and Lupus Research Institute, Affiliated Hospital of Jining Medical University, Jining, Shandong, China.

Lili Zhang

Department of Rheumatology and Lupus Research Institute, Affiliated Hospital of Jining Medical University, Jining, Shandong, China.

Yanfang Zhang

Department of Rheumatology and Lupus Research Institute, Affiliated Hospital of Jining Medical University, Jining, Shandong, China.

Jing Yang

Department of Rheumatology and Lupus Research Institute, Affiliated Hospital of Jining Medical University, Jining, Shandong, China.

Xiao Qin

Collaborative Innovation Center for Birth Defect Research and Transformation of Shandong Province, Jining Medical University, Jining, Shandong, China.

Wei Wei

Medical Research Center, Affiliated Hospital of Jining Medical University, Jining, Shandong, China.

Xingtian Yang

Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong kong, China.

Xiao Dang

Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong kong, China.

Wen Ma

Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong kong, China.

Chun Hing She

Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong kong, China.

Qingsheng Kong

Collaborative Innovation Center for Birth Defect Research and Transformation of Shandong Province, Jining Medical University, Jining, Shandong, China.

Jing Yang

Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong kong, China.

Bo Ban

Department of Endocrinology, Affiliated Hospital of Jining Medical University, Jining, Shandong, China.

Chinese Research Center for Behavior Medicine in Growth and Development, Shandong, China.

Yu Lung Lau

Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong kong, China.

Qin Song

Department of Rheumatology and Lupus Research Institute, Affiliated Hospital of Jining Medical University, Jining, Shandong, China.

Wanling Yang

Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong kong, China.