Keven J. Turner

The association between Dermatophagoides mites and the increasing prevalence of asthma in village communities within the Papua New Guinea highlands

The prevalence of asthma among adults but not children living in eight South Fore villages of the Eastern Highlands of Papua New Guinea has risen dramatically over the past decade and now is 6 per 1000 in the age group less than 20 yr and 73 per 1000 in the age group more than 20 yr. Allergy to house dust mites appears to be a significant feature in the disease pathogenesis, and it is likely that this is associated with modifications to traditional lifestyles by the recent introduction of blankets and changes in sleeping habits that promote a more fertile environment for growth and multiplication of mites. Asthma is now provoked by a wide range of factors such as exertion, stress, and antecedent respiratory tract infections, which have always been common features of the South Fore way of life. This suggests that allergic reactivity may be the precursor of bronchial hyperreactivity that, once manifested, can be triggered by a variety of stimuli, not all of which are immunologic in origin.

Non-Specific Potentiation of IgE by Parasitic Infections in Man

Infection with the helminthic parasites Ascaris lumbricoides and/or Necator americanus (hookworm) induces the production in man of high levels of serum IgE. The specificity of this IgE antibody when measured by RAST to a wide range of allergens was restricted in general to the helminthic antigens. Absorption of the sera with immunosorbents produced by coupling extracts of A. lumbricoides to CNBr activated Sepharose 4B established that Ascaris antigen specific IgE antibodies contributed a minor fraction of the total serum IgE. These observations suggest that parasitic infections in man as in laboratory animals potentiate the production of high levels of IgE with specificity unrelated to that of the parasite antigens. While the specificity of this potentiated IgE was not established, it is not directed towards inhalant allergens.

Relationship between mite densities and the prevalence of asthma: comparative studies in two populations in the Eastern Highlands of Papua New Guinea

The recent dramatic rise from 0.1 to 7.3% in the prevalence of adult asthma in the South Fore area of the Eastern Highlands of Papua New Guinea (PNG) has not been matched by a similar increase in asthma in the adjacent Asaro valley, where the prevalence remains extremely low at 0.3%. While the living conditions of these two populations appear comparable, the mean density of house dust mite (principally Dermatophagoides pteronyssinus) in blankets of residents in the Asaro valley was found to be significantly lower (283/g dust) than that of a corresponding random selection in the South Fore (1371/g dust). Since from 200 to 600 mites per g dust have been reported to constitute a risk factor for asthma, the data suggest that the relative risk for asthma in the Asaro valley population is low compared with that in the South Fore. In randomly selected sera, both IgE and IgG antibodies to D. pteronyssinus from the Asaro valley were comparable with those of a group of non‐asthmatics from the South Fore (mean 4.39 vs 3.43 U/ml for IgE antibodies and 1832 vs 1815 U/ml for IgG antibodies for Asaro valley vs South Fore, respectively) but significantly lower (P < 0.001) than corresponding data for subjects in the South Fore with asthma (108.6 U/ml and 3365 U/ml, respectively). This study emphasizes the interplay between genetic and environmental factors in determining the development of asthma, and highlights the importance of house dust mites in the pathogenesis of asthma in the Eastern Highlands of Papua New Guinea.

Studies on bronchial hyperreactivity, allergic responsiveness, and asthma in rural and urban children of the highlands of Papua New Guinea

The prevalence of asthma and allergic responsiveness in rural and urban children of the highlands of Papua New Guinea was studied. Bronchial provocation studies with histamine demonstrated significant bronchial hyperreactivity in 0.5% (1 in 195) rural and 1.7% (1 in 59) urban children, rates which were significantly lower than those observed in corresponding adult populations (7%). Urban children demonstrated a higher incidence of skin test reactivity toward Dermatophagoides pteronyssinus, Aspergillus fumigatus, and dog dander than did the rural children. However, there were no significant differences between these populations with regard to total serum IgE levels, the degree of parasitism as judged by stool examination, or allergic responses to Ascaris suum, plantain, and coffee bean husk. A more detailed study demonstrated age- and sex-related differences in total IgE and mite-specific RAST scores in the rural but not the urban population. These data suggest an active suppression of the capacity of children to mount an IgE response to environmental allergens such as the mite manifesting itself as low asthma prevalence. The data also indicate that, although the underlying defect of bronchial hyperreactivity in asthma may be genetically inherited, it is not revealed until the lung has received an allergen-induced inflammatory insult.

Prevalence and Familial Association of Atopic Disease and its Relationship to Serum IgE Levels in 1,061 School Children and Their Families

The prevalence of asthma, hay fever, wheezing bronchitis, and eczema was found to be independent of age and sex in 1,598 school children aged 6–17 years who were resident in Busselton, Western Australia. Prevalence studies show that both asthma and hay fever are inherited diseases but that the mode of inheritance differs, since there is evidence in hay fever but not asthma of a cumulative effect resulting from both parents expressing the disease. The serum IgE levels of children with all categories of allergic disease reported in this study were significantly elevated above those of control children of similar age. The mother’s serum IgE concetration was more closely related to that of her son than to that of her daughter. The converse relationship existed for girls. These findings are interpreted on the basis that the X-chromosome of man carries genes which influence IgE synthesis.

Enumeration of human immunoglobulin-secreting cells by the ELISA-plaque method: IgE and IgG isotypes.

A new system is described for the enumeration of human immunoglobulin-secreting cells (ISC), based upon the ELISA methodology. In principle, putative ISC are incubated over a solid phase containing bound anti-Ig of the isotype being tested. Secreted Ig is immobilized at or near the point of release from the ISC, and the resulting Ig fingerprint of the ISC is then visualized by the sequential application of an anti-Ig-alkaline phosphatase conjugate, followed by a substrate-agarose overlay. The system is capable of detecting IgE-secreting cells, and pokeweed mitogen-stimulated IgG-secreting cells with sensitivity at least equivalent to the protein A hemolytic plaque assay.

Prevalence of Asthma in the South Fore People of the Okapa District of Papua New Guinea

The prevalence of asthma in a population of the South Fore linguistic group of the Eastern Highlands Province of Papua New Guinea has shown a remarkable increase in the last decade and is now 7.3% in adults and 0.6% in children. Allergy to house dust mite appears to play a major role in the disease pathogenesis. The low childhood prevalence may be associated with endemic parasitism which operates by suppressing production of IgE antibodies to ubiquitous allergens. This suppression is significantly correlated with age in boys of 6-20 years, but not for girls who retain low serum titres throughout the entire age range. Bronchial reactivity, assessed by histamine inhalation test, does not identify asymptomatic children who may be potential asthmatic subjects suggesting that, in this population, bronchial hyperreactivity follows the development of immunological hypersensitivity.

Prevalence and features of asthma in a sample survey of urban Goroka, Papua New Guinea

This study found a prevalence of asthma of 2.5% in adults and 0.2% in children in Goroka, the major town and administrative centre of the Eastern Highlands Province of Papua New Guinea. The disease features are similar to those found in previous studies in Papua New Guinea: late age of onset and virtual absence of childhood cases; strong association with allergy to house dust mite and high mite‐specific IgE levels; and considerable impairment of resting lung function. However, the prevalence is much lower than that recently found in the nearby rural South Fore linguistic group of the Okapa District. Moreover, it was noted that a preponderance of the urban cases in the present study were originally from Okapa. The implication is that particular local tetiological factors may be responsible for the documented rise in prevalence in the South Fore (Okapa) people, rather than the process of ‘Westernization’per se. This creates a valuable opportunity to learn more about the pathogenesis of asthma.

In vitro Synthesis of IgE by Human Peripheral Blood Leucocytes

The assessment of IgE production in cultures of T- and B-cells from peripheral blood is proving a useful tool to probe IgE immunoregulation in human atopics. The present study contrasts secretion and synthesis as indices of IgE production, and demonstrates that these measures yield comparable data upon the magnitude and direction of regulatory T-cell effects (help vs. suppression) in severe atopics. The majority of peripheral blood B-cell samples from the atopics in this study exhibited spontaneous IgE synthesis and secretion, and in vitro T-cell help and suppression were observed with equal frequency within the sample population. Repeated testing of individual atopics indicated that the direction of T-cell effects remained stable in some (but not all) atopics over periods as long as 3 years.

In vivo Arming of Cutaneous Mast Cell Receptors by IgE Released from Macrophages

Intracutaneous injection of purified peritoneal macrophages harvested from ovalbumin (OVA)-hypersensitive high-IgE-responder BN rats into naive animals sensitised the injection sites for subsequent OVA-specific passive cutaneous anaphylaxis (PCA) reactions. The underlying mechanism(s) were investigated using a macrophage cell line (WEHI 265.1), which exhibited comparable sensitising activity in rat or mouse skin, after initial pulsing in vitro with antiserum rich in OVA-specific IgE. Transfer of OVA-hypersensitivity by the cell line (1) was IgE-dependent and did not occur when the cells were pre-exposed to antiserum containing OVA-specific IgG alone, (2) was blockable by saturation of cell surface receptors in the recipient with myeloma IgE (but not myeloma IgG), and (3) did not occur in mast cell-deficient mice carrying the W/Wv mutation, in contrast to their normal heterozygous littermates which developed marked OVA-hypersensitivity at the injection site. These results are consistent with arming of IgE-receptors on cutaneous mast cells by IgE antibody released from macrophages, and hint at a possible role for phagocytes in amplifying IgE-mediated reactions in tissues.