Clinical disease caused by Klebsiella in 2 unrelated patients with interleukin 12 receptor beta1 deficiency

Abstract

Patients with interleukin 12 (IL-12)p40 or IL-12 receptor β1 (IL12Rβ1) deficiencies are prone to develop infections caused by mycobacteria and salmonella; other infections have only been rarely observed. In this report we describe 2 unrelated patients with complete autosomal recessive IL12Rβ1 deficiency who suffered from sepsis attributable to Klebsiella pneumoniae. A Mexican boy suffered from disseminated bacille Calmette-Guérin disease and infections caused by K pneumoniae and Candida albicans and had a fatal outcome. A Turkish girl living in France suffered from disseminated Nocardia nova infection and K pneumoniae sepsis. Therefore, Klebsiella infections should be considered in patients with IL12Rβ1 deficiency. Conversely, IL12Rβ1 deficiency should be considered in patients with unexplained klebsiellosis.

FIGURE 1

A, IFN-γ produced by stimulated whole-blood samples was undetectable in the patients, and they did not respond to IL-12. NS indicates not stimulated; P1, patient 1; P2, patient 2; M, mother of patient 1; PPD, purified protein derivative from M tuberculosis; C, healthy control. B, IL12Rβ1 was not expressed on PHA-T blasts, as assessed with 1 (patient 1, left) and 2 (patient 2, right) monoclonal antibodies. FL1-H indicates ●●●●●●; open histograms, IL12Rβ1; closed histograms, isotype controls. C, Family trees of the studied patients showing the mutations found. ND indicates not done; WT, wild type; arrows, patients; diagonal line, the person concerned is dead.

FIGURE 2

Simplified model of the immune response in a healthy individual and in a patient with a mutation in IL12RB1, lacking IL12Rβ1 expression. The hypothetical consequences of nonfunctional IL-12 receptor are depicted. This model is based on the clinical cases reported here and published articles on animal models of infection.