The role of TNF-α superfamily members in immunopathogenesis of sepsis

Background: Members of TNF alpha superfamily, A proliferation inducing ligand (APRIL), B-cell activating factor (BAFF) and Transmembrane activator and calcium cyclophylin interactor (TACI) are main regulators of B-cell function. The aim of this study was to evaluate concentrations of APRIL, BAFF and soluble TACI (sTACI) receptor in septic patients compared to healthy controls and compare concentrations of these biomarkers depending on sepsis severity and outcome. Materials and methods: A total of 115 septic patients and 30 healthy volunteers were included and concentrations of APRIL, BAFF and sTACI were determined in all subjects at the admission (ELISA R&D Systems tests). Concentrations of these biomarkers in function of sepsis severity (sepsis n = 94 and septic shock n = 21) and outcome (lethal n = 40, recovery n = 75) were tested, as well as correlations with APACHE II and SOFA scores, immunoglobulins, complement, PCT and CRP concentrations. Results: Concentrations of all three biomarkers were significantly increased in septic patients compared to controls (AUC(APRIL) = 0.982, AUC(BAFF) = 0.873, AUC(sTACI) = 0.683). Higher concentrations of APRIL and sTACI (p = 0.033, p = 0.037), and lower concentrations of BAFF (p = 0.005) were observed in patients with septic shock compared to sepsis. BAFF concentrations correlated positively with IgM, C3 and C4 levels. sTACI and APRIL were shown to be predictors of lethal outcome (p = 0.003, p = 0.049). Conclusions: Concentrations of observed TNFa superfamily members are significantly increased in septic patients, confirming their role in sepsis pathogenesis. Higher concentrations of anti-inflammatory sTACI receptor correlated with severity of sepsis and poorer prognosis, thus potentially indicating domination of anti-inflammatory response in septic patients with worse outcome.