Mycobacterium bovis BCG-itis and Cervical Lymphadenitis due to Salmonella enteritidis in a Patient with Complete Interleukin-12/-23 Receptor beta 1 Deficiency

Vosse, E. van de; Ottenhoff, T.H.M.; Paus, R.A. de; Verhard, E.M.; Boer, T. de; Dissel, J.T. van; Kuijpers, T.W.

Mendelian susceptibility to mycobacterial disease (MSMD) is a rare disorder with predisposition to severe, sometimes lethal, disease caused by otherwise poorly virulent, non-tuberculous environmental mycobacteria and poorly virulent salmonellae. In patients with MSMD, mutations have been identified in five genes that encode for the proteins IL-12/IL-23p40, IL-12/IL-23R beta 1, IFN-gamma R1, IFN-gamma R2 and STAT1. These proteins play important roles in the type-1 cytokine pathway, which is crucial for human host defence against intracellular pathogens such as mycobacteria and salmonellae. We report a girl with mild Mycobacterium bovis Bacille Calmette Guerin (BCG) disease and Salmonella enteritidis cervical lymphadenitis. Despite treatment, she has remained a fecal carrier of S. enteritidis for the past 14 years. She was found to have complete IL-12/IL-23R beta 1 deficiency. A homozygous r.518G>C IL12RB1 mutation was identified, leading to a non-functional R173P substitution in the...Show moreMendelian susceptibility to mycobacterial disease (MSMD) is a rare disorder with predisposition to severe, sometimes lethal, disease caused by otherwise poorly virulent, non-tuberculous environmental mycobacteria and poorly virulent salmonellae. In patients with MSMD, mutations have been identified in five genes that encode for the proteins IL-12/IL-23p40, IL-12/IL-23R beta 1, IFN-gamma R1, IFN-gamma R2 and STAT1. These proteins play important roles in the type-1 cytokine pathway, which is crucial for human host defence against intracellular pathogens such as mycobacteria and salmonellae. We report a girl with mild Mycobacterium bovis Bacille Calmette Guerin (BCG) disease and Salmonella enteritidis cervical lymphadenitis. Despite treatment, she has remained a fecal carrier of S. enteritidis for the past 14 years. She was found to have complete IL-12/IL-23R beta 1 deficiency. A homozygous r.518G>C IL12RB1 mutation was identified, leading to a non-functional R173P substitution in the IL-12/IL-23R beta 1 protein. This mutation abrogated IL-12/1L-23R beta 1 cell-surface expression and resulted in complete lack of T cell responsiveness to both IL-12 and IL-23.Show less

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Mycobacterium bovis BCG-itis and Cervical Lymphadenitis due to Salmonella enteritidis in a Patient with Complete Interleukin-12/-23 Receptor beta 1 Deficiency