Single-Cell Transcriptome Analysis Reveals The Differences Of Peripheral Immune Cells Between Systemic Lupus Erythematosus And Sepsis Patients

Research BackgroundSystemic lupus erythematosus(SLE)is a serious autoimmune disease that can affect various organs and systems in the body.Due to the weakened immune system of SLE patients,they are more susceptible to bacterial,fungal,and viral infections.Additionally,drugs commonly used to treat this disease,such as steroids and immunosuppressants,may also suppress the patient’s immune system,further increasing the risk of infection.Research has shown that infection is one of the leading causes of death in SLE patients.When the body’s response to infection becomes dysregulated,it can lead to sepsis.Sepsis is a life-threatening systemic inflammatory response that has become a major cause of infection-related deaths worldwide.It can lead to multiple organ dysfunction syndrome(MODS),which severely threatens the patient’s life.Although systemic lupus erythematosus and sepsis have different pathogenesis and treatment methods,they do have some similar clinical manifestations.For example,due to immune system disorders,patients with systemic lupus erythematosus may experience clinical symptoms similar to sepsis,such as difficulty breathing,high fever,and abnormal blood pressure.These similar manifestations may confuse doctors when judging the condition,thus missing the optimal treatment time.Therefore,a deep understanding of the molecular differences between these two diseases is crucial.By better understanding the patient’s disease status and selecting appropriate intervention methods,the success rate of treatment and prognosis can be effectively improvedObjectivesThis study aims to explore the changes in gene expression of different immune cell types in SLE and sepsis patients through single-cell transcriptomics,in order to find new potential biomarkers for the early diagnosis of these diseases and deepen our understanding of their pathogenesis.MethodsIn this study,peripheral blood whole-blood samples were collected from SLE and sepsis patients.Peripheral blood mononuclear cells were separated by density gradient centrifugation,and cells were identified through viability and density screening.High-quality cells were then selected for single-cell transcriptomic library construction and sequencing.The obtained gene expression matrix was integrated with data from healthy donors in public databases,and bioinformatics tools were used to analyze the similarities and differences in gene expression between the two diseases and predict functional differences.Results1.Three sepsis patients and three SLE patients were included based on inclusion criteria.2.After quality control and filtering,a total of39,058 high-quality cells were obtained for subsequent analysis.3.Through clustering,29 different cell subgroups were identified,including two types ofγδT cells.4.The expression patterns of reported SLE-related gene families in the two types of γδT cells were consistent with the gene expression trend of αβT cells reported in the literature,Among them,STAT1 gene is found in two categories γδ Significant differences in T cells.5.Two types of patients with sepsis and systemic lupus erythematosus γδ The enrichment analysis of differential gene pathways between T cells showed that multiple immune system pathways,including Toll like receptor signaling pathway and IL-17 signaling pathway,were significantly enriched in patients with systemic lupus erythematosus.6.Cell communication analysis of γδ T cells suggested that they may activate downstream pathways and participate in immune responses through interaction with CD4+T cells.ConclusionsCompared with sepsis patients,γδT cells in SLE patients may trigger a cascade reaction by interacting with CD4+T cells,significantly positively enriching immune-related pathways to respond to inflammatory reactions.