FAMILIAL DISSEMINATED ATYPICAL MYCOBACTERIAL INFECTION IN CHILDHOOD -A HUMAN MYCOBACTERIAL SUSCEPTIBILITY GENE

Inherited defects in specific components of the immune system have pro vided many clues to the immunological mechanisms underlying resistance to microbial infection. We report a familial immune defect predisposi ng to disseminated atypical mycobacterial infection in childhood. 6 ch ildren with disseminated atypical mycobacterial infection and no recog nised form of immunodeficency were identified. Four, including two bro thers, come from a village in Malta, and two are brothers of Creek Cyp riot origin. They presented with fever, weight loss, lymphadenopathy, and hepatosplenomegaly. They had anaemia and an acute phase response. A range of different mycobacteria (Mycobacterium fortuitum, M chelonei , and four strains of M avium intracellulare complex) were isolated. T reatment with multiple antibiotics failed to eradicate the infection, although treatment with gamma interferon was associated with improveme nt. Three have died and the surviving children have chronic infection. Tumour necrosis factor-cr production in response to endotoxin and gam ma-interferon was found to be defective in affected patients and their parents. T-cell proliferative responses to mycobacterial and recall a ntigens were reduced in parents of affected children and gamma-interfe ron production was diminished in the affected patients and their paren ts. Clinical and immunological features suggest that these patients ar e phenotypically similar to Lsh/Ity/Bcg susceptible mice. Understandin g of this defect may provide insights into the mechanisms responsible for susceptibility to mycobacteria.