Impaired Interferon Gamma-Mediated Immunity and Susceptibility to Mycobacterial Infection in Childhood
2001; Springer Nature; Volume: 50; Issue: 1 Linguagem: Inglês
10.1203/00006450-200107000-00005
ISSN1530-0447
AutoresNatascha Remus, Janine Reichenbach, Capucine Pïcard, Christoph Rietschel, Philip Wood, David A. Lammas, D Kumararatne, Jean‐Laurent Casanova,
Tópico(s)Immunodeficiency and Autoimmune Disorders
ResumoMendelian 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 (IFNγ) mediated immunity. The severity of the clinical phenotype depends on the genotype. Complete IL-12 p40 and IL-12 receptor β1 deficiencies and partial IFNγ receptor 1 (IFNγR1) and IFNγR2 deficiencies generally lead to curable infections at various ages, and antibiotics supplemented with IFNγ if required are likely to be effective. Complete IFNγR1 and IFNγR2 deficiencies predispose to overwhelming infection in early childhood, which may respond to antibiotics but relapse when antibiotics are discontinued. Rapid discrimination between complete IFNγR1 and IFNγR2 deficiency and other defects, therefore, is an important diagnostic step for planning clinical management.
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