Skip to main content

Advertisement

SpringerLink
Log in

The role of allergens in the induction of asthma

  • Published:
Current Allergy and Asthma Reports Aims and scope Submit manuscript

Abstract

Despite the strong and consistent association between immediate hypersensitivity and asthma, there is still controversy about the role inhaled allergens play and about the timing of events related to sensitization. Recent studies have provided further evidence on the nature of the immune response to allergens, the timing of this response, and, in particular, whether any response to allergens occurs in utero. Some of the studies also provide a better explanation for why there is not a simple dose response relationship between allergens and asthma. The new studies also raise major issues about the nature of the immune response in nonallergic individuals. Taken together, the findings do not support a simple view about the balance between TH1 and TH2 responses, but strongly support the relevance of IgE to the risk of asthma.

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

References and Recommended Reading

  1. Woodfolk JA, Platts-Mills TAE: Allergens. In Samter’s Immunologic Diseases, edn. 6. Edited by Austen KF, Atkinson C. Baltimore: Lippincott Williams & Williams; 2001:787–810.

    Google Scholar 

  2. Tovey ER, Chapman MD, Platts-Mills TAE: Mite faeces are a major source of house dust allergens. Nature 1981, 289:592–593.

    Article  PubMed  CAS  Google Scholar 

  3. Luczynska CM, Li Y, Chapman MD, Platts-Mills TAE: Airborne concentrations and particle size distribution of allergen derived from domestic cats (Felis domesticus). Measurements using cascade impactor, liquid impinger, and a two-site monoclonal antibody assay for Fel d I. Amer Rev Respir Dis 1990, 141:361–367.

    CAS  Google Scholar 

  4. Sporik RB, Arruda LK, Woodfolk J, et al.: Environmental exposure to Aspergillus fumigatus allergen (Asp f I). Clin Exp Allergy 1993, 23:326–331.

    Article  PubMed  CAS  Google Scholar 

  5. Platts-Mills TAE, Vervloet D, Thomas WR, et al.: Indoor allergens and asthma. Third International Workshop, Cuenca, Spain. J Allergy Clin Immunol 1997, 100:S1-S24.

    Article  Google Scholar 

  6. Sporik R, Chapman MD, Platts-Mills TAE: House dust mite exposure as a cause of asthma [see comments] [review]. Clin Exp Allergy 1992, 22:897–906.

    Article  PubMed  CAS  Google Scholar 

  7. Platts-Mills TAE, Mitchell EB, Tovey ER, et al.: Airborne allergen exposure, allergen avoidance and bronchial hyperreactivity. In Asthma: Physiology, Immunopharmacology and Treatment, Third International Symposium. Edited by Kay AB, Austen KF, Lichtenstein LM. London: Academic Press; 1984:297–314.

    Google Scholar 

  8. Crater SE, Platts-Mills TAE: Searching for the cause of the increase in asthma [review]. Curr Opin Pediatr 1998, 10:594–599.

    PubMed  CAS  Google Scholar 

  9. Gerrard J, Geddes C, Reggin P, et al.: Serum IgE levels in white and Metis communities in Saskatchewan. Ann Allergy 1976, 37:91–100.

    PubMed  CAS  Google Scholar 

  10. Strachan DP, Taylor EM, Carpenter RG: Family structure, neonatal infection, and hay fever in adolescence. Arch Dis Child 1996, 74:422–426.

    PubMed  CAS  Google Scholar 

  11. Seaton A, Godden DJ, Brown K: Increase in asthma: a more toxic environment or a more susceptible population? Thorax 1994, 49:171–174.

    PubMed  CAS  Google Scholar 

  12. Platts-Mills TAE, Sporik RB, Chapman MD, Heymann PW: The role of domestic allergens [review]. Ciba Found Symp 1997, 206:173–185; discussion 185–189.

    PubMed  CAS  Google Scholar 

  13. Camargo CA Jr, Field AE, Coldritz GA, Speizer FE: Body mass index and asthma in children age 9–14. Am J Respir Crit Care Med 1999, 159:A150.

    Google Scholar 

  14. Luder E, Melnik TA, DiMaio M: Association of being overweight with greater asthma symptoms in inner city Black and Hispanic children. J Pediatr 1998, 132:699–703.

    Article  PubMed  CAS  Google Scholar 

  15. Kapsali T, Permutt S, Laube B, et al.: Potent bronchoprotective effect of deep inspiration and its absence in asthma. J Appl Physiol 2000, 89:711–720. Further evidence that patients with asthma respond inadequately to a deep inspiration. Although the experiments continue to show that the harmful effects of prolonged shallow breathing can be rapidly reversed, the experiments raise several important questions. If an allergic subject persistently breathes shallowly, will he or she develop persistent bronchial reactivity, and will prolonged full expansion of the lungs help to reverse these physiologic changes in asthma?

    PubMed  CAS  Google Scholar 

  16. Ishizaka K, Ishizaka T, Hornbrook MM: Allergen-binding activity of gamma-E, gamma-G, and gamma-A antibodies in sera from atopic patients. In vitro measurements of reaginic antibody. J Immunol 1967, 98:490–501.

    PubMed  CAS  Google Scholar 

  17. Platts-Mills TAE: Local production of IgG, IgA and IgE antibodies in grass pollen hay fever. J Immunol 1979, 122:2218–2225.

    PubMed  CAS  Google Scholar 

  18. Wierenga EA, Snoek M, DeGroot C, et al.: Evidence for compartmentalization of functional subsets of CD4+ lymphocytes in atopic patients. J Immunol 1990, 144:4651–4656.

    PubMed  CAS  Google Scholar 

  19. Werhoef A, Lamb JR: Threshold signaling of human Th0 cells in activation and anergy: modulation of effector function by altered TCR ligand. J Immunol 2000, 164:6034–6040.

    Google Scholar 

  20. Lichtenstein LM: An evaluation of the role of immunotherapy in asthma. Am Rev Respir Dis 1978, 117:191–197.

    PubMed  CAS  Google Scholar 

  21. Peat JK, Tovey E, Toelle BG, et al.: House dust mite allergens. A major risk factor for childhood asthma in Australia. Am J Respir Crit Care Med 1996, 153:141–146.

    PubMed  CAS  Google Scholar 

  22. Sporik R, Holgate ST, Platts-Mills TAE, Cogswell JJ: Exposure to house-dust mite allergen (Der p I) and the development of asthma in childhood. A prospective study. N Engl J Med 1990, 323:502–507.

    Article  PubMed  CAS  Google Scholar 

  23. Boner AL, Peroni D, Sette L, et al.: Effects of allergen exposure-avoidance on inflammation in asthmatic children. Allergy 1993, 48:119–123.

    Article  PubMed  CAS  Google Scholar 

  24. Haselden BM, Kay B, Larché M: Immunoglobulin E-independent major histocompatibility complex-restricted T cell peptide epitope-induced late asthmatic reactions. J Exp Med 1999, 189:1885–1894. Using peptides of Fel d 1, Dr. Larché and his colleagues provide strong evidence that there are allergen-specific T cells in the lungs. Interestingly, these delayed responses are not accompanied by a cellular infiltrate. The results raise various questions, including whether these T cells play a role in naturally occurring asthma and whether comparable T cells are present in nonallergic subjects or subjects with high exposure who have IgG ab to Fel d 1 (see reference [43]).

    Article  PubMed  CAS  Google Scholar 

  25. Rawle FC, Mitchell EB, Platts-Mills TAE: T cell responses to the major allergen from the house dust mite Dermatophagoides pteronyssinus, antigen P1: comparison of patients with asthma, atopic dermatitis, and perennial rhinitis. J Immunol 1984, 133:195–201.

    PubMed  CAS  Google Scholar 

  26. Upham JW, Holt BJ, Baron-Hay MJ, et al.: Allergen-specific T-cell reactivity is detectable in close to 100% of atopic and normal individuals: covert responses are unmasked by serum-free medium. Clin Exp Allergy 1995, 25:634–642.

    Article  PubMed  CAS  Google Scholar 

  27. Woodfolk JA, Sung SSJ, Benjamin DC, et al.: Distinct human T cell repertoires mediate immediate and delayed-type hypersensitivity to the Trichophyton antigen, Tri r 2. J Immunol 2000, 165:4379–4387.

    PubMed  CAS  Google Scholar 

  28. Woodfolk JA, Platts-Mills TAE: Diversity of the human allergen-specific T cell repertoire associated with distinct skin test reactions: DTH-associated major epitopes induce Th1- and Th2-dominated responses. J Immunol 2001, 167:5412–5419.

    PubMed  CAS  Google Scholar 

  29. Rakes GP, Arruda E, Ingram JM, et al.: Rhinovirus and respiratory syncytial virus in wheezing children requiring emergency care. IgE and eosinophil analyses. Amer J Resp Crit Care Med 1999, 159:785–790.

    CAS  Google Scholar 

  30. Rowntree S, Cogswell JJ, Platts-Mills TAE, Mitchell EB: Development of IgE and IgG antibodies to food and inhalant allergens in children at risk of allergic disease. Arch Dis Child 1985, 60:727–735.

    Article  PubMed  CAS  Google Scholar 

  31. Ball TM, Castro-Rodriguez JA, Griffith KA, et al.: Siblings, daycare attendance, and the risk of asthma and wheezing during childhood. N Engl J Med 2000, 343:538–543. In this analysis of the effects of early childhood infections, the authors identify a major discrepancy between different forms of infection. Children who had multiple nasal infections had a decreased risk of asthma at age 7 years. By contrast, children who had lower respiratory infections had an increased risk of asthma at age 7 years. The authors imply that the upper infections (but not the lower) could have shifted responses towards the TH1 pattern. However, they appear to resist the alternative explanation that lower respiratory infections identify children whose lungs will react, and thus will become asthmatic. If viral infections that give rise to lower infection are excluded, one might expect a selective decrease in asthma among the remainder. As with most studies of this kind, the authors provide no evidence to support a systematic shift to TH1 responses. In particular, there is no antibody data or evidence of delayed hypersensitivity.

    Article  PubMed  CAS  Google Scholar 

  32. Miles EA, Warner JA, Jones AC, et al.: Peripheral blood mononuclear cell proliferative responses in the first year of life in babies born to allergic parents. Clin Exp Allergy 1996, 26:780–788.

    Article  PubMed  CAS  Google Scholar 

  33. Prescott SL, Macaubas C, Holt BJ, et al.: Transplacental priming of the human immune system to environmental allergens: universal skewing of initial T cell responses toward the Th2 cytokine profile. J Immunol 1998, 160:4730–4737.

    PubMed  CAS  Google Scholar 

  34. Szepfalusi Z, Pichler J, Elsasser S, et al.: Transplacental priming of the human immune system with environmental allergens can occur early in gestation. J Allergy Clin Immunol 2000, 106:530–536. A major body of work on the in vitro response of cord blood lymphocytes. Despite the authors’ conclusions, the data show great variability and almost no association between exposure of the mother during pregnancy and the in vitro response to pollen antigens. Equally, the evidence does not support the idea that sensitization occurs early in pregnancy. (See reference [37] for full review.)

    Article  PubMed  CAS  Google Scholar 

  35. Chan-Yeung M, Ferguson A, Chan H, et al.: Umbilical cord blood mononuclear cell proliferative response to house dust mite does not predict the development of allergic rhinitis and asthma. J Allergy Clin Immunol 1999, 104:317–321.

    Article  PubMed  CAS  Google Scholar 

  36. Warner JO: The prediction and prevention of childhood asthma. In Asthma—A Link Between Environment, Immunology and the Airways. Edited by Neffen HE, Baena-Cagnani CE, Fabbi L, et al. Seattle: Hogrefe & Huber; 1999:22–26.

    Google Scholar 

  37. Platts-Mills TAE, Woodfolk JA: Cord blood proliferative responses to inhaled allergens: Is there a phenomenon [editorial]? J Allergy Clin Immunol 2000, 106:441–443.

    Article  PubMed  CAS  Google Scholar 

  38. Hesselmar B, Aberg N, Aberg B, et al.: Does early exposure to cat or dog protect against later allergen development? Clin Exp Allergy 1999, 29:611–617.

    Article  PubMed  CAS  Google Scholar 

  39. Ronmark E, Jonsson E, Platts-Mills T, et al.: Incidence and remission of asthma in schoolchildren: report from the obstructive lung disease in northern Sweden studies. Pediatrics 2001, 107:E37.

    Article  PubMed  CAS  Google Scholar 

  40. Roost HP, Kunzli N, Schindler C, et al.: Role of current and childhood exposure to cat and atopic sensitization. J Allergy Clin Immunol 1999, 104:941–947.

    Article  PubMed  CAS  Google Scholar 

  41. Melen E, Wickman M, Nordvall S, et al.: Influence of early and current environmental exposure factors on sensitization and outcome of asthma in preschool children. Allergy 2001, 56:646–652. Studying a cohort of allergic asthmatic children, the authors demonstrate very convincingly that a history of early exposure to animals correlates with immediate hypersensitivity to dander allergens and increased asthma. The authors argue that their results demonstrate that high exposure to cat allergens is harmful. However, by studying asthmatics, they have avoided the children who would have become tolerant, and the results give no guidance as to the population effects of high exposure. On the other hand, finding that sensitization is associated with increased risk is in keeping with all other studies (see references [39,43,49]).

    Article  PubMed  CAS  Google Scholar 

  42. Sears MR, Hervison GP, Holdaway MD, et al.: The relative risks of sensitivity to grass pollen, house dust mite, and cat dander in the development of childhood asthma. Clin Exp Allergy 1989, 19:419–424.

    Article  PubMed  CAS  Google Scholar 

  43. Platts-Mills TAE, Vaughan J, Squillace S, et al.: Sensitisation, asthma, and a modified Th2 response in children exposed to cat allergen: a population-based cross-sectional study. Lancet 2001, 357:752–756. Our study on middle-school children confirms the now wellestablished observation that children exposed to a high concentration of cat allergen have a decreased prevalence of sensitization to cat allergens. In addition, the study demonstrates for the first time that many of these children have made a different form of immune response: IgG and IG4 ab to Fel d 1 without allergy. This implies that it is the IgE ab that creates the risk of asthma and also provides further evidence against the notion that nonallergic individuals make T cell responses to allergens.

    Article  PubMed  CAS  Google Scholar 

  44. Perzanowski MS, Ronmark E, Platts-Mills TAE, Lundback B: The protective effect of living with a cat on developing asthma in pre-teenage children. 2001, in press.

  45. Muller UR, Adkis AC, Fricker M, et al.: Successful immunotherapy with T-cell epitope peptides of bee venom phospholipase A2 induces specific T-cell anergy in bee sting allergic patients. J Allergy Clin Immunol 1998, 101:747–754.

    Article  PubMed  CAS  Google Scholar 

  46. Aalberse RC, van der Gaag R, van Leeuwen J: Serologic aspects of IgG4 antibodies. I. Prolonged immunization results in an IgG4-restricted response. J Immunol 1983, 130:722–726.

    PubMed  CAS  Google Scholar 

  47. Zhang K, Mills FC, Saxon A: Switch cycles from IL-4 directed epsilon class switching from human B lymphocytes. J Immunol 1994, 152:3427–3435.

    PubMed  CAS  Google Scholar 

  48. Lau S, Illi S, Sommerfeld C, et al.: Early exposure to house-dust mite and cat allergens and development of childhood asthma: a cohort study. Multicentre Allergy Study Group. . Lancet 2000, 356:1392–1397. Dr. Lau and her colleagues in the MAS study provide evidence that a) the concentration of allergen predicts sensitization and b) sensitization is a major risk factor for asthma. As we discussed previously, the effect of sensitization would tend to obscure any dose response between allergen and asthma. Surprisingly, the authors do not find any suppressive effect of high-dose cat allergen. However, the study is marked by very low exposure to cat allergen (the 75th percentile for cat allergen starts at 220 ng/g!).

    Article  PubMed  CAS  Google Scholar 

  49. Platts-Mills TA, Sporik RB, Wheatley LM, Heymann PW: Is there a dose-response relationship between exposure to indoor allergens and symptoms of asthma [editorial] [review]? J Allergy Clin Immunol 1995, 96:435–440.

    Article  PubMed  CAS  Google Scholar 

  50. Custovic A, Hallam C. Simpson B, et al.: Decreased risk of sensitization to cats with high exposure to cat allergen. J Allergy Clin Immunol 2001, in press.

  51. Gereda JE, Klinnert MD, Price MR, et al.: Metropolitan home living conditions associated with indoor endotoxin levels. J Allergy Clin Immunol 2001, 107:790–796. More evidence showing an interrelationship between endotoxin and animals in the home. As with previous results, the relationship was not consistently with cat or dogs, but more with the presence of animals. The results raise important questions about whether endotoxin can influence the response to inhalant allergens. Although there is a general assumption that endotoxin would enhance TH1 response, this product of gram-negative bacteria also will enhance IL-10 production, which can help shift response from IgG4+ IgE to IgG4 (see references [43,45]).

    Article  PubMed  CAS  Google Scholar 

  52. Crater DD, Heise S, Perzanowski M, et al.: Asthma hospitaliza-tion trends in Charleston, South Carolina, from 1956–1997: twenty-fold increase among African-American children over a thirty-year period. Pediatrics 2001, in press. Dr. Crater and her colleagues identified a hospital in which full data on admissions were available from 1956 to 1997. The results demonstrate that the increase for African Americans under age 50 years has been progressive from 1970 onwards and is greater than 20-fold on a population at-risk basis or compared with hospital admissions. The timing of the changes and the consistency of the increase challenges many hypotheses about the causes of the increase in asthma.

Download references

Author information

Authors and Affiliations

  1. Asthma and Allergic Diseases Center, University of Virginia, PO Box 801355, 22908, Charlottesville, VA, USA

    Thomas A. E. Platts-Mills MD, PhD

Authors
  1. Thomas A. E. Platts-Mills MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Platts-Mills, T.A.E. The role of allergens in the induction of asthma. Curr Allergy Asthma Rep 2, 175–180 (2002). https://doi.org/10.1007/s11882-002-0013-2

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11882-002-0013-2

Keywords

Search

Navigation