Anaphylaxis, Peanut Allergy
& Helminthic Therapy

Evidence for the use of the immunotherapy helminthic therapy to treat Anaphylaxis and Peanut Allergy

Recent research clearly shows that anaphylaxis as a result of food (peanut) allergy can be both prevented and stopped by helminthic infection.

Anaphylaxis can occur by two mechanisms, the first and most serious with regard to peanut allergy is IgE dependent. This excellent paper by Bashir et al (M. E. H. Bashir, P. Anderson, I. J. Fuss, H. N. Shi and C. Nagler-Anderson. Journal of Immunology. 2002. 169, 3284-3292. (PMID: 12218148)) indicates that IgE dependent anaphylaxis could not be provoked in mice that had been inoculated with helminths.

Two years later, Managan at al (N.E Mangan, R.E. Fallon, P. Smith, N. van Rooijen, A. N. McKenzie, P. G Fallon. Journal of Immunology. 2004, 15;173(10), 6346-56. (PMID: 15528374)) clearly demonstrated that mice inoculated with helminths were protected from both IgE and IgE-independent anaphylaxis.

Both studies unequivocally demonstrate a central role for the cytokine IL-10 in preventing anaphylactic reactions, and interestingly IL-10 levels in humans increase substantially after exposure to helminths.

Paradoxically helminths provoke a marked IgE response, which play a central role in allergy, and increase in circulating levels of IgE. But in the case of allergy, there is no worsening of allergic symptoms following inoculation with helminths. This has been clearly demonstrated in humans by J. Feary and D. I. Pritchardw et al (. Feary, A. Venn, A. Brownw, D. Hooiw, F. H. Falconew, K. Mortimerz, D. I. Pritchard, J. Britton, Clinical and Experimental Allergy. 2009, 39(7):1060-8. (PMID: 19400893)). It is speculated that helminths have evolved to elicit this response to saturate IgE receptors with IgE that is non-specific to worms, and in doing so saturate receptors with IgE that are non-specific to allergens. The allergy still exists, but it appears to be blocked.

Peanut allergy accounts for the majority of all severe food allergies. The allergy commonly presents in childhood and affects between 4-8% of all children (Y.E. Stoneham et.al. Lancet. 1994, 93(2), 446-56), with 1-2% of adults effected. Most children who develop peanut allergy will remain allergic for the remainder of their lives, however a small but significant proportion become tolerant as they grow older.

Of the eight common food types responsible for the majority of food allergies, (cows milk, eggs, soy, wheat, peanuts, tree nuts, fish and shell fish), peanuts, along with fish and shellfish, are the most likely food to produce anaphylaxis, which can be fatal. However unlike fish and shell fish, peanuts are ubiquitous, being used in many food manufacturing facilities where it can be difficult to isolate the peanuts from other food preparation. Furthermore, allergic symptoms can present following ingestion of less than 2 mg of peanut protein(s) where a single peanut contains approximately 200 mg of proteins. These two observations help explain why of all causes of anaphylaxis due to food allergy, peanuts are responsible for more admissions to emergency departments in the USA than any other food type. This problem is demonstrated by the fact that 75% of those with peanut allergy are accidentally exposed to peanut containing foods or products annually, and suffer an allergic or anaphylactic reaction as a consequence.

Although many foods can cause allergic type reactions, peanuts primarily provoke a IgE dependent type I hypersensitivity reaction. The presence of peanut proteins provoke the rapid response of peanut specific IgE antibodies. These antibodies bind to mast and basophils cells resulting in the release of inflammatory compounds such as histamine. Cytokines and chemokines are also released which then signal other inflammatory cells resulting in a late phase allergic response. Approximately 20-30% of all anaphylactic reactions show this biphasic response, in which allergic symptoms reappear 1-8 hours following the initial symptoms. The onset of asthmatic type symptoms and delayed treatment with epinephrine are associated with a poor outcome. 4% of those with anaphylactic reactions to peanut exposure experience hypotension, arrhythmia, and cardiac arrest as a consequence of first reaction to exposure to peanut containing food.

Management of peanut allergy is primarily based on education, helping people and families to avoid peanuts. Highly sensitive individuals must recognise early symptoms and be able to self administer injectable epinephrine. Anti-histamines are also used as an adjunct to epinephrine. There is currently no prophylactic medications that are available for people suffering from this allergy and trials of immuno-modulatory drugs such as omalizumab which specifically binds IgE have been stopped due to side effects which can be as severe as the reaction to the peanuts.

Therefore, Helminthic therapy, deliberate infection with safe numbers of benign intestinal parasitic worms, represents the best option for treating food allergies, and peanut allergy and anaphylaxis in particular.

Hookworm and whipworm in small numbers are safe, do not cause disease, do not proliferate within the host, do not represent any practical risk of infection to others, and are easily and safely eliminated. While benefit depends upon continued hosting of the helminths, and the risk of unknown loss of helminths and the return of anaphylaxis accompanied by a relaxation of vigilance and avoidance of peanuts is problematic, it is easy to test for continued hosting of helminths.


Helminthic Therapy & Food Allergies, with an emphasis on Peanut allergy and Anaphylaxis: Science

For a copy of the full text of any papers here, and many others, please contact us being sure to name the disease, or subject, you would like the papers to investigate.


Helminth Infection Protects Mice from Anaphylaxis via IL-10-Producing B Cells

Abstract

Modulation of the immune system by infection with helminth parasites, including schistosomes, is proposed to reduce the levels of allergic responses in infected individuals. In this study we investigated whether experimental infection with Schistosoma man- soni could alter the susceptibility of mice to an extreme allergic response, anaphylaxis. We formally demonstrate that S. mansoni infection protects mice from a experimental model of systemic fatal anaphylaxis. The worm stage of infection is shown to mediate this protective effect. In vivo depletion studies demonstrated an imperative role for B cells and IL-10 in worm-mediated protection. Furthermore, worm infection of mice increases the frequency of IL-10-producing B cells compared with that in uninfected mice. However, transfer of B cells from worm-infected mice or in vitro worm-modulated B cell to sensitized recipients exacerbated anaphylaxis, which was attributed to the presence of elevated levels of IL-4-producing B cells. Worm-modulated, IL-10-producing B cells from IL-4-deficient, but not IL-5-, IL-9- or IL-13-deficient, mice conferred complete resistance to anaphylaxis when transferred to naive mice. Therefore, we have dissected a novel immunomodulatory mechanism induced by S. mansoni worms that is dependent on an IL-10-producing B cell population that can protect against allergic hypersensitivity. These data support a role for helminth immune modulation in the hygiene hypothesis and further illustrate the delicate balance between parasite induction of protective regulatory (IL-10) responses and detrimental (IL-4) allergic responses. The Journal of Immunology, 2004, 173: 6346 6356.


An Enteric Helminth Infection Protects Against an Allergic Response to Dietary Antigen

Abstract

Although helminths induce a polarized Th2 response they have been shown, in clinical studies, to confer protection against allergies. To elucidate the basis for this paradox, we have examined the influence of an enteric helminth infection on a model of food allergy. Upon Ag challenge, mice fed peanut (PN) extract plus the mucosal adjuvant cholera toxin (CT) produced PN-specific IgE that correlated with systemic anaphylactic symptoms and elevated plasma histamine. PN-specific IgE was not induced in helminth-infected mice fed PN without CT. Moreover, when PN plus CT was fed to helminth-infected mice, both PN-specific IgE and anaphylactic symptoms were greatly diminished. The down-regulation of PN-specific IgE was associated with a marked reduction in the secretion of IL-13 by PN-specific T cells. When helminth-infected PN plus CT-sensitized mice were treated with neutralizing Abs to IL-10, the PN-specific IgE response and anaphylactic symptoms were similar to, or greater than, those seen in mice that receive PN and CT alone. Taken together, these results suggest that helminth-dependent protection against allergic disease involves immunoregulatory mechanisms that block production of allergen-specific IgE. The Journal of Immunology, 2002, 169: 32843292. PMID: 12218148


Enteric infection acts as an adjuvant for the response to a model food antigen.

Abstract

Although helminths induce a polarized Th2 response they have been shown, in clinical studies, to confer protection against allergies. To elucidate the basis for this paradox, we have examined the influence of an enteric helminth infection on a model of food allergy. Upon Ag challenge, mice fed peanut (PN) extract plus the mucosal adjuvant cholera toxin (CT) produced PN-specific IgE that correlated with systemic anaphylactic symptoms and elevated plasma histamine. PN-specific IgE was not induced in helminth-infected mice fed PN without CT. Moreover, when PN plus CT was fed to helminth-infected mice, both PN-specific IgE and anaphylactic symptoms were greatly diminished. The down-regulation of PN-specific IgE was associated with a marked reduction in the secretion of IL-13 by PN-specific T cells. When helminth-infected PN plus CT-sensitized mice were treated with neutralizing Abs to IL-10, the PN-specific IgE response and anaphylactic symptoms were similar to, or greater than, those seen in mice that receive PN and CT alone. Taken together, these results suggest that helminth-dependent protection against allergic disease involves immunoregulatory mechanisms that block production of allergen-specific IgE. The Journal of Immunology, 2002, 169: 3284 3292. PMID: 12218148


Other References

(1) Turton, J.A. (1976) IgE, parasites, and allergy. The Lancet ii:686 (text not available online, too old)

(2) Inoculating Celiac Disease Patients With the Human Hookworm Necator Americanus: Evaluating Immunity and Gluten-Sensitivity

(3) Strachan, D. P. 1989. Hay fever, hygiene and household size. (The Hygiene Hypothesis) Br. Med. J. 299: 1259.

(4) Cookson, W. O. C. M., and M. F. Moffatt. 1997. Asthma: an epidemic-in-the-absence-of infection? Science 275:41.

(5) Mao, X.-Q., D.-J. Sun, A. Miyoshi, Z. Feng, Z. T. Handzel, J. M. Hopkin, and T. Shirakawa. 2000. The link between helminthic infection and atopy (allergy, asthma, eczema). Parasitol. Today 16:186.

(6) Weiss, S. T. 2000. Parasites and asthma/allergy: what is the relationship? J. Allergy Clin. Immunol. 105:205.

(7) Wills-Karp, M., J. Santeliz, and C. L. Karp. 2001. The germless theory of allergic disease: revisiting the hygiene hypothesis. Nat. Rev. Immunol. 1:69.

(8) Yazdanbakhsh, M., A. van den Biggelaar, and R. M. Maizels. 2001. Th2 responses without atopy: immunoregulation in chronic helminth infections and reduced allergic disease. Trends Immunol. 22:372.

(9) Yazdanbakhsh, M., P. G. Kremsner, and R. van Ree. 2002. Allergy, parasites and the hygiene hypothesis. Science 296:490.