title: IL-4 specific-response in whole blood associates with human Cystic Echinococcosis and cyst activity.
abstract: OBJECTIVE
  Human Cystic Echinococcosis (CE) is estimated in 2-3 million global cases. CE diagnosis and clinical management are based on imaging and serology, which lacks sensitivity and does not provide cyst stage information. This study aimed to evaluate tools for improving diagnosis by analysing the Interleukin (IL)-4-response to Antigen B (AgB) of Echinococcus granulosus.
  
  
  METHODS
  Whole blood (WB) and peripheral blood mononuclear cells were stimulated with AgB. IL-4 levels were measured by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  WB 1-day stimulation resulted the best experimental condition for evaluating AgB IL-4-response. IL-4 levels were significantly higher in CE patients than healthy donors (p ≤ 0.0001). A ROC analysis showed significant area under the curve (AUC) results (AUC, 0.85; p = 0.0001) identifying an IL-4 level cut-off point ≥0.39 pg/mL which predicted CE with 71.4% sensitivity and 93.3% specificity. Moreover, we found that IL-4 levels were significantly increased in patients with active cysts compared to those with inactive cysts (p ≤ 0.0001). ROC analysis showed significant AUC results (0.94; p = 0.0001) with a cut-off point of 4.6 pg/mL which predicted active cysts with 84.6% sensitivity and 92% specificity.
  
  
  CONCLUSIONS
  We found immunological correlates associated with CE and biological cyst activity.
authors.affiliation: Translational Research Unit, Department of Epidemiology and Preclinical Research, "L. Spallanzani" National Institute for Infectious Diseases (INMI), Rome, Italy.
authors.forename: Linda
authors.initials: L
authors.lastname: Petrone
authors.affiliation: Translational Research Unit, Department of Epidemiology and Preclinical Research, "L. Spallanzani" National Institute for Infectious Diseases (INMI), Rome, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Vanini
authors.affiliation: Translational Research Unit, Department of Epidemiology and Preclinical Research, "L. Spallanzani" National Institute for Infectious Diseases (INMI), Rome, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Petruccioli
authors.affiliation: Unit of Surgery and Transplantation, "Interaziendale" Department P.O.I.T., Polo Ospedaliero Interaziendale San Camillo-INMI Lazzaro Spallanzani, Rome, Italy.
authors.forename: Giuseppe Maria
authors.initials: GM
authors.lastname: Ettorre
authors.affiliation: Department of Radiology, "L. Spallanzani" National Institute for Infectious Diseases (INMI), Rome, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Busi Rizzi
authors.affiliation: Department of Radiology, "L. Spallanzani" National Institute for Infectious Diseases (INMI), Rome, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Schininà
authors.affiliation: Department of Epidemiology and Preclinical Research, National Institute for Infectious Diseases (INMI), Rome, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Girardi
authors.affiliation: Department of Infectious, Parasitic and Immunomediated Diseases, Istituto Superiore di Sanità (ISS), Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ludovisi
authors.affiliation: Department of Infectious, Parasitic and Immunomediated Diseases, Istituto Superiore di Sanità (ISS), Rome, Italy.
authors.forename: María Ángeles
authors.initials: MÁ
authors.lastname: Gómez-Morales
authors.affiliation: Department of Infectious, Parasitic and Immunomediated Diseases, Istituto Superiore di Sanità (ISS), Rome, Italy.
authors.forename: Edoardo
authors.initials: E
authors.lastname: Pozio
authors.affiliation: Department of Infectious and Tropical Diseases, Sant'Andrea Hospital University of Rome"Sapienza", Rome, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Teggi
authors.affiliation: Translational Research Unit, Department of Epidemiology and Preclinical Research, "L. Spallanzani" National Institute for Infectious Diseases (INMI), Rome, Italy. Electronic address: delia.goletti@inmi.it.
authors.forename: Delia
authors.initials: D
authors.lastname: Goletti
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology; D004443:Echinococcosis / Q000175:diagnosis / Q000276:immunology* / Q000469:parasitology*; D048209:Echinococcus granulosus / Q000276:immunology* / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D015847:Interleukin-4 / Q000097:blood* / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008074:Lipoproteins / Q000276:immunology* / Q000302:isolation & purification; D008297:Male; D008875:Middle Aged; D012680:Sensitivity and Specificity
chemical_list: D000947:Antigens, Helminth; D008074:Lipoproteins; C514022:antigen B, Echinococcus granulosus; D015847:Interleukin-4
keywords: Active versus inactive cyst; Antigen B; Cysts monitoring; Diagnosis; Human Cystic Echinococcosis; IL-4; Serology; Ultrasonography; Whole blood