title: Detection of interleukin-2 is not useful for distinguishing between latent and active tuberculosis in clinical practice: a prospective cohort study.
abstract: OBJECTIVE
  Previous reports have identified interleukin-2 (IL-2), quantified in the supernatants of QuantiFERON®-TB Gold In-tube (QFT) after 72 h of incubation, as a potential biomarker for distinguishing between latent and active tuberculosis (TB). However, its validity has not been tested in an appropriate clinical cohort.
  
  
  METHODS
  A multicentre study of 161 consecutive adult patients undergoing evaluation for active TB at eight TB Units in Spain. Interferon-γ (IFN-γ) and IL-2 were assessed in the supernatant of QFT after 16-24 h and 72 h of incubation. The accuracy of IL-2 for indicating latent TB infection (LTBI) was assessed by receiving operating characteristic curves. .
  
  
  RESULTS
  Twenty-eight participants were not infected, 43 had LTBI, 69 had TB, and 21 were not classifiable. Median (interquartile range) IL-2 concentrations after 72 h of incubation were 0.0 pg/mL (0.0-0.0) in uninfected individuals, 261.0 pg/mL (81.0-853.0) in LTBI individuals, 166.5 pg/mL (33.5-551.5) in patients with extrapulmonary TB, 95.0 pg/mL (26.0-283.0) in patients with smear-negative pulmonary TB, and 38.5 pg/mL (7.5-178.0) in patients with smear-positive pulmonary TB (p <0.0001). The area under the curve of the receiving operating characteristic curve (95% CI) of IL-2 after 72 h of incubation for the diagnosis of LTBI was 0.63 (0.53-0.74) when all TB cases were considered as a single group, ranging from 0.59 (0.47-0.71) to 0.72 (0.58-0.85) when only extrapulmonary and smear-positive pulmonary TB cases respectively were considered.
  
  
  CONCLUSIONS
  Quantification of IL-2 in the supernatant of QFT after a prolonged incubation is not useful to distinguish between LTBI and active disease in clinical practice.
authors.affiliation: Service of Infectious Diseases, Bellvitge University Hospital-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain; Department of Clinical Sciences, University of Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain. Electronic address: msantin@bellvitgehospital.cat.
authors.forename: M
authors.initials: M
authors.lastname: Santin
authors.affiliation: Service of Immunology, Bellvitge University Hospital-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Morandeira-Rego
authors.affiliation: Service of Microbiology, Bellvitge University Hospital-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain; Department of Pathology and Experimental Therapy, University of Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Alcaide
authors.affiliation: Unit of Infectious Diseases, Hospital Universitario Lucus Augusti, Lugo, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Rabuñal
authors.affiliation: Unit of Tuberculosis, Service of Infectious Diseases-Internal Medicine, Complexo Hospitalario Universitario de Pontevedra, Pontevedra, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Anibarro
authors.affiliation: Service of Respiratory Diseases, Hospital Universitario Marqués de Valdecilla, Santander, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Agüero-Balbín
authors.affiliation: Respiratory Diseases, Hospital General Parc Sanitari Sant Joan de Déu, Sant Boi de Llobregat, Barcelona.
authors.forename: X
authors.initials: X
authors.lastname: Casas-Garcia
authors.affiliation: Unidad de Gestión Clínica Enfermedades Infecciosas y Microbiología, Hospital de Jerez, Jerez de la Frontera, Cádiz, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Pérez-Escolano
authors.affiliation: Clinic Unit of Infectious Diseases and Preventive Medicine, Hospital Virgen Macarena, Sevilla, Spain.
authors.forename: M D
authors.initials: MD
authors.lastname: Navarro
authors.affiliation: Service of Infectious Diseases, Institut Mar d'Investigacions Mèdiques (IMIM), Hospital del Mar, Barcelona, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Sánchez
authors.affiliation: Service of Microbiology, Hospital Universitario Lucus Augusti, Lugo, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Coira-Nieto
authors.affiliation: Service of Microbiology, Complexo Hospitalario Universitario de Pontevedra, Pontevedra, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Trigo-Daporta
authors.affiliation: Service of Respiratory Diseases, Hospital Universitario Marqués de Valdecilla, Santander, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Martinez-Meñaca
authors.affiliation: Service of Microbiology, Hospital General Parc Sanitari Sant Joan de Déu, Sant Boi de Llobregat, Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Gonzalez-Cuevas
authors.affiliation: Unidad de Gestión Clínica Enfermedades Infecciosas y Microbiología, Hospital de Jerez, Jerez de la Frontera, Cádiz, Spain.
authors.forename: M D
authors.initials: MD
authors.lastname: López-Prieto
authors.affiliation: Clinic Unit of Infectious Diseases and Preventive Medicine, Hospital Virgen Macarena, Sevilla, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Domínguez-Castellano
authors.affiliation: Service of Infectious Diseases, Institut Mar d'Investigacions Mèdiques (IMIM), Hospital del Mar, Barcelona, Spain.
authors.forename: N
authors.initials: N
authors.lastname: Jové
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D007376:Interleukin-2 / Q000097:blood*; D055985:Latent Tuberculosis / Q000097:blood / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013030:Spain; D014376:Tuberculosis / Q000097:blood / Q000175:diagnosis*; D014397:Tuberculosis, Pulmonary / Q000097:blood / Q000175:diagnosis*
chemical_list: D015415:Biomarkers; C573415:IFNG protein, human; C508594:IL2 protein, human; D007376:Interleukin-2; D007371:Interferon-gamma
keywords: Active tuberculosis; Interferon-γ; Interleukin-2; Latent tuberculosis infection; QuantiFERON