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Inherited defects in the interferon-gamma receptor or interleukin-12 signalling pathways are not sufficient to cause allergic disease in children

Abstract

T-helper (Th)2 cells, which produce the cytokines interleukins (IL)-4, IL-5 and IL-13, dominate T cell responses in allergic diseases. The Th1-type cytokines IL-12 and interferon-gamma (IFNγ) are important in down-regulating Th2 responses to allergens. Patients with defects in the IL-12 receptor (IL-12R) or IFNγ receptor (IFNγR) have abnormal responses to IL-12 or IFNγ and a failure to produce normal levels of IFNγ. Current paradigms of T-helper subset balance would predict a high prevalence of atopic illness in this group. We have studied a cohort of patients ( n =29) with defects in these pathways to assess the prevalence of allergic disease. A questionnaire based on those developed for the International Study of Asthma and Allergy in Childhood (ISAAC) was used in conjunction with analysis of total and specific IgE to common aeroallergens. The prevalence of asthma, eczema and rhino-conjunctivitis (13.7%, 17.5% and 6.8% respectively) in this group was no higher than in comparable populations where prevalences of 13.9%, 7.9% and 13.5% are reported for asthma, eczema and rhinoconjunctivitis respectively. Patients with IFNγR defects had higher rates of clinical atopic illness than control populations and patients with IL-12R defects, with 28.5% prevalences for asthma and eczema, respectively. None of the patients suffered from severe clinical atopic disease. Defects in interferon-gamma receptor/interleukin-12 receptor responses are not sufficient to cause clinical allergic disease. Patients with defects in the interferon-gamma receptor pathway have a higher prevalence of high IgE and clinical atopic illness compared to control populations, supporting the concept that interferon-gamma receptor signalling plays a role in down-regulating type-2 cytokine responses.

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Abbreviations

IFNγ :

interferon gamma

IL :

interleukin

ISAAC :

International Study of Asthma and Allergy in Childhood

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Acknowledgements

The authors would like to express their thanks for the continued participation of the patients, their families and those involved in their care in clinical and laboratory studies. This work was supported by grants from the FRM, Fondation Schlumberger, Sequella Foundation, Action Blanche Jeunes Chercheurs, and PNRMMIP to J-L. C, the Netherlands Leprosy Foundation and the Netherlands Organisation for Scientific Research to T. H. M. O. C. Fieschi is supported by the ARC.

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Correspondence to Philip M. D. Wood.

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Wood, P.M.D., Fieschi, C., Picard, C. et al. Inherited defects in the interferon-gamma receptor or interleukin-12 signalling pathways are not sufficient to cause allergic disease in children. Eur J Pediatr 164, 741–747 (2005). https://doi.org/10.1007/s00431-005-1745-5

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Keywords

  • Atopy
  • Interferon-gamma
  • Interleukin-12
  • Type 1 cytokine