title: Pott's disease in Moroccan children: clinical features and investigation of the interleukin-12/interferon-γ pathway.
abstract: METHODS
  Tuberculosis spondylodiscitis (TS), or Pott's disease, an extra-pulmonary form of tuberculosis (TB), is rare and difficult to diagnose in children. Some cases of severe TB in children were recently explained by inborn errors of immunity affecting the interleukin-12/interferon-gamma (IL-12/IFN-γ) axis.
  
  
  OBJECTIVE
  To analyse clinical data on Moroccan children with TS, and to perform immunological and genetic explorations of the IL-12/IFN-γ axis.
  
  
  METHODS
  We studied nine children with TS diagnosed between 2012 and 2014. We investigated the IL-12/IFN-γ circuit by both whole-blood assays and sequencing of the coding regions of 14 core genes of this pathway.
  
  
  RESULTS
  A diagnosis of TS was based on a combination of clinical, biological, histological and radiological data. QuantiFERON(®)-TB Gold In-Tube results were positive in 75% of patients. Whole-blood assays showed normal IL-12 and IFN-γ production in all but one patient, who displayed impaired decreased response to IL-12. No candidate disease-causing mutations were detected in the exonic regions of the 14 genes.
  
  
  CONCLUSIONS
  TS diagnosis in children remains challenging, and is based largely on imaging. Further investigations of TS in children are required to determine the role of genetic defects in pathways that may or may not be related to the IL-12/IFN-γ axis.
authors.affiliation: Genetics Unit, Military Hospital Mohamed V, Hay Riad, Rabat, Morocco; Faculty of Science-Kenitra, Ibn Tofail University, Kenitra, Morocco.
authors.forename: S
authors.initials: S
authors.lastname: El Azbaoui
authors.affiliation: Department of Paediatric Surgery, Rabat Children Hospital, Medical and Pharmacy School of Rabat, Mohamed V University, Rabat, Morocco.
authors.forename: N
authors.initials: N
authors.lastname: Alaoui Mrani
authors.affiliation: Genetics Unit, Military Hospital Mohamed V, Hay Riad, Rabat, Morocco; Faculty of Science-Kenitra, Ibn Tofail University, Kenitra, Morocco.
authors.forename: A
authors.initials: A
authors.lastname: Sabri
authors.affiliation: Department of Paediatric Infectious Diseases, Ibn Rochd Hospital University Centre, King Hassan II University, Casablanca, Morocco.
authors.forename: Z
authors.initials: Z
authors.lastname: Jouhadi
authors.affiliation: Department of Paediatric Infectious Diseases, Ibn Rochd Hospital University Centre, King Hassan II University, Casablanca, Morocco.
authors.forename: F
authors.initials: F
authors.lastname: Ailal
authors.affiliation: Department of Paediatric Infectious Diseases, Ibn Rochd Hospital University Centre, King Hassan II University, Casablanca, Morocco.
authors.forename: A A
authors.initials: AA
authors.lastname: Bousfiha
authors.affiliation: Department of Paediatric Infectious Diseases, Ibn Rochd Hospital University Centre, King Hassan II University, Casablanca, Morocco.
authors.forename: J
authors.initials: J
authors.lastname: Najib
authors.affiliation: Department of Paediatrics, Medical and Pharmacy School of Rabat, Rabat Children Hospital, Rabat, Morocco.
authors.forename: N
authors.initials: N
authors.lastname: El Hafidi
authors.affiliation: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale Unit 1163, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Deswarte
authors.affiliation: McGill International TB Centre, The Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: E
authors.initials: E
authors.lastname: Schurr
authors.affiliation: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale Unit 1163, Paris, France; Imagine Institute, Paris Descartes University, Paris, France; Centre for the Study of Primary Immunodeficiencies, Assistance Publique-Hôpitaux de Paris, Necker Hospital for Sick Children, Paris, France.
authors.forename: J
authors.initials: J
authors.lastname: Bustamante
authors.affiliation: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale Unit 1163, Paris, France; Imagine Institute, Paris Descartes University, Paris, France; St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, USA.
authors.forename: S
authors.initials: S
authors.lastname: Boisson-Dupuis
authors.affiliation: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale Unit 1163, Paris, France; Imagine Institute, Paris Descartes University, Paris, France; St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, USA; Howard Hughes Medical Institute, New York, New York, USA; Paediatric Haematology-Immunology Unit, Necker Hospital for Sick Children, Paris, France, France.
authors.forename: J-L
authors.initials: JL
authors.lastname: Casanova
authors.affiliation: Department of Paediatrics, Medical and Pharmacy School of Rabat, Rabat Children Hospital, Rabat, Morocco; Imagine Institute, Paris Descartes University, Paris, France; St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, USA.
authors.forename: L
authors.initials: L
authors.lastname: Abel
authors.affiliation: Genetics Unit, Military Hospital Mohamed V, Hay Riad, Rabat, Morocco.
authors.forename: J
authors.initials: J
authors.lastname: El Baghdadi
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004358:Drug Therapy; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000097:blood*; D018664:Interleukin-12 / Q000097:blood*; D008279:Magnetic Resonance Imaging; D008297:Male; D009018:Morocco; D009169:Mycobacterium tuberculosis; D011446:Prospective Studies; D014057:Tomography, X-Ray Computed; D014374:Tuberculin Test; D014399:Tuberculosis, Spinal / Q000276:immunology*
chemical_list: C573415:IFNG protein, human; D018664:Interleukin-12; D007371:Interferon-gamma