Serum concentrations of A Proliferation-Inducing Ligand (APRIL) are elevated in sepsis and predict mortality in critically ill patients

Abstract

Introduction: Inflammatory and autoimmune diseases have been associated with the tumor necrosis factor superfamily member "A PRoliferation Inducing Ligand" (APRIL). However, up to now, APRIL has not been investigated in critical illness or sepsis. We therefore analyzed APRIL serum concentrations in a large cohort of well-characterized intensive care unit patients.

Methods: Serum concentrations of APRIL were measured in 246 critically ill patients, of which 157 fulfilled sepsis criteria in comparison with 81 healthy controls. Clinical data were recorded and correlated with APRIL serum levels.

Results: We detected strongly elevated serum levels of APRIL in critically ill patients compared with healthy controls. Levels of APRIL were further elevated in sepsis and significantly correlated with classical markers of inflammation, bacterial infection, or multiorgan failure. Consequently, high APRIL levels were associated with an unfavorable prognosis and predicted mortality with higher diagnostic accuracy than established prognostic scoring systems such as the Acute Physiology and Chronic Health Evaluation II score.

Conclusion: Serum levels of APRIL were significantly elevated in intensive care unit patients, with the highest concentrations in septic patients, and associated with unfavorable outcome. Besides being used as a single marker, APRIL may be implemented into established scoring systems to further improve their sensitivity and specificity in predicting patient's prognosis.

Keywords: ANCA; APACHE; APC; APRIL; AUC; Acute Physiology and Chronic Health Evaluation; B-cell maturation antigen; BCMA; BMI; C-reactive protein; CRP; CVID; Critical illness; ELISA; FACS; GFR; ICU; IL-6; INR; Ig; PCHE; PCT; ROC; SAPS; SOFA; Sepsis; Sequential Organ Failure Assessment; Simplified Acute Physiology Score; Survival; TACI; TNF; TNFR; a proliferation-inducing ligand; antigen-presenting cell; antineutrophil cytoplasmic autoantibody; area under the curve; body mass index; common variable immunodeficiency; enzyme-linked immunosorbent assay; fluorescence-activated cell sorting; glomerular filtration rate; immunoglobulin; intensive care unit; interleukin-6; international normalized ratio; mRNA; messenger RNA; procalcitonin; pseudocholinesterase; receiver operating characteristic; transmembrane activator and CAML interactor; tumor necrosis factor; tumor necrosis factor receptor.