Clinical Tuberculosis in 2 of 3 Siblings with Interleukin-12 Receptor  1 Deficiency

Abstract

We describe 3 siblings with interleukin-12 receptor beta1 (IL-12Rbeta1) deficiency, a known genetic etiology of clinical disease caused by infection with poorly virulent mycobacteria, such as mycobacteria found in bacille Calmette-Guérin (BCG) vaccines and environmental nontuberculous mycobacteria (NTM). One child had disseminated tuberculosis, the second had extraintestinal salmonellosis and pulmonary tuberculosis, and the third remained asymptomatic. IL-12Rbeta1 deficiency should be considered as a diagnosis in patients with severe salmonellosis or tuberculosis, even if they do not have disease due to BCG or NTM.

Severe infectious diseases of childhood as monogenic inborn errors of immunity

“…These observations raise fundamental questions about the mechanisms underlying incomplete penetrance and variable expressivity that have yet to be answered. In this context, we serendipitously discovered the first cases (to our knowledge) of monogenic tuberculosis, in patients and even in families with IL-12Rβ1 deficiency manifesting solely as severe tuberculosis (86)(87)(88)(89)(90)(91). These patients were normally resistant to live bacillus Calmette-Guérin vaccine and environmental mycobacteria.…”

Immunity to Microbes: Lessons from Primary Immunodeficiencies

“…There are differences in susceptibility to mycobacteria with different PIDs. In patients with IL-12/IL-23-IFN-␥ axis defects, BCG and NTM are the most frequently identified, but there are also reports of Mycobacterium tuberculosis infections in this group (14,33,36,42,85,96). In CGD, BCG and M. tuberculosis have been isolated from patients living in areas where these diseases are endemic (1, 15, 63, 65, 74), whereas BCG has been the pre- dominant mycobacterium isolated from SCID patients (11,12,105) and NTM is the most common in children affected by NEMO defects (83) and idiopathic CD4 lymphocytopenia (45,103).…”

A novel X-linked recessive form of Mendelian susceptibility to mycobaterial disease

“…5 The patients are also vulnerable to the more virulent Mycobacterium tuberculosis. [6][7][8][9][10][11] Typically, patients are not particularly prone to other infections, except salmonellosis, which affects less than half the cases. MSMD is clinically heterogeneous, and outcome is correlated with the type of histological lesions present.…”