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Parasite infections and the risk of asthma and atopy
  1. Instituto de Biomedicina
  2. Central University of Venezuela
  3. Caracas
  4. Venezuela
  5. Department of Paediatrics
  6. University of Western Australia
  7. GPO Box D184
  8. Perth 6001
  9. Australia

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Common environmental allergens stimulate IgE responses and produce allergic disease, but the allergens that produce the most potent IgE responses in nature originate from helminthic parasites.1 ,2 Since parasitic infection is endemic in the majority of the world’s population, the relationship between helminthic infection and the IgE response is highly relevant to the understanding of allergic diseases. There is a general consensus that IgE antibody is an important component of the immune resistance to helminthiasis,5-9 although some conflicting results have been obtained.3 ,4 Local IgE reactions can create unfavourable conditions in the gut for intestinal parasites, and IgE can mediate the cytotoxic activity of eosinophils against parasitic larvae. These observations have led to the concept that, from an evolutionary perspective, the primary function of the allergic response may be as part of an anti-parasitic protective mechanism, and allergic disease may be the undesirable reaction towards otherwise inoffensive environmental substances.10 In developed countries the prevalence of allergic disease has increased over recent years at the same time that improved sanitary conditions have caused the virtual elimination of parasites.11-13 This increase in allergic diseases has recently been attributed to a Th1/Th2 imbalance caused by diminishing exposure to common bacterial and viral infections,14 ,15 but the decrease in helminthic infections should also be considered in this context.

Insight into this situation has come from recent immunological studies which have demonstrated that there are two different IgE responses to helminthic infections. The first of these is the host’s defensive response to produce IgE specific to parasite antigens. The second response is that the host also exhibits a strong non-specific Th2/interleukin 4 dependent polyclonal synthesis of IgE16-18 which results in highly elevated total serum IgE levels in parasitised populations. This polyclonal synthesis of IgE may be the helminth’s defence mechanism against the effects of anti-parasite IgE. The polyclonal stimulus can suppress allergic responses by reducing the production of specific IgE antibody, resulting in an inverse relationship between total and specific serum IgE levels.18-20 The polyclonal IgE also saturates the IgE receptors on mast cells and blocks access to specific IgE, which further inhibits allergic reactions.12 ,13 ,18 ,20 ,21This suppressive activity may be the reason for the diminished prevalence of allergic diseases reported in some tropical populations.22-26 Of great significance is the likelihood that parasites evade the immune response by stimulating excess IgE production.27 For example, in populations endemically exposed to helminths, individuals with the highest total serum IgE levels are more quickly reinfected by the parasites after anthelmintic treatment than those with lower levels.28 In addition, atopic individuals within such populations have significantly lower total IgE levels, higher specific anti-parasite IgE concentrations, and less intense helminth infections than their non-atopic counterparts.29 These observations suggest that atopic hosts may have developed more effective specific responses against parasites through evolution,31 and that helminths, also through evolution, have countered this by developing allergens that provoke a polyclonal IgE response. Atopic individuals mount the most effective IgE responses30 and, in evolutionary terms, this might compensate for the adverse effects of allergic disease. The atopic state therefore appears to favour a specific over a polyclonal IgE response, and thus the genes that determine this may have been conserved.29 However, in the absence of environmental exposure to parasites, this is more harmful than beneficial.

Molecular genetic techniques have the potential to elucidate the inherited changes underlying these evolutionary developments.32 The approaches to resolving the inherited immunogenic processes are similar to those used to investigate the molecular genetics of asthma.33-36 These investigations are facilitated by the work done to date on asthma genetics that concentrated on IgE responses.35 ,36 The chance of finding DNA sequence variations that affect specific IgE responses should be much greater in parasitised than in asthmatic populations because the IgE responses to parasites are much more intense and genetic differences in the level of IgE responses should be maximised. Detecting the gene or genes involved in polyclonal production of IgE would also be of great interest. The potential benefits of this approach to understanding human responses to parasite infection are several and include: (1) basic mechanisms of the immune system may be elucidated; (2) those particularly susceptible to parasitic infection may be identified; (3) studying the IgE antibody system in its natural state may give insight into reasons why it apparently malfunctions to cause atopic disease; and (4) novel therapeutic interventions may become apparent. As an example of a possible therapy, understanding the mechanism of polyclonal IgE production might allow an artificial stimulus to be used in atopic individuals to produce polyclonal IgE to block IgE receptors and so minimise the effect of high levels of IgE specific to inhaled antigens.

There are therefore several reasons why research into the relationship between human IgE responses and parasitic disease might have more widespread relevance. This research is unique in having the potential simultaneously to help understand two extremely common diseases, one being one of the most common diseases in developing countries and the other one of the most common diseases in developed countries.


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