Severe Mycobacterium bovis BCG infections in a large series of novel IL–12 receptor β1 deficient patients and evidence for the existence of partial IL–12 receptor β1 deficiency

Cell mediated immunity plays a critical role in human host defence against intracellular bacteria. In patients with unusual, severe infections caused by poorly pathogenic species of mycobacteria and salmonellae, genetic deficiencies have been identified in key genes in the type‐1 cytokine pathway, e...

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Published in:European journal of immunology 2003-01, Vol.33 (1), p.59-69
Main Authors: Lichtenauer‐Kaligis, Elgin G. R., de Boer, Tjitske, Verreck, Frank A. W., van Voorden, Sjaak, Hoeve, Marieke A., Vosse, Esther van de, Ersoy, Fugen, Tezcan, Ilhan, van Dissel, Jaap T., Sanal, Ozden, Ottenhoff, Tom H. M.
Format: Article
Language:English
Subjects:
Genetic mutation
Interleukin‐12 receptor
Mycobacterium bovis BCG
Partial IL–12R deficiency
Type‐1 cytokine
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Summary:Cell mediated immunity plays a critical role in human host defence against intracellular bacteria. In patients with unusual, severe infections caused by poorly pathogenic species of mycobacteria and salmonellae, genetic deficiencies have been identified in key genes in the type‐1 cytokine pathway, especially in IFNGR1 and IL12RB1. Here, we analyzed 11 patients originating from Turkey and suffering from unusual Mycobacterium bovis Bacille Calmette‐Guerin infections following vaccination, and found that most patients (n=8) are deficient in IL‐12Rβ1 expression and function. No defects were found in patients' IFN‐γR or IL‐18R. In addition, a first patient suffering from partial IL‐12Rβ1 deficiency is described. This patient presented with an intermediate cellular and immunological phenotype: a consistent, low response to IL‐12 was found, which could be further augmented by IL‐18. Despite a lack of cell surface IL‐12Rβ1 expression, normal levels of intracellular IL‐12Rβ1 protein were detectable, which was not seen in the other, completely IL‐12Rβ1 deficient patients examined. Moreover, this patient had a relatively mild clinical phenotype and was the only individual with a single homozygous amino acid substitution in IL‐12Rβ1 (C198R). Collectively, our findings indicate that idiopathic, unusually severe infections due to M. bovis BCG can be caused by complete as well as partial IL‐12Rβ1 deficiency.
ISSN:0014-2980
1521-4141
DOI:10.1002/immu.200390008