title: Low penetrance, broad resistance, and favorable outcome of interleukin 12 receptor beta1 deficiency: medical and immunological implications.
abstract: The clinical phenotype of interleukin 12 receptor beta1 chain (IL-12Rbeta1) 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-12Rbeta1 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-12Rbeta1 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.
authors.affiliation: Laboratory of Human Genetics of Infectious Diseases, University René Descartes INSERM U550, Necker Medical School, Paris, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Fieschi
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Dupuis
authors.forename: Emilie
authors.initials: E
authors.lastname: Catherinot
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Feinberg
authors.forename: Jacinta
authors.initials: J
authors.lastname: Bustamante
authors.forename: Adrien
authors.initials: A
authors.lastname: Breiman
authors.forename: Frédéric
authors.initials: F
authors.lastname: Altare
authors.forename: Richard
authors.initials: R
authors.lastname: Baretto
authors.forename: Françoise
authors.initials: F
authors.lastname: Le Deist
authors.forename: Samer
authors.initials: S
authors.lastname: Kayal
authors.forename: Hartmut
authors.initials: H
authors.lastname: Koch
authors.forename: Darko
authors.initials: D
authors.lastname: Richter
authors.forename: Martin
authors.initials: M
authors.lastname: Brezina
authors.forename: Guzide
authors.initials: G
authors.lastname: Aksu
authors.forename: Phil
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authors.lastname: Wood
authors.forename: Suliman
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authors.lastname: Al-Jumaah
authors.forename: Miquel
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authors.lastname: Raspall
authors.forename: Alberto José
authors.initials: AJ
authors.lastname: Da Silva Duarte
authors.forename: David
authors.initials: D
authors.lastname: Tuerlinckx
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Virelizier
authors.forename: Alain
authors.initials: A
authors.lastname: Fischer
authors.forename: Andrea
authors.initials: A
authors.lastname: Enright
authors.forename: Jutta
authors.initials: J
authors.lastname: Bernhöft
authors.forename: Aileen M
authors.initials: AM
authors.lastname: Cleary
authors.forename: Christiane
authors.initials: C
authors.lastname: Vermylen
authors.forename: Carlos
authors.initials: C
authors.lastname: Rodriguez-Gallego
authors.forename: Graham
authors.initials: G
authors.lastname: Davies
authors.forename: Renate
authors.initials: R
authors.lastname: Blütters-Sawatzki
authors.forename: Claire-Anne
authors.initials: CA
authors.lastname: Siegrist
authors.forename: Mohammad S
authors.initials: MS
authors.lastname: Ehlayel
authors.forename: Vas
authors.initials: V
authors.lastname: Novelli
authors.forename: Walther H
authors.initials: WH
authors.lastname: Haas
authors.forename: Jacob
authors.initials: J
authors.lastname: Levy
authors.forename: Joachim
authors.initials: J
authors.lastname: Freihorst
authors.forename: Sami
authors.initials: S
authors.lastname: Al-Hajjar
authors.forename: David
authors.initials: D
authors.lastname: Nadal
authors.forename: Dewton
authors.initials: D
authors.lastname: De Moraes Vasconcelos
authors.forename: Olle
authors.initials: O
authors.lastname: Jeppsson
authors.forename: Necil
authors.initials: N
authors.lastname: Kutukculer
authors.forename: Klara
authors.initials: K
authors.lastname: Frecerova
authors.forename: Isabel
authors.initials: I
authors.lastname: Caragol
authors.forename: David
authors.initials: D
authors.lastname: Lammas
authors.forename: Dinakantha S
authors.initials: DS
authors.lastname: Kumararatne
authors.forename: Laurent
authors.initials: L
authors.lastname: Abel
authors.forename: Jean-Laurent
authors.initials: JL
authors.lastname: Casanova
mesh_terms: D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007113:Immunity, Innate; D009154:Mutation; D009164:Mycobacterium Infections / Q000276:immunology; D009894:Opportunistic Infections / Q000276:immunology; D018807:Polymorphism, Single-Stranded Conformational; D018123:Receptors, Interleukin / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D053707:Receptors, Interleukin-12; D012480:Salmonella Infections / Q000276:immunology
chemical_list: C508438:IL12RB1 protein, human; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12