Here, we report a novel mutation in the IL-12Rβ1 gene in a female Pakistani patient who was born in a consanguineous marriage and developed severe bacille Calmette-Guérin (BCG) infection and recurrent tuberculosis.
Our report recalls the need of pediatricians in countries with TB-prevalence and high parental consanguinity, to consider <i>IL12RB1</i> deficiency in the differential diagnosis of a child with clinical evidence of TB, especially with the history of disseminated BCG disease.
Inherited IL-12Rβ1 and TYK2 deficiencies impair both IL-12- and IL-23-dependent IFN-γ immunity and are rare monogenic causes of tuberculosis, each found in less than 1/600,000 individuals.
Here, we report three cases referred to the Immunology, Asthma and Allergy ward at the National Research Institute of Tuberculosis and Lung Diseases (NRITLD) at Masih Daneshvari Hospital from 2012 to 2017 with Mycobacterium tuberculosis and non-tuberculous mycobacteria infections due to defects in IL-12Rβ1 but with different clinical manifestations.
Severe Enteropathy and Hypogammaglobulinemia Complicating Refractory Mycobacterium tuberculosis Complex Disseminated Disease in a Child with IL-12Rβ1 Deficiency.
Despite the small sample studied, our findings suggest that IL-12Rβ1 deficiency is not a very rare cause of pediatric tuberculosis in these countries, where it should be considered in selected children with severe disease.
Association studies on four non-synomymous cSNPs of IL12RB1 (641A/G, 1094T/C, 1132C/G, 1573G/A) in linkage disequilibrium showed that three of them (641A/G, 1094T/C, 1132C/G) were significantly associated with the development of TB.
In combination with prior studies showing increased production of TGF-beta by blood monocytes from tuberculosis patients, this suggests that increased TGF-beta production is the underlying abnormality that reduces IL-12R beta 1 and IL-12R beta 2 expression in tuberculosis.