Molecular characterization of PANoptosis-related genes with features of immune dysregulation in systemic lupus erythematosus

Wei Sun; Pengchong Li; Min Wang; Yue Xu; Dan Shen; Xuan Zhang; Yudong Liu

doi:10.1016/j.clim.2023.109660

Molecular characterization of PANoptosis-related genes with features of immune dysregulation in systemic lupus erythematosus

Clin Immunol. 2023 Aug:253:109660. doi: 10.1016/j.clim.2023.109660. Epub 2023 Jun 7.

Authors

Wei Sun¹, Pengchong Li², Min Wang³, Yue Xu³, Dan Shen³, Xuan Zhang⁴, Yudong Liu⁵

Affiliations

¹ Department of Rheumatology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China; Department of Respiratory and Critical Care Medicine, Affiliated Jinling Hospital, Southeast University, Sch Med, Nanjing, China.
² Department of Gastroenterology, Beijing Friendship Hospital, National Clinical Research Center for Digestive Diseases, Beijing Digestive Disease center, Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases, Capital Medical University, Beijing, China.
³ Department of Rheumatology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China.
⁴ Department of Rheumatology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China. Electronic address: zxpumch2003@sina.com.
⁵ Department of Rheumatology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China; The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Beijing Hospital, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100730, PR China. Electronic address: yudongliu1983@126.com.

PMID: 37295541
DOI: 10.1016/j.clim.2023.109660

Abstract

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease. PANoptosis is a novel form of programmed cell death involved in various inflammatory diseases. This study aimed to identify the differentially-expressed PANoptosis-related genes (PRGs) involved in immune dysregulation in SLE. Five key PRGs, including ZBP1, MEFV, LCN2, IFI27, and HSP90AB1, were identified. The prediction model with these 5 key PRGs showed a good diagnostic performance in distinguishing SLE patients from controls. These key PRGs were associated with memory B cells, neutrophils and CD8 + T cells. Besides, these key PRGs were significantly enriched in pathways involving the type I interferon responses and IL-6-JAK-STAT3 signaling. The expression levels of the key PRGs were validated in peripheral blood mononuclear cells (PBMCs) of patients with SLE. Our findings suggest that PANoptosis may be implicated in the immune dysregulation in SLE by regulating the interferons and JAK-STAT signaling pathways in memory B cells, neutrophils and CD8 + T cells.

Keywords: Bioinformatics analysis; Immune cell; PANoptosis; Systemic lupus erythematosus.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

CD8-Positive T-Lymphocytes
Humans
Interferon Type I* / metabolism
Leukocytes, Mononuclear / metabolism
Lupus Erythematosus, Systemic*
Pyrin

Substances

Interferon Type I
MEFV protein, human
Pyrin