Abstract
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-23Rβ1, IFN-コR1, IFN-γR2 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–Guérin (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-23Rβ1 deficiency. A homozygous r.518G>C IL12RB1 mutation was identified, leading to a non-functional R173P substitution in the IL-12/IL-23Rβ1 protein. This mutation abrogated IL-12/IL-23Rβ1 cell-surface expression and resulted in complete lack of T cell responsiveness to both IL-12 and IL-23.
Similar content being viewed by others
References
van de Vosse E, de Paus RA, van Dissel JT, Ottenhoff THM: Molecular complementation of IL-12Rß1 deficiency reveals functional differences between IL-12Rß1 alleles including partial IL-12Rß1 deficiency. Hum Mol Genet 2005; 14: 3847–3855.
van de Vosse E, Hoeve MA, Ottenhoff THM: Human genetics of intracellular infectious diseases: molecular and cellular immunity against mycobacteria and salmonellae. Lancet Infect Dis 2004; 4: 739–749.
van de Vosse E, Ottenhoff THM: Human host genetic factors in mycobacterial and Salmonella infection: lessons from single gene disorders in IL-12/IL-23-dependent signaling that affect innate and adaptive immunity. Microbes Infect 2006; 8: 1167–1173.
Aksu G, Tirpan C, Cavusoglu C, Soydan S, Altare F, Casanova JL, Kutukculer N: Mycobacterium fortuitum-chelonae complex infection in a child with complete interleukin-12 receptor beta 1 deficiency. Pediatr Infect Dis J 2001; 20: 551–553.
Altare F, Ensser A, Breiman A, Reichenbach J, El Baghdadi JE, Fischer A, Emile JF, Gaillard JL, Meinl E, Casanova JL: Interleukin-12 receptor ß1 deficiency in a patient with abdominal tuberculosis. J Infect Dis 2001; 184: 231–236.
Özbek N, Fieschi C, Yilmaz BT, de Beaucoudrey L, Demirham B, Feinberg J, Bikmaz YE, Casanova JL: Interleukin-12 receptor b1 chain deficiency in a child with disseminated tuberculosis. Clin Infect Dis 2005; 40: e55–e58.
Sanal O, Turul T, de Boer T, van de Vosse E, Yalcin I, Tezcan I, Sun C, Memis L, Ottenhoff THM, Ersoy F: Presentation of interleukin-12/-23 receptor ß1 deficiency with various clinical symptoms of Salmonella infections. J Clin Immunol 2006; 26: 1–6.
Ozen M, Ceyhan M, Sanal O, Bayraktar M, Mesci L: Recurrent Salmonella bacteremia in interleukin-12 receptor b1 deficiency. J Trop Pediatr 2006; 52: 296–298.
Tanir G, Dogu F, Tuygun N, Ikinciogullari A, Aytekin C, Aydemir C, Yuksek M, Boduroglu EC, de Beaucoudrey L, Fieschi C, Feinberg J, Casanova JL, Babacan E: Complete deficiency of the IL-12 receptor ß1 chain: three unrelated Turkish children with unusual clinical features. Eur J Pediatr 2006; 165: 415–417.
Kutukculer N, Genel F, Aksu G, Karapinar B, Ozturk C, Cavusoglu C, Casanova JL, Fieschi C: Cutaneous leukocytoclastic vasculitis in a child with interleukin-12 receptor beta-1 deficiency. J Pediatr 2006; 148: 407–409.
Rosenzweig SD, Yancoski J, Bernasconi A, Krasovec S, Marciano BE, Casimir L, Berberian G, Simboli N, Rousseau M, Calle G: Thirteen years of culture-positive M. bovis-BCG infection in an IL-12Rß1 deficient patient: Treatment and outcome. J Infect 2006; 52: e69–e72.
de Moraes-Vasconcelos D, Grumach AS, Yamaguti A, Andrade MEB, Fieschi C, de Beaucoudrey L, Casanova JL, Duarte AJS: Paracoccidioides brasiliensis disseminated disease in a patient with inherited deficiency in the ß1 subunit of the Interleukin (IL)-12/IL-23 receptor. Clin Infect Dis 2005; 41: e31–e37.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
van de Vosse, E., Ottenhoff, T.H.M., de Paus, R.A. et al. Mycobacterium bovis BCG-itis and Cervical Lymphadenitis due to Salmonella enteritidis in a Patient with Complete Interleukin-12/-23 Receptor β1 Deficiency. Infection 38, 128–130 (2010). https://doi.org/10.1007/s15010-009-9222-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s15010-009-9222-0