title: Serum concentrations of A Proliferation-Inducing Ligand (APRIL) are elevated in sepsis and predict mortality in critically ill patients.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany.
authors: Christoph
authors: C
authors: Roderburg
authors: Alexander
authors: A
authors: Koch
authors: Frank
authors: F
authors: Tacke
authors: Lukas
authors: L
authors: Nieuwenhuijsen
authors: Jan
authors: J
authors: Bruensing
authors: David
authors: D
authors: Vargas Cardenas
authors: Karina
authors: K
authors: Kreggenwinkel
authors: Mihael
authors: M
authors: Vucur
authors: Christiane
authors: C
authors: Koppe
authors: Philipp
authors: P
authors: Jungebluth
authors: Claudia
authors: C
authors: Seikrit
authors: Mark
authors: M
authors: Luedde
authors: Christian
authors: C
authors: Trautwein
authors: Tom
authors: T
authors: Luedde
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D016638:Critical Illness; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D018805:Sepsis / Q000097:blood* / Q000401:mortality*; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000097:blood*
chemical_list: D015415:Biomarkers; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13
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