Single-cell Sequencing Based Analysis Of The B Cell Senescence Heterogeneity In Peripheral Blood Of Systemic Lupus Erythematosus

BackgroundSystemic lupus erythematosus(SLE)is a common chronic autoimmune disease,which can involve all organs and tissues of the whole body.Antibody serological indicators are often used to judge the diagnosis and treatment effect of SLE.B cells are important antibody producers of SLE and are closely related to the pathogenesis.Aging is a concept emerging in recent years.It is a gradual loss of physiological integrity,which can lead to impaired function and increased risk of death.Aging can also occur in autoimmune diseases.However,there are few studies on aging and autoimmune diseases,especially SLE.The development of single-cell sequencing technology makes it possible to comprehensively describe cellular and functional heterogeneity as well as the dynamic changes of immune system during aging.It can accurately judge whether the changes of immune aging occur in cells from the four characteristics of aging:chronic inflammation,epigenetic changes,cell aging,and cell communication,and explain how the changes take place.MethodsWith informed consent,the PBMC samples of 6 patients with SLE,6 patients with rheumatoid arthritis(RA)and 3 healthy controls(HC)were sequenced by single cell transcriptome,and combined with the SLE data of 5 patients from public databases as an assistant comparison verification,to explore the immune senescence of SLE B cells.Firstly,cells were divided into immune cell groups by cell reduction clustering,and then B cells were further subdivided.The core genes affecting SLE B cells were found by differential analysis and public data,and then the differential genes of SLE and RA were functional analyzed by enrichment analysis.Pseudo-time series analysis determined the differentiation characteristics of SLE B cells,cell communication analysis examined the changes in the major secretion pathways of SLE and RA B cells,and finally predicted the basic regulatory transcription factors of SLE B cells by transcription factor analysis.ResultsIn this study,PBMC cell maps of SLE and RA by single-cell sequencing were successfully mapped,revealing disease-specific cell subgroups.Through single-cell transcriptome sequencing analysis,it was found that B-cells in SLE patients in this study showed decreased function and decreased vitality.B cell senescence in SLE is characterized by increased type I IFN intensity,enhanced viral immune response,enhanced endoplasmic reticulum processing pathways,decreased cell adhesion regulation,monocyte differentiation,and decreased B cell activation.Meanwhile,the regulatory ability of SLE secretion pathways such as CD70,APRIL,BAG,IL16,VISFATIN and BTLA pathways is weakened.We identified three genes,ISG15,IFI44L,IFITM1,and the core transcription factor STAT1,which are closely related to SLE plasma cell differentiation and immune aging,opening up ideas for the study on the pathogenesis of B-cell involvement in SLE and other autoimmune diseases,and providing new clues for the search for future therapeutic targets such as JAK inhibitors for SLE.