Atypical presentation of IL-12 receptor β1 deficiency with pneumococcal sepsis and disseminated nontuberculous mycobacterial infection in a 19-month-old girl born to nonconsanguineous US residents

Abstract

Atypical presentation of IL-12 receptor β1 deficiency with pneumococcal sepsis and disseminated nontuberculous mycobacterial infection in a 19-month-old girl born to nonconsanguineous US residents

Antimicrobial Susceptibility Testing, Drug Resistance Mechanisms, and Therapy of Infections with Nontuberculous Mycobacteria

“…Several reports have shown that patients who had defects in these pathways developed serious and sometimes fatal infections with MTBC and NTM (142,144,309).…”

“…Gruenberg and colleagues (142) described a second child who, at 19 months of age, was diagnosed with MAC and Streptococcus pneumoniae infection due to an IL-12R␤1 mutation (142). The case represented the first documented case of sepsis due to S. pneumoniae in a patient with an IL-12R␤1 deficiency.…”

IL-12Rβ1 Deficiency: Mutation Update and Description of theIL12RB1Variation Database

“…It has since been reported in patients from Argentina, Belgium, United States, Poland and the United Kingdom [Rosenzweig et al, 2006; Haerynck et al, 2008; Yancoski et al, 2009; Gruenberg et al, 2009; de Beaucoudrey et al, 2010]. A founder effect has been proposed for this mutation because its distribution is restricted to Europeans and to individuals from European ancestry living in former European colonies.…”

Intact IL-12 signaling is necessary for the generation of human natural killer cells with enhanced effector function after restimulation

“…In our opinion, the best method to address this issue would involve the use of PBMCs from patients with a deficiency in IL-12 or IL-12 receptor (IL-12R), since we could then exclude that the NK cells used in the experiments had been activated at any time in vivo by IL-12. We have previously described a 19-month-old patient with an IL-12Rβ1 deficiency due to a complex mutation at exon 14 in the IL12RB1 gene (c.1623_1624delinsTT; p.Q541X) (9). We showed that IFN-γ production was markedly decreased after stimulation of PBMCs with phytohemagglutinin (PHA) or PHA plus IL-12 and that there was diminished STAT4 phosphorylation after IL-12 stimulation (9).…”