Skip to main content

Advertisement

SpringerLink
Log in

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

  • Original Paper
  • Published:
European Journal of Pediatrics Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

IFNγ :

interferon gamma

IL :

interleukin

ISAAC :

International Study of Asthma and Allergy in Childhood

References

  1. Abbas AK, Murphy KM, Sher A (1996) Functional diversity of helper T lymphocytes. Nature 383: 787–793

    Article  PubMed  Google Scholar 

  2. Altare F, Jouanguy E, Lamhamedi-Cherradi S, Fondaneche MC, Fizame C, Ribierre F, Merlin G, Dembic Z, Schreiber R, Lisowska-Grospierre B, Fischer A, Seboun E, Casanova JL (1998) A causative relationship between mutant IFNgR1 alleles and impaired cellular response to IFNgamma in a compound heterozygous child. Am J Hum Genet 62: 723–726

    Article  PubMed  Google Scholar 

  3. Altare F, Durandy A, Lammas D, Emile JF, Lamhamedi S, Le Deist F, Drysdale P, Jouanguy E, Doffinger R, Bernaudin F, Jeppsson O, Gollob JA, Meinl E, Segal AW, Fischer A, Kumararatne D, Casanova JL (1998) Impairment of mycobacterial immunity in human interleukin-12 receptor deficiency. Science 280: 1432–1435

    Article  PubMed  Google Scholar 

  4. Altare F, Lammas D, Revy P, Jouanguy E, Doffinger R, Lamhamedi S, Drysdale P, Scheel-Toellner D, Girdlestone J, Darbyshire P, Wadhwa M, Dockrell H, Salmon M, Fischer A, Durandy A, Casanova JL, Kumararatne DS (1998) Inherited interleukin 12 deficiency in a child with Bacille Calmette-Guerin and Salmonella enteritidis disseminated infection. J Clin Invest 102: 2035–2040

    PubMed  Google Scholar 

  5. Asher MI, Weiland SK (1998) The International Study of Asthma and Allergies in Childhood (ISAAC). ISAAC Steeriing Committee. Clin Exp Allergy 28: 52–66; discussion 90–91

    Article  PubMed  Google Scholar 

  6. Asher MI, Keil U, Anderson HR, Beasley R, Crane J, Martinez F, Mitchell EA, Pearce N, Sibbald B, Stewart AW, Strachan D, Weiland S, Williams H (1995) International Study of Asthma and Allergies in Childhood (ISAAC): rationale and methods. Eur Respir J 8: 483–491

    Article  PubMed  Google Scholar 

  7. Bryan SA, O’Connor BJ, Matti S, Leckie MJ, Kanabar V, Khan J, Warrington SJ, Renzetti L, Rames A, Bock JA, Boyce MJ, Hansel TT, Holgate ST, Barnes PJ (2000) Effects of recombinant human interleukin-12 on eosinophils, airway hyper-responsiveness, and the late asthmatic response. Lancet 356: 2149–2153

    Article  PubMed  Google Scholar 

  8. Casanova JL, Abel L (2002) Genetic dissection of immunity to mycobacteria: the human model. Annu Rev Immunol 20: 581–620

    Article  PubMed  Google Scholar 

  9. Chatelain R, Varkila K, Coffman RL (1992) IL-4 induces a Th2 response in Leishmania major -infected mice. J Immunol 148: 1182–1187

    PubMed  Google Scholar 

  10. Coffman RL, Carty J (1986) A T cell activity that enhances polyclonal IgE production and its inhibition by interferon-gamma. J Immunol 136: 949–954

    PubMed  Google Scholar 

  11. Cookson WO, Young RP, Sandford AJ, Moffatt MF, Shirakawa T, Sharp PA, Faux JA, Julier C, Nakumuura Y, Nakumura Y, Lathrop.G. Hopkin J (1992) Maternal inheritance of atopic IgE responsiveness on chromosome 11q. Lancet 340: 381–384

    Article  PubMed  Google Scholar 

  12. Cousens LP, Peterson R, Hsu S, Dorner A, Altman JD, Ahmed R, Biron CA (1999) Two roads diverged: interferon alpha/beta- and interleukin 12-mediated pathways in promoting T cell interferon gamma responses during viral infection. J Exp Med 189: 1315–1328

    Article  PubMed  Google Scholar 

  13. Dalton DK, Pitts-Meek S, Keshav S, Figari IS, Bradley A, Stewart TA (1993) Multiple defects of immune cell function in mice with disrupted interferon-gamma genes. Science 259: 1739–1742

    PubMed  Google Scholar 

  14. De Jong R, Altare F, Haagen IA, Elferink DG, Boer T, van Breda Vriesman PJ, Kabel PJ, Draaisma JM, van Dissel JT, Kroon FP, Casanova JL, Ottenhoff TH (1998) Severe mycobacterial and Salmonella infections in interleukin-12 receptor-deficient patients. Science 280: 1435–1438

    Article  PubMed  Google Scholar 

  15. Doffinger R, Jouanguy E, Altare F, Wood P, Shirakawa T, Novelli F, Lammas D, Kumararatne D, Casanova JL (1999) Inheritable defects in interleukin-12- and interferon-gamma-mediated immunity and the TH1/TH2 paradigm in man. Allergy 54: 409–412

    Article  PubMed  Google Scholar 

  16. Dorman SE, Holland SM (1998) Mutation in the signal-transducing chain of the interferon-gamma receptor and susceptibility to mycobacterial infection. J Clin Invest 101: 2364–2369

    PubMed  Google Scholar 

  17. Dupuis S, Dargemont C, Fieschi C, Thomassin N, Rosenzweig S, Harris J, Holland SM, Schreiber RD, Casanova JL (2001) Impairment of mycobacterial but not viral immunity by a germline human STAT1 mutation. Science 293: 300–303

    Article  PubMed  Google Scholar 

  18. Fieschi C, Dupuis S, Picard C, Smith CI, Holland SM, Casanova JL (2001) High levels of interferon gamma in the plasma of children with complete interferon gamma receptor deficiency. Pediatrics 107: E48

    Article  PubMed  Google Scholar 

  19. Fieschi C, Dupuis S, Catherinot E, Feinberg J, Bustamante J, Breiman A, Altare F, Baretto R, Le Deist F, Kayal S, Koch H, Richter D, Brezina M, Aksu G, Wood P, Al-Jumaah S, Raspall M, Da Silva Duarte AJ, Tuerlinckx D, Virelizier JL, Fischer A, Enright A, Bernhoft J, Cleary AM, Vermylen C, Rodriguez-Gallego C, Davies G, Blutters-Sawatzki R, Siegrist CA, Ehlayel MS, Novelli V, Haas WH, Levy J, Freihorst J, Al-Hajjar S, Nadal D, De Moraes Vasconcelos D, Jeppsson O, Kutukculer N, Frecerova K, Caragol I, Lammas D, Kumararatne DS, Abel L, Casanova JL (2003) Low penetrance, broad resistance, and favorable outcome of interleukin 12 receptor beta1 deficiency: medical and immunological Implications. J Exp Med 197: 527–535

    Article  PubMed  Google Scholar 

  20. Gately MK, Renzetti LM, Magram J, Stern AS, Adorini L, Gubler U, Presky DH (1998) The interleukin-12/interleukin-12-receptor system: role in normal and pathologic immune responses. Annu Rev Immunol 16: 495–521

    Google Scholar 

  21. Gavett SH, O’Hearn DJ, Li X, Huang SK, Finkelman FD, Wills-Karp M (1995) Interleukin 12 inhibits antigen-induced airway hyperresponsiveness, inflammation, and Th2 cytokine expression in mice. J Exp Med 182: 1527–1536

    Article  PubMed  Google Scholar 

  22. Hogan SP, Foster PS, Tan X, Ramsay AJ (1998) Mucosal IL-12 gene delivery inhibits allergic airways disease and restores local antiviral immunity. Eur J Immunol 28: 413–423

    Article  PubMed  Google Scholar 

  23. Holland SM, Dorman SE, Kwon A, Pitha-Rowe IF, Frucht DM, Gerstberger SM, Noel GJ, Vesterhus P, Brown MR, Fleisher TA (1998) Abnormal regulation of interferon-gamma, interleukin-12, and tumor necrosis factor-alpha in human interferon-gamma receptor 1 deficiency. J Infect Dis 178: 1095–1104

    PubMed  Google Scholar 

  24. Huang S, Hendriks W, Althage A, Hemmi S, Bluethmann H, Kamijo R, Vilcek J, Zinkernagel RM, Aguet M (1993) Immune response in mice that lack the interferon-gamma receptor. Science 259: 1742–1745

    PubMed  Google Scholar 

  25. Janefjord CK, Jenmalm MC (2001) PHA-induced IL-12R beta(2) mRNA expression in atopic and non-atopic children. Clin Exp Allergy 31: 1493–1500

    Article  PubMed  Google Scholar 

  26. Jouanguy E, Altare F, Lamhamedi S, Revy P, Emile JF, Newport M, Levin M, Blanche S, Seboun E, Fischer A, Casanova JL (1996) Interferon-gamma-receptor deficiency in an infant with fatal Bacille Calmette-Guerin infection. N Engl J Med 335: 1956–1961

    Article  PubMed  Google Scholar 

  27. Jouanguy E, Lamhamedi-Cherradi S, Altare F, Fondaneche MC, Tuerlinckx D, Blanche S, Emile JF, Gaillard JL, Schreiber R, Levin M, Fischer A, Hivroz C, Casanova JL (1997) Partial interferon-gamma receptor 1 deficiency in a child with tuberculoid Bacillus Calmette-Guerin infection and a sibling with clinical tuberculosis. J Clin Invest 100: 2658–2664

    PubMed  Google Scholar 

  28. Jujo K, Renz H, Abe J, Gelfand EW, Leung DY (1992) Decreased interferon gamma and increased interleukin-4 production in atopic dermatitis promotes IgE synthesis. J Allergy Clin Immunol 90: 323–331

    PubMed  Google Scholar 

  29. Kaplan MH, Schindler U, Smiley ST, Grusby MJ (1996) Stat6 is required for mediating responses to IL-4 and for development of Th2 cells. Immunity 4: 313–319

    Article  PubMed  Google Scholar 

  30. Kips JC, Brusselle GG, Joos GF, Peleman RA, Devos RR, Tavernier JH, Pauwels RA (1995) Importance of interleukin-4 and interleukin-12 in allergen-induced airway changes in mice. Int Arch Allergy Immunol 107: 115–118

    PubMed  Google Scholar 

  31. Koppelman GH, Reijmerink NE, Colin Stine O, Howard TD, Whittaker PA, Meyers DA, Postma DS, Bleecker ER (2001) Association of a promoter polymorphism of the CD14 gene and atopy. Am J Respir Crit Care Med 163: 965–969

    PubMed  Google Scholar 

  32. Losana G, Rigamonti L, Borghi I, Assenzio B, Ariotti S, Jouanguy E, Altare F, Forni G, Casanova JL, Novelli F (2002) Requirement for both IL-12 and IFN-gamma signaling pathways in optimal IFN-gamma production by human T cells. Eur J Immunol 32: 693–700

    Article  PubMed  Google Scholar 

  33. Lu B, Ebensperger C, Dembic Z, Wang Y, Kvatyuk M, Lu T, Coffman RL, Pestka S, Rothman PB (1998) Targeted disruption of the interferon-gamma receptor 2 gene results in severe immune defects in mice. Proc Natl Acad Sci U S A 95: 8233–8238

    Article  PubMed  Google Scholar 

  34. Magram J, Sfarra J, Connaughton S, Faherty D, Warrier R, Carvajal D, Wu CY, Stewart C, Sarmiento U, Gately MK (1996) IL-12-deficient mice are defective but not devoid of type 1 cytokine responses. Ann N Y Acad Sci 795: 60–70

    PubMed  Google Scholar 

  35. Malmgaard L, Paludan SR (2003) Interferon (IFN)-alpha/beta, interleukin (IL)-12 and IL-18 coordinately induce production of IFN-gamma during infection with herpes simplex virus type 2. J Gen Virol 84: 2497–2500

    Article  PubMed  Google Scholar 

  36. Manetti R, Parronchi P, Giudizi MG, Piccinni MP, Maggi E, Trinchieri G, Romagnani S (1993) Natural killer cell stimulatory factor (interleukin 12 (IL-12)) induces T helper type 1 (Th1)-specific immune responses and inhibits the development of IL-4-producing Th cells. J Exp Med 177: 1199–1204

    Article  PubMed  Google Scholar 

  37. Matsui E, Kaneko H, Fukao T, Teramoto T, Inoue R, Watanabe M, Kasahara K, Kondo N (1999) Mutations of the IL-12 receptor beta2 chain gene in atopic subjects. Biochem Biophys Res Commun 266: 551–555

    Article  PubMed  Google Scholar 

  38. Matsui E, Kaneko H, Teramoto T, Fukao T, Inoue R, Kasahara K, Takemura M, Seishima M, Kondo N (2000) Reduced IFNgamma production in response to IL-12 stimulation and/or reduced IL-12 production in atopic patients. Clin Exp Allergy 30: 1250–1256

    Article  PubMed  Google Scholar 

  39. Matsumoto H, Suzuki K, Tsuyuguchi K, Tanaka E, Amitani R, Maeda A, Yamamoto K, Sasada M, Kuze F (1997) Interleukin-12 gene expression in human monocyte-derived macrophages stimulated with Mycobacterium bovis BCG: cytokine regulation and effect of NK cells. Infect Immun 65: 4405–4410

    PubMed  Google Scholar 

  40. Mountford AP, Coulson PS, Cheever AW, Sher A, Wilson RA, Wynn TA (1999) Interleukin-12 can directly induce T-helper 1 responses in interferon-gamma (IFN-gamma) receptor-deficient mice, but requires IFN-gamma signalling to downregulate T-helper 2 responses. Immunology 97: 588–594

    Article  PubMed  Google Scholar 

  41. Newport MJ, Huxley CM, Huston S, Hawrylowicz CM, Oostra BA, Williamson R, Levin M (1996) A mutation in the interferon-gamma-receptor gene and susceptibility to mycobacterial infection. N Engl J Med 335: 1941–1949

    Article  PubMed  Google Scholar 

  42. Ober C, Leavitt SA, Tsalenko A, Howard TD, Hoki DM, Daniel R, Newman DL, Wu X, Parry R, Lester LA, Solway J, Blumenthal M, King RA, Xu J, Meyers DA, Bleecker ER, Cox NJ (2000) Variation in the interleukin 4-receptor alpha gene confers susceptibility to asthma and atopy in ethnically diverse populations. Am J Hum Genet 66: 517–526

    Article  PubMed  Google Scholar 

  43. Ottenhoff TH, Kumararatne D, Casanova JL (1998) Novel human immunodeficiencies reveal the essential role of type-1 cytokines in immunity to intracellular bacteria. Immunol Today 19: 491–494

    Article  PubMed  Google Scholar 

  44. Pearce N, Weiland S, Keil U, Langridge P, Anderson HR, Strachan D, Bauman A, Young L, Gluyas P, Ruffin D, Crane J, Beasley R (1993) Self-reported prevalence of asthma symptoms in children in Australia, England, Germany and New Zealand: an international comparison using the ISAAC protocol. Eur Respir J 6: 1455–1461

    PubMed  Google Scholar 

  45. Picard C, Fieschi C, Altare F, Al-Jumaah S, Al-Hajjar S, Feinberg J, Dupuis S, Soudais C, Al-Mohsen IZ, Genin E, Lammas D, Kumararatne DS, Leclerc T, Rafii A, Frayha H, Murugasu B, Wah LB, Sinniah R, Loubser M, Okamoto E, Al-Ghonaium A, Tufenkeji H, Abel L, Casanova JL (2002) Inherited interleukin-12 deficiency: IL12B genotype and clinical phenotype of 13 patients from six kindreds. Am J Hum Genet 70: 336–348

    Article  PubMed  Google Scholar 

  46. Pierre-Audigier C, Jouanguy E, Lamhamedi S, Altare F, Rauzier J, Vincent V, Canioni D, Emile JF, Fischer A, Blanche S, Gaillard JL, Casanova JL (1997) Fatal disseminated Mycobacterium smegmatis infection in a child with inherited interferon gamma receptor deficiency. Clin Infect Dis 24: 982–984

    PubMed  Google Scholar 

  47. Prescott SL, Holt PG (1998) Abnormalities in cord blood mononuclear cytokine production as a predictor of later atopic disease in childhood. Clin Exp Allergy 28: 1313–1316

    Article  PubMed  Google Scholar 

  48. Prescott SL, Macaubas C, Smallacombe T, Holt BJ, Sly PD, Loh R, Holt PG (1998) Reciprocal age-related patterns of allergen-specific T-cell immunity in normal vs. atopic infants. Clin Exp Allergy 28 [Suppl 5]: 39–44; discussion 50–51

  49. Prescott SL, Macaubas C, Holt BJ, Smallacombe TB, Loh R, Sly PD, Holt PG (1998) Transplacental priming of the human immune system to environmental allergens: universal skewing of initial T cell responses toward the Th2 cytokine profile. J Immunol 160: 4730–4737

    PubMed  Google Scholar 

  50. Prescott SL, Macaubas C, Smallacombe T, Holt BJ, Sly PD, Holt PG (1999) Development of allergen-specific T-cell memory in atopic and normal children. Lancet 353: 196–200

    Article  PubMed  Google Scholar 

  51. Roesler J, Kofink B, Wendisch J, Heyden S, Paul D, Friedrich W, Casanova JL, Leupold W, Gahr M, Rosen-Wolff A (1999) Listeria monocytogenes and recurrent mycobacterial infections in a child with complete interferon-gamma-receptor (IFNgammaR1) deficiency: mutational analysis and evaluation of therapeutic options. Exp Hematol 27: 1368–1374

    Article  PubMed  Google Scholar 

  52. Seder RA, Gazzinelli R, Sher A, Paul WE (1993) Interleukin 12 acts directly on CD4+ T cells to enhance priming for interferon gamma production and diminishes interleukin 4 inhibition of such priming. Proc Natl Acad Sci U S A 90: 10188–10192

    PubMed  Google Scholar 

  53. Skeen MJ, Miller MA, Ziegler HK (1996) Interleukin-12 as an adjuvant in the generation of protective immunity to an intracellular pathogen. Ann N Y Acad Sci 795: 416–419

    PubMed  Google Scholar 

  54. Szabo SJ, Dighe AS, Gubler U, Murphy KM (1997) Regulation of the interleukin (IL)-12R beta 2 subunit expression in developing T helper 1 (Th1) and Th2 cells. J Exp Med 185: 817–824

    Article  PubMed  Google Scholar 

  55. Tang ML, Coleman J, Kemp AS (1995) Interleukin-4 and interferon-gamma production in atopic and non-atopic children with asthma. Clin Exp Allergy 25: 515–521

    PubMed  Google Scholar 

  56. Verhagen CE, de Boer T, Smits HH, Verreck FA, Wierenga EA, Kurimoto M, Lammas DA, Kumararatne DS, Sanal O, Kroon FP, van Dissel JT, Sinigaglia F, Ottenhoff TH (2000) Residual type 1 immunity in patients genetically deficient for interleukin 12 receptor beta1 (IL-12Rbeta1): evidence for an IL-12Rbeta1-independent pathway of IL-12 responsiveness in human T cells. J Exp Med 192: 517–528

    Article  PubMed  Google Scholar 

  57. Wang J, Wakeham J, Harkness R, Xing Z (1999) Macrophages are a significant source of type 1 cytokines during mycobacterial infection. J Clin Invest 103: 1023–1029

    PubMed  Google Scholar 

  58. Worldwide variations in the prevalence of asthma symptoms: the International Study of Asthma and Allergies in Childhood (ISAAC) (1998). Eur Respir J 12: 315–335

    Article  PubMed  Google Scholar 

  59. Worldwide variation in prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and atopic eczema: ISAAC. The International Study of Asthma and Allergies in Childhood (ISAAC) Steering Committee (1998). Lancet 351: 1225–1232

    Article  PubMed  Google Scholar 

  60. Wu C, Ferrante J, Gately MK, Magram J (1997) Characterization of IL-12 receptor beta1 chain (IL-12Rbeta1)-deficient mice: IL-12Rbeta1 is an essential component of the functional mouse IL-12 receptor. J Immunol 159: 1658–1665

    PubMed  Google Scholar 

  61. Yang X, Wang S, Fan Y, Zhu L (1999) Systemic mycobacterial infection inhibits antigen-specific immunoglobulin E production, bronchial mucus production and eosinophilic inflammation induced by allergen. Immunology 98: 329–337

    Article  PubMed  Google Scholar 

  62. Yang X, Fan Y, Wang S, Han X, Yang J, Bilenki L, Chen L (2002) Mycobacterial infection inhibits established allergic inflammatory responses via alteration of cytokine production and vascular cell adhesion molecule-1 expression. Immunology 105: 336–343

    Article  PubMed  Google Scholar 

  63. Yoshimoto T, Okamura H, Tagawa YI, Iwakura Y, Nakanishi K (1997) Interleukin 18 together with interleukin 12 inhibits IgE production by induction of interferon-gamma production from activated B cells. Proc Natl Acad Sci U S A 94: 3948–3953

    Article  PubMed  Google Scholar 

Download references

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.

Author information

Authors and Affiliations

  1. Department of Clinical Immunology and Allergy, St. James’s University Hospital, Beckett Street, Leeds, LS9 7TF, UK

    Philip M. D. Wood

  2. INSERM U550, Necker-Enfants Malades Medical School, Paris, France

    Claire Fieschi, Capucine Picard & Jean-Laurent Casanova

  3. Department of Immunohaematology and Blood Transfusion, Leiden University Medical Centre, Leiden, The Netherlands

    Tom H. M. Ottenhoff

  4. Unite d’Hematologie et d’Immunologie Pediatriques, Hopital Necker-Enfants Malades, Paris, France

    Jean-Laurent Casanova

  5. Department of Clinical Immunology, Addenbrookes Hospital, Cambridge, UK

    Dinakantha S. Kumararatne

Authors
  1. Philip M. D. Wood
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Claire Fieschi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Capucine Picard
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tom H. M. Ottenhoff
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jean-Laurent Casanova
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Dinakantha S. Kumararatne
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Philip M. D. Wood.

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00431-005-1745-5

Keywords

Search

Navigation