Genetic predisposition to mycobacterial infections in man

Selective susceptibility to poorly pathogenic mycobacteria, such as Bacille Calmette-Guerin vaccine and environmental non-tuberculous mycobacteria, wa s suspected to be a Mendelian disorder but its molecular basis remained elu sive. Recently, mutations in the interferon gamma receptor ligand-binding c hain, interferon gamma receptor signalling chain, interleukin 12 p40 subuni t, and interleukin 12 receptor beta 1 chain genes were identified in a numb er of patients with these mycobacterial infections. Dominant or recessive a lleles causing complete or partial cellular defects were found to define se ven different inheritable disorders. Although genetically distinct, these c onditions are immunologically related and highlight the essential role of i nterferon gamma-mediated immunity in the control of mycobacteria in man. Di agnosis is difficult because of the genetic and immunologic heterogeneity o f this syndrome; nevertheless it is vital because decisions on the most app ropriate treatment are best taken based on an accurate molecular diagnosis. (C) 2000 Editions scientifiques et medicales Elsevier SAS.