title: Mycobacterium bovis BCG-itis and cervical lymphadenitis due to Salmonella enteritidis in a patient with complete interleukin-12/-23 receptor beta1 deficiency.
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-23Rbeta1, IFN-R1, IFN-gammaR2 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-23Rbeta1 deficiency. A homozygous r.518G>C IL12RB1 mutation was identified, leading to a non-functional R173P substitution in the IL-12/IL-23Rbeta1 protein. This mutation abrogated IL-12/IL-23Rbeta1 cell-surface expression and resulted in complete lack of T cell responsiveness to both IL-12 and IL-23.
authors.affiliation: Department of Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands. E.van_de_Vosse@LUMC.nl
authors.forename: E
authors.initials: E
authors.lastname: van de Vosse
authors.forename: T H M
authors.initials: TH
authors.lastname: Ottenhoff
authors.forename: R A
authors.initials: RA
authors.lastname: de Paus
authors.forename: E M
authors.initials: EM
authors.lastname: Verhard
authors.forename: T
authors.initials: T
authors.lastname: de Boer
authors.forename: J T
authors.initials: JT
authors.lastname: van Dissel
authors.forename: T W
authors.initials: TW
authors.lastname: Kuijpers
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D053711:Interleukin-12 Receptor beta 1 Subunit / Q000172:deficiency* / Q000235:genetics; D008199:Lymphadenitis / Q000382:microbiology*; D009163:Mycobacterium bovis / Q000302:isolation & purification*; D017354:Point Mutation; D018123:Receptors, Interleukin / Q000172:deficiency* / Q000235:genetics; D012480:Salmonella Infections / Q000276:immunology / Q000382:microbiology*; D012477:Salmonella enteritidis / Q000302:isolation & purification*; D014376:Tuberculosis / Q000276:immunology / Q000382:microbiology*
chemical_list: C515500:IL23R protein, human; D053711:Interleukin-12 Receptor beta 1 Subunit; D018123:Receptors, Interleukin