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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Impaired interferon gamma-mediated immunity and susceptibility to mycobacterial infection in childhood.

Mendelian susceptibility to poorly virulent mycobacteria such as bacillus Calmette-Guerin (BCG) and environmental nontuberculous mycobacteria is a clinically heterogeneous syndrome. The clinical features of affected children cover a continuous spectrum from disseminated lethal bacillus Calmette-Guerin infection to local recurrent nontuberculous mycobacterial infection. Different types of mutations in four genes (IFNGR1, IFNGR2, IL12B, IL12RB1) have revealed both allelic and nonallelic heterogeneity and result in eight different disorders whose common pathogenic pathway is impaired interferon gamma (IFNgamma) mediated immunity. The severity of the clinical phenotype depends on the genotype. Complete IL-12 p40 and IL-12 receptor beta1 deficiencies and partial IFNgamma receptor 1 (IFNgammaR1) and IFNgammaR2 deficiencies generally lead to curable infections at various ages, and antibiotics supplemented with IFNgamma if required are likely to be effective. Complete IFNgammaR1 and IFNgammaR2 deficiencies predispose to overwhelming infection in early childhood, which may respond to antibiotics but relapse when antibiotics are discontinued. Rapid discrimination between complete IFNgammaR1 and IFNgammaR2 deficiency and other defects, therefore, is an important diagnostic step for planning clinical management.[1]


  1. Impaired interferon gamma-mediated immunity and susceptibility to mycobacterial infection in childhood. Remus, N., Reichenbach, J., Picard, C., Rietschel, C., Wood, P., Lammas, D., Kumararatne, D.S., Casanova, J.L. Pediatr. Res. (2001) [Pubmed]
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