Immunological peculiarities in a "traditional" worm infested Papua New Guinean society and possible implications for the increase of allergies in fast changing "modern" societies

Abstract

The objective of this study is to describe the peculiarities of allergic sensitization in a Papua New Guinean society largely following a traditional lifestyle and to develop a theory explaining the increase of allergies in "modern" industrialized societies. At the beginning, we intend to give a coherent introduction to the pathophysiology of allergic reactions, particularly to the immunoglobulin E (IgE) composition, a crucial characteristic of the IgE system. Subsequently mites are identified as the clinically most relevant allergen source on Karkar Island. We confirmed the association of worm infestation and highly elevated total IgE levels. Moreover a significant positive correlation of total IgE and specific IgE (in-vitro sensitisation measured by RAST) was shown. Thus we deduce that the entire IgE system is triggered by helminth infections i.e. not only total IgE (contested allergy protective variable) but also allergen specific IgE (undisputed allergy mediating variable). Interestingly, triggering the allergy mediating part of the IgE system (specific IgE) dos not seem to lead to an increased prevalence of positive skin prick test (SPT) reactivity or allergy on Karkar as we have previously found that only 4.4% of the islanders suffer from allergic rhinoconjunctivitis/asthma (atopic dermatitis was absent). The worm induced elevated total IgE levels appear to protect the islanders from allergic reactions and may explain the striking epidemiological discrepancy between high in-vitro (RAST) and low in-vivo (SPT) sensitisation. We were able to show a significant protective effect of a low ratio of specific IgE to total IgE (i.e. a low allergen specific activity): The prevalence of positive skin prick test reactions upon contact with house dust mite extracts was significantly reduced when mite specific activity was lower than 0.1%. The pattern of sensitization on Karkar is an image/picture/reflection of the allergens existing in the island`s environment - irrespective of the allergological potency of the different allergens. The assumed "general/twofold IgE boost" in worm infested individuals seems to have two consequences: firstly we see the already described dissociation of RAST and SPT/allergy. Secondly it is possible that the IgE boost reveals a pre-existing clinically and serologically invisible (not measurable) "low level" immunological sensitization against multiple environmental antigens. Pushing levels of allergic sensitisation over the detection limit, worms may act like a magnifying glass which shows us that the immune system generally controls/samples a much larger array of antigens than previously thought - including many allergologically "unsuspicious" substances. Based on the hypothesis that there exists the same basically universal "subliminal" immunological "screening" of innumerable environmental substances in Western countries (just serologically invisible due to the lack of worm boosts), we developed our "change hypothesis of allergogenesis": In a "modern environment" with immensely accelerated change resulting in largely increased antigen diversity there is much more possibility for cross-reactivity than in a "traditional" society. Recent studies show that even low concentration/affinity cross-reactive IgE can induce considerable histamine release/clinical reactivity. Thus the rise of allergies in industrialized societies may be a consequence of generally increased specific activities (disappearance of parasitism) and increased cross-reactivity ("confusion" of the immune system).