Impaired Circulating Antibody-Secreting Cells Generation Predicts the Dismal Outcome in the Elderly Septic Shock Patients

Abstract

Purpose Sepsis is a condition that derives from a dysregulated host response to infection. Although B lymphocytes play a pivotal role in immune response, little is known about status of their terminally differentiated cells, antibody-secreting cells (ASCs) during immunosuppressive phase of sepsis, especially in elderly patients. Our aim was to extensively characterize the immune functions of ASCs in elderly septic patients. Patients and Methods Clinical and laboratory data were collected on days 1, 3, and 7 of hospitalization. Circulating ASCs were evaluated by flow cytometry from fresh whole blood in elderly septic patients at the onset of disease. RNA sequencing analyzed ASCs gene expression profile. Receiver operating characteristic (ROC) curve analysis and logistic regression predicted the survival rate of 28-day mortality. Results A total of 103 septic patients were enrolled. The number and proportion of ASCs among total lymphocytes dramatically increased in septic patients, and RNA sequencing analysis showed that ASCs from septic patients exhibited a different gene expression profile. Furthermore, we found these ASCs could promote the function of T cells. Logistic regression analysis showed ASCs population was an independent outcome predictor in septic shock patients. Conclusion Our study revealed the complex nature of immune disorders in sepsis and identified circulating ASCs population as a useful biomarker for predicting mortality in elderly septic patients, which provided a novel clue to combat this severe disease.

The Changes in the Quantity of Lymphocyte Subpopulations during the Process of Sepsis

“…Animal experiments have shown that IRA-B cells exert a protective effect in sepsis mediated through the growth factor granulocyte-macrophage colony-stimulating factor (GM-CSF) [65]. In the human body, GM-CSF participates in innate immunity against infections through various pathways [66], including promoting phagocytosis by neutrophils, regulating the defensive factor IgM, and promoting the survival of IRA-B cells through autoregulation. Unfortunately, experiments delivering GM-CSF to the peripheral circulation to improve the prognosis of sepsis patients have not achieved the expected results.…”

“…ASCs (antibody-secreting cells) are the foundation of humoral immunity [67]. Xu, Huihui, and colleagues [66] found a significant increase in ASCs in sepsis patients compared to healthy controls in clinical experiments. At the same time, they detected the increased proliferation of CD4+ T cells and the secretion of pro-inflammatory cytokines IFN-γ and IL-17 in In the collected clinical studies, there is a lack of meaningful results regarding B lymphocyte counts.…”