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Low Penetrance, Broad Resistance, and Favorable Outcome of Interleukin 12 Receptor β1 Deficiency

  • Fieschi, Claire Laboratory of Human Genetics of Infectious Diseases, University René Descartes INSERM U550, Necker Medical School
  • Dupuis, Stéphanie Laboratory of Human Genetics of Infectious Diseases, University René Descartes INSERM U550, Necker Medical School
  • Catherinot, Emilie Laboratory of Human Genetics of Infectious Diseases, University René Descartes INSERM U550, Necker Medical School
  • Feinberg, Jacqueline Laboratory of Human Genetics of Infectious Diseases, University René Descartes INSERM U550, Necker Medical School
  • Bustamante, Jacinta Laboratory of Human Genetics of Infectious Diseases, University René Descartes INSERM U550, Necker Medical School
  • Breiman, Adrien Laboratory of Human Genetics of Infectious Diseases, University René Descartes INSERM U550, Necker Medical School
  • Altare, Frédéric Laboratory of Human Genetics of Infectious Diseases, University René Descartes INSERM U550, Necker Medical School
  • Baretto, Richard MRC Center for Immune Regulation, The Medical School, University of Birmingham, Birmingham B15 2TT, United Kingdom
  • Le Deist, Françoise INSERM U429, Necker Hospital
  • Kayal, Samer INSERM U411, Necker Hospital
  • Koch, Hartmut Department of Pediatrics, St. Marienhospital, D-49377 Vechta, Germany
  • Richter, Darko Division of Allergy and Clinical Immunology, Department of Pediatrics, University Hospital Center, 10000 Zagreb, Croatia
  • Brezina, Martin Pediatric Pneumology and Phtiseology Clinic SPAM, National Institute of Tuberculosis and Respiratory Diseases, 82556 Bratislava, Slovak Republic
  • Aksu, Guzide Division of Pediatric Immunology, Department of Pediatrics, The Medical School, Ege University, 35100 Izmir, Turkey
  • Wood, Phil Department of Clinical Chemistry and Immunology, Leeds General Infirmary, Leeds LS1 3EX, United Kingdom
  • Al-Jumaah, Suliman Department of Pediatrics, King Faycal Hospital and Research Center, 11211 Riyadh, Saudi Arabia
  • Raspall, Miquel Pediatric Infectious Diseases Unit and Department of Immunology, Vall d'Hebron Hospital, 08035 Barcelona, Spain
  • da Silva Duarte, Alberto José Primary Immunodeficiency Unit, Department of Dermatology of the Clinical Hospital, and Laboratory of Clinical and Experimental Allergy and Immunology, University of Sao Paulo Medical School, 01246-903 Sao Paulo, Brazil
  • Tuerlinckx, David Departement of Pediatrics, Catholic University of Louvain at Mont-Godinne, 5530 Yvoir, Belgium
  • Virelizier, Jean-Louis Department of Molecular Medicine, Institut Pasteur, 75015 Paris, France
  • Fischer, Alain Pediatric Immunology and Hematology Unit, Necker Hospital
  • Enright, Andrea Department of Pediatrics, Stanford University Medical Center, Stanford, CA 94010
  • Bernhöft, Jutta Department of Pediatric Hematology and Oncology, D35385 Giessen, Germany
  • Cleary, Aileen M. Department of Pediatrics, Stanford University Medical Center, Stanford, CA 94010
  • Vermylen, Christiane Department of Pediatric Hematology, Cliniques Universitaires Saint Luc, Louvain Medical School, B-1200 Brussels, Belgium
  • Rodriguez-Gallego, Carlos Department of Immunology, Gran Canaria Dr Negrin Hospital, 35020 Las Palmas, Spain
  • Davies, Graham Division of Paediatric Infectious Diseases, Great Ormond Street Children's Hospital, London WC1N 3JH, United Kingdom
  • Blütters-Sawatzki, Renate Department of Pediatric Hematology and Oncology, D35385 Giessen, Germany
  • Siegrist, Claire-Anne Department of Pediatrics, University Hospital of Geneva, 1211, Geneva 4, Switzerland
  • Ehlayel, Mohammad S. Hamad Medical Corporation, P.O. Box: 3050, Doha, Qatar
  • Novelli, Vas Division of Paediatric Infectious Diseases, Great Ormond Street Children's Hospital, London WC1N 3JH, United Kingdom
  • Haas, Walther H. Center for Epidemiology of Infectious Diseases, Robert Koch Institute, D-10963 Berlin, Germany
  • Levy, Jacob Division of Pediatrics, Soroka Medical Center and Faculty of Health Sciences, Ben Gurion University, Beer Sheva 84101, Israel
  • Freihorst, Joachim Pediatric Pulmonology and Neonatology, Hannover Medical School, D-30623 Hannover, Germany
  • Al-Hajjar, Sami Department of Pediatrics, King Faycal Hospital and Research Center, 11211 Riyadh, Saudi Arabia
  • Nadal, David Division of Infectious Diseases, University Children's Hospital of Zürich, CH-8032 Zürich, Switzerland
  • de Moraes Vasconcelos, Dewton Primary Immunodeficiency Unit, Department of Dermatology of the Clinical Hospital, and Laboratory of Clinical and Experimental Allergy and Immunology, University of Sao Paulo Medical School, 01246-903 Sao Paulo, Brazil
  • Jeppsson, Olle Children's Hospital, Huddinge University Hospital, 141 86 Huddinge, Sweden
  • Kutukculer, Necil Division of Pediatric Immunology, Department of Pediatrics, The Medical School, Ege University, 35100 Izmir, Turkey
  • Frecerova, Klara Pediatric Pneumology and Phtiseology Clinic SPAM, National Institute of Tuberculosis and Respiratory Diseases, 82556 Bratislava, Slovak Republic
  • Caragol, Isabel Pediatric Infectious Diseases Unit and Department of Immunology, Vall d'Hebron Hospital, 08035 Barcelona, Spain
  • Lammas, David MRC Center for Immune Regulation, The Medical School, University of Birmingham, Birmingham B15 2TT, United Kingdom
  • Kumararatne, Dinakantha S. Departments of Clinical Immunology and Medicine, Addenbrookes Hospital NHS Trust, Hill Road, Cambridge CB2 2QQ, United Kingdom
  • Abel, Laurent Laboratory of Human Genetics of Infectious Diseases, University René Descartes INSERM U550, Necker Medical School
  • Casanova, Jean-Laurent Pediatric Immunology and Hematology Unit, Necker Hospital
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  • 2003-2-17
Published in:
  • Journal of Experimental Medicine. - Rockefeller University Press. - 2003, vol. 197, no. 4, p. 527-535
Immunology
Immunology and Allergy
English The clinical phenotype of interleukin 12 receptor β1 chain (IL-12Rβ1) deficiency and the function of human IL-12 in host defense remain largely unknown, due to the small number of patients reported. We now report 41 patients with complete IL-12Rβ1 deficiency from 17 countries. The only opportunistic infections observed, in 34 patients, were of childhood onset and caused by weakly virulent Salmonella or Mycobacteria (Bacille Calmette-Guérin -BCG- and environmental Mycobacteria). Three patients had clinical tuberculosis, one of whom also had salmonellosis. Unlike salmonellosis, mycobacterial infections did not recur. BCG inoculation and BCG disease were both effective against subsequent environmental mycobacteriosis, but not against salmonellosis. Excluding the probands, seven of the 12 affected siblings have remained free of case-definition opportunistic infection. Finally, only five deaths occurred in childhood, and the remaining 36 patients are alive and well. Thus, a diagnosis of IL-12Rβ1 deficiency should be considered in children with opportunistic mycobacteriosis or salmonellosis; healthy siblings of probands and selected cases of tuberculosis should also be investigated. The overall prognosis is good due to broad resistance to infection and the low penetrance and favorable outcome of infections. Unexpectedly, human IL-12 is redundant in protective immunity against most microorganisms other than Mycobacteria and Salmonella. Moreover, IL-12 is redundant for primary immunity to Mycobacteria and Salmonella in many individuals and for secondary immunity to Mycobacteria but not to Salmonella in most.
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  • English
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bronze
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https://sonar.ch/global/documents/261175
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