Low penetrance, broad resistance, and favorable outcome of interleukin 12 receptor β1 deficiency: Medical and immunological implications

Claire Fieschi, Stéphanie Dupuis, Emilie Catherinot, Jacqueline Feinberg, Jacinta Bustamante, Adrien Breiman, Frédéric Altare, Richard Baretto, Françoise Le Deist, Samer Kayal, Hartmut Koch, Darko Richter, Martin Brezina, Guzide Aksu, Phil Wood, Suliman Al-Jumaah, Miquel Raspall, Alberto José Da Silva Duarte, David Tuerlinckx, Jean Louis VirelizierAlain Fischer, Andrea Enright, Jutta Bernhöft, Aileen M. Cleary, Christiane Vermylen, Carlos Rodriguez-Gallego, Graham Davies, Renate Blütters-Sawatzki, Claire Anne Siegrist, Mohammad S. Ehlayel, Vas Novelli, Walther H. Haas, Jacob Levy, Joachim Freihorst, Sami Al-Hajjar, David Nadal, Dewton De Moraes Vasconcelos, Olle Jeppsson, Necil Kutukculer, Klara Frecerova, Isabel Caragol, David Lammas, Dinakantha S. Kumararatne, Laurent Abel, Jean Laurent Casanova

    Research output: Contribution to journalArticlepeer-review

    264 Scopus citations


    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.

    Original languageEnglish
    Pages (from-to)527-535
    Number of pages9
    JournalJournal of Experimental Medicine
    Issue number4
    StatePublished - 17 Feb 2003


    • Immunodeficiency
    • Interferon γ
    • Interleukin 12 receptor
    • MycobacteriaSalmonella

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology


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