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Low Penetrance, Broad Resistance, and Favorable Outcome of Interleukin 12 Receptor β1 Deficiency: Medical and Immunological Implications
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...
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Published in: | The Journal of experimental medicine 2003-02, Vol.197 (4), p.527-535 |
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Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
Format: | Article |
Language: | English |
Online Access: | Get full text |
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Summary: | 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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ISSN: | 0022-1007 1540-9538 |
DOI: | 10.1084/jem.20021769 |