Low penetrance, broad resistance, and favorable outcome of interleukin 12 receptor beta1 deficiency: medical and immunological implications.
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.
Fieschi
Claire
C
Laboratory of Human Genetics of Infectious Diseases, University René Descartes INSERM U550, Necker Medical School, Paris, France.
Dupuis
Stéphanie
S
Catherinot
Emilie
E
Feinberg
Jacqueline
J
Bustamante
Jacinta
J
Breiman
Adrien
A
Altare
Frédéric
F
Baretto
Richard
R
Le Deist
Françoise
F
Kayal
Samer
S
Koch
Hartmut
H
Richter
Darko
D
Brezina
Martin
M
Aksu
Guzide
G
Wood
Phil
P
Al-Jumaah
Suliman
S
Raspall
Miquel
M
Da Silva Duarte
Alberto José
AJ
Tuerlinckx
David
D
Virelizier
Jean-Louis
JL
Fischer
Alain
A
Enright
Andrea
A
Bernhöft
Jutta
J
Cleary
Aileen M
AM
Vermylen
Christiane
C
Rodriguez-Gallego
Carlos
C
Davies
Graham
G
Blütters-Sawatzki
Renate
R
Siegrist
Claire-Anne
CA
Ehlayel
Mohammad S
MS
Novelli
Vas
V
Haas
Walther H
WH
Levy
Jacob
J
Freihorst
Joachim
J
Al-Hajjar
Sami
S
Nadal
David
D
De Moraes Vasconcelos
Dewton
D
Jeppsson
Olle
O
Kutukculer
Necil
N
Frecerova
Klara
K
Caragol
Isabel
I
Lammas
David
D
Kumararatne
Dinakantha S
DS
Abel
Laurent
L
Casanova
Jean-Laurent
JL
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
C508438:IL12RB1 protein, human; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12