Interleukin-12 receptor beta 1 deficiency in a patient with abdominal tuberculosis

Two siblings with interleukin-12 receptor beta1 (IL-12 beta1) deficiency bu t different clinical phenotypes were studied. Both are homozygous for an IL 12RB1 missense mutation that prevents receptor expression and abolishes cel lular responses to IL-12. Transfection of the patients' T cells with wild-t ype IL12RB1 restored IL-12R beta1 expression and function. One patient had the expected phenotype of disseminated bacille Calmette-Guerin (BCG) infect ion in early childhood, whereas the other did not develop BCG infection, de spite 3 inoculations with live BCG. Abdominal tuberculosis was diagnosed in this second patient at age 18 years. To date, neither of them has had clin ical disease caused by environmental mycobacteria. These observations show unexpected interfamilial and intrafamilial heterogeneity of the clinical ph enotype associated with IL-12R beta1 deficiency. The patients may be resist ant to BCG but remain vulnerable to Mycobacterium tuberculosis. A diagnosis of IL-12R beta1 deficiency should therefore be considered in selected pati ents with severe tuberculosis, despite their resistance to BCG and a lack o f atypical mycobacteriosis.