Downregulation of JKAP is correlated with elevated disease risk, advanced disease severity, higher inflammation, and poor survival in sepsis

Abstract

ObjectiveThis study aimed to explore the association of JKAP with sepsis risk and investigate its correlation with disease severity, inflammatory cytokines, and survival in sepsis patients.MethodsA hundred and one sepsis patients along with 100 healthy controls were enrolled, and their blood serum samples were collected for JKAP and inflammatory cytokines measurement by enzyme‐linked immunoassay. The difference in serum JKAP between sepsis patients and healthy controls was determined. Among sepsis patients, the correlation of JKAP with disease severity, laboratory indexes, inflammatory cytokines, 28‐day mortality, and accumulating survival was analyzed.ResultsJNK pathway–associated phosphatase level was decreased in sepsis patients compared with healthy controls and presented with good value in predicting decreased sepsis risk (AUC = 0.896 [95% CI: 0.851‐0.941]). And its low expression was associated with advanced disease severity (APACHE II score and SOFA score) and systemic inflammation (CRP, PCT, TNF‐α, IL‐1β, IL‐6, and IL‐17) in sepsis patients. Additionally, JKAP level was decreased in deaths compared with survivors and had good value in distinguishing deaths from survivors (AUC = 0.742 [95% CI: 0.636‐0.849]). Further, Kaplan‐Meier curve analysis disclosed that JKAP high expression predicted more prolonged accumulating survival in sepsis patients.ConclusionJNK pathway–associated phosphatase is of good value in predicting lower sepsis risk, and its downregulation correlates with advanced disease severity, higher level of systemic inflammation, and poor survival in sepsis patients.

The correlation of JKAP with risk, severity, inflammation and in-hospital mortality of severe acute pancreatitis

“…Considering that SAP is an extremely severe immune and inflammatory disease, we hypothesized that JKAP might be dysregulated and play an important role in the pathogenesis of SAP. Our study displayed that JKAP could well distinguish SAP patients from healthy controls (AUC: 0.914, 95%CI: Previous studies have elucidated that downregulation of JKAP is associated with poor prognosis in IBD and sepsis [9,11]. For example, low JKAP level predicts active status of Crohn's disease and ulcerative colitis [9].…”

“…For instance, JKAP expression in peripheral blood T cells is lower in SLE patients than that in health volunteers, and the downregulation of JKAP expression in T cells is associated with higher daily urinary protein amounts and poor renal outcomes in SLE patients [10]. Another study illuminates that the serum JKAP is downregulated in sepsis patients compared with healthy volunteers, and the downregulation of JKAP is correlated with advanced disease severity (APACHE II score and SOFA score) and systemic inflammation (CRP, PCT, TNF-α, IL-1β, IL-6 and IL-17) in sepsis patients [11].…”

“…Previous studies have revealed that the downregulation of JKAP is involved in the development and progression of several autoimmune and inflammatory diseases such as SLE and sepsis [10,11]. For instance, JKAP expression in peripheral blood T cells is lower in SLE patients than that in health volunteers, and the downregulation of JKAP expression in T cells is associated with higher daily urinary protein amounts and poor renal outcomes in SLE patients [10].…”

“…For example, low JKAP level predicts active status of Crohn's disease and ulcerative colitis [9]. Another study reports that JKAP presents a good value in differentiating deaths from survivors in sepsis patients [11]. However, no study reports the association of JKAP level with prognosis in SAP patients.…”

“…JKAP is abundantly expressed in various types of mammalian cells such as T cells, B cells and natural killer cells, which participates in important biological processes such as inflammatory and immune responses in human autoimmune and inflammatory disorders [9]. A few studies have displayed that the downregulation of JKAP is negatively correlated with disease severity and inflammation in inflammatory bowel disease (IBD), systemic lupus erythematosus (SLE) and sepsis [9][10][11]. Based on the role of JKAP in the regulation of inflammation and immune response and its association with the etiology of several inflammatory disorders, we hypothesized that JKAP might be involved in the development and progression of SAP as well.…”