Immunoglobulin E and allergic disease in Africa

Although the prevalence of allergic disease appears to be increasing in most parts of the world [1±3], there are still important differences in the prevalence and pattern of disease both between and within developed and developing countries [4]. Studies in Africa, for example, have found a generally lower prevalence of self-reported asthma symptoms [4±6] exercise-induced bronchospasm [7], and allergic rhinoconjunctivitis [6] relative to the developed world, especially in rural compared with urban areas [5,8±10]. In addition to this generally lower prevalence of allergic disease, immunoglobulin (Ig) E levels in African populations tend to be high [11±15], and levels in nonasthmatics tend to be higher than in asthmatics. Since asthma, bronchial hyperreactivity and allergic disease tend to be associated with high IgE levels in the developed world [16±18], this apparent paradox calls for a reappraisal of the role of IgE in allergy in these populations. One hypothesis is that the high levels of IgE in African populations are caused by parasitic infestation, and that this in turn somehow reduces the risk of allergic disease. In this issue of Clinical and Experimental Allergy, Selassie et al. provide some new evidence relating to this hypothesis [19]. Intestinal parasites are potent stimulators of both parasitespeci®c IgE, which is important in the host immune response to parasite [20,21], and polyclonal or non-speci®c IgE. Parasite speci®c IgE attaches to high-af®nity Fc receptors on mast cells, and neighbouring speci®c immunoglobulins cross-link and trigger mast cell degranulation. This process mediates an antiparasite response via the release of pro-in ̄ammatory cytokines. The same mechanism is involved in the pathogenesis of asthma and other allergic disease in which immune responses are triggered by allergen-speci®c IgE [17]. Since the immune responses involved in dealing with both parasites and allergy appear to be similar, it is plausible that parasitosis and allergy are somehow interrelated. The nature of this relationship has been extensively reviewed [22±24] but is still not understood. From experimental data [23,25] it has been postulated that saturation of IgE receptors by the Fc fragment of parasiteinduced non-speci®c IgE will block the cross-linking of allergen-speci®c IgE on the surface of mast cells and therefore prevent their degranulation and the subsequent allergic response. Thus parasite infestation may protect against allergy whilst, by the same token, the parasitekilling response is likely to be similarly inhibited. It has been postulated that the ability to generate this polyclonal response has evolved in the parasite because it helps to evade host immunity [24]. This latter theory is supported by work in Ascaris-endemic areas of Venezuela where Hagel et al. found that high total IgE was a marker of increased risk of re-infection after anthelmintic treatment [21]. Other studies have reached similar conclusions [20,26]. This hypothesis, that current parasitic infection can protect against development and exacerbation of allergic disease, has been proposed to explain much of the available epidemiological evidence, but has not yet been de®nitively explored. Some studies provide evidence in support of this hypothesis, including a descriptive study of asthma in Kenya [27] which found that only 9% of stools from asthmatic patients showed parasite infestation compared with 26% of a control group. Unusual evidence was also reported by Turton [28], who found that his hay fever improved markedly after three separate self-infections with hookworm (Necator americanus). He also demonstrated that his speci®c antiparasite IgE level increased threefold during the 13-month period in which the infections occurred, but his total IgE did not increase in relation to preinfection levels. These ®ndings, though based on the experience of a single individual, suggest that parasite-speci®c IgE was blocking the allergic response. Further evidence comes from surveys in The Gambia [12] and Rhodesia [11], which both found higher levels of IgE in rural areas, in association with lower rates of asthma. They attributed the differences in IgE levels to differences in parasitosis in the rural areas, but did not determine whether these subjects were carrying intestinal parasites. The importance of this omission is demonstrated by a study in Nigeria where lower levels of IgE were observed in asthmatics, but with no difference in stool parasite counts between cases and controls [13]. Similar ®ndings in Tanzanian school-children [14] also do not support the parasite-protective hypothesis. There is rather more evidence that parasitic infestation, as opposed to protecting against allergic disease, actually increases the risk. Lynch and colleagues [29] studied asthmatic children in Venezuelan slums and found that their asthma control improved signi®cantly after anthelmintic treatment. Dold et al. studied school children from the former East and West Germany [30], looking at clinical evidence of allergic disease and immunological markers of parasitic infection. In a longitudinal study, in which a cohort of children was surveyed twice 3 years apart, they observed an increase in the prevalence of allergic rhinitis in children who became seropositive to Ascaris IgE. They also found a higher frequency of allergen-speci®c IgE in those who were Ascaris-seropositive at either survey, and that a positive Ascaris IgE result was a stronger risk factor for allergic