Int. Archs Allergy appl. Immun. 49: 814-830 (1975)
Effects of Allergy, Intestinal Helminthic Infestation and Sex on Serum IgE Concentrations and Immediate Skin Hypersensitivity in Three Ethnic Groups A nn O rren and E ugene B. D owdle Department of Clinical Science and Immunology, University of Cape Town, Cape Town
Abstract. Serum IgE concentrations were measured in 232 blood donors resi dent in the Western Cape, South Africa. Subjects were interviewed for histories of allergy and skin tested with a variety of common allergens. Faecal specimens were collected for microscopic examination. Results confirmed that Cape Coloureds and Africans tend to have elevated serum IgE concentrations and showed that African males have a high prevalence of immediate skin hypersensitivity. Cape Coloureds and Africans had high prevalences of helminthic infestation and relatively low prevalence of allergic symptoms. Only in Whites were elevated serum IgE concen trations associated with positive allergic histories; in this group, results suggested that the sex difference in serum IgE concentrations observed previously is owing to differences in the IgE responses of allergic males and females.
Introduction Epidemiological data assembled by this laboratory have confirmed previous reports [J ohansson et al., 1968] that serum IgE concentrations tend to be elevated in indigenous African populations, and have shown that, within the White population, there is a significant tendency for males to have higher serum IgE concentrations than females [O rren and D owdle, 1975]. The recognized associations between elevated ser um IgE concentrations, allergic disease and helminthic infestation sug gested that differences in the prevalence of these disorders might explain the population differences we observed.
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/8/2018 5:48:49 AM
Received: January 17, 1975.
Orren/D owdle
815
In order to investigate this possibility and to determine the interrela tionships between various factors that influence serum IgE concentra tions, we have undertaken a more detailed epidemiological survey of resi dents of the Western Cape Province of South Africa representing the three local ethnic groups. In this study serum IgE concentrations were measured and the data obtained analyzed with respect to race, sex, al lergic status, and evidence of helminthic infestation. The results of this survey form the basis of this report.
Materials and Methods Subjects The population sample studied was drawn from a panel of adult blood donors and was comprised of individuals belonging to the three ethnic groups living in the Western Cape. These groups have been described in a previous report [Orren and D owdle, 1975]; briefly they were (i) the Whites, (ii) the Cape Coloureds who have arisen due to interbreeding of While, Southern African (Bushman and H ot tentot) and Asian peoples, and (iii) the Africans, most of whom belonged to the Xhosa tribe. Relatively few African females donated blood, with the result that we were only able to interview nine subjects in that group. The survey was conducted during the months October to February. It is during this period that seasonal allergic symptoms occur most commonly in South Africa. A total of 283 individuals were interviewed; 268 had skin tests performed, 232 had their serum IgE concentrations determined and 226 had their stools examined. Since there were some subjects in whom testing was incomplete, the numbers available for the analyses were generally slightly lower.
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/8/2018 5:48:49 AM
Histories o f Allergic Symptoms Subjects who participated in the survey were questioned, by an experienced in terviewer, for a prescribed list of symptoms of allergy. In deciding whether or not symptoms could be ascribed to immediate hypersensitivity, reliance was placed pri marily upon assessment of the nature of the symptoms and their congruence with generally accepted clinical description. In addition, such factors as seasonal exac erbation and relief from anti-histaminic drugs or disodium cromoglycate were tak en into account. On the basis of the extent to which symptoms caused social, economic or phys ical disability, or the extent to which they obtruded into the daily life of the indi vidual, subjects were graded as being non-allergic, mildly allergic, or clinically al lergic. Although seemingly arbitrary, this distinction could, in most cases, be made relatively easily. Thus, subjects who denied relevant systems were classed as nonallergic, while those who admitted, on direct questioning, to occasional symptoms which caused minimal inconvenience were classified as mildly allergic. Those sub jects who had required or sought medical advice for their symptoms, who took
816
Orren/D owdle
pains to avoid provocative stimuli, or who were acutely conscious of their symp toms, were classified as clinically allergic. Being blood donors, the subjects were generally in good health. Thus subjects who were classified as ‘clinically allergic’ would probably have been regarded as having mild symptoms in the usual clinical context. For some of the statistical tests we found it necessary to group together all subjects with symptoms of allergy in an ‘allergic’ group. It should be recognized that the diagnosis of allergy and the assessment of its severity rested largely upon the interpretation by the clinician of the patient’s own account of his or her symptoms. There were few, if any, objective criteria which could be relied upon in cases of doubt. Syndromes such as vernal conjunctivitis, allergic rhinitis and childhood asthma with eczema were usually typical and could be ascribed to allergy without much uncertainty; on the other hand, in conditions such as ‘food allergy’, urticaria, migraine, anaphylaxis, and contact dermatitis, the clinical picture was often vague and the pathogenetic role of the IgE-mediated type I hypersensitivity reaction is uncertain. The assignment of these cases to one or other category depended on the judgement of the physician. In all instances we assigned cases without prior knowledge of the skin test result or serum IgE con centration. A further problem was encountered in the case of many of the African and some of the Cape Coloured subjects. This arose largely from difficulties in com munication that were not entirely due to difficulties with language. In many inst ances we were left with the impression that their cultural background and social circumstances so modified their awareness of, or reaction to, minor symptoms that they did not complain of them or admit to their presence. The prevalence of aller gy in these subjects, therefore, may have been underestimated by the interview we conducted. One stool sample was collected from each individual and a wet specimen was examined microscopically for the presence of parasites or ova. Skin Tests for Immediate Cutaneous Hypersensitivity to Common Allergens Subjects were tested on the anterior surface of a forearm by the conventional prick test method. Test solutions included extracts of 16 common inhalant aller gens, an Ascaris extract and a control solution (Bencard, Brentford, England) (ta ble III). None of the subjects were taking anti-histamine drugs at the time of the study. Subjects were considered skin test positive if they reacted with a wheal greater than 2 mm or a flare greater than 4 mm to any of the allergen solutions. The slight trauma of a carefully performed prick test causes no reaction [Pepys, 1971], and small reactions are as indicative of the presence of skin-sensitizing anti body as large ones. Seven of the 268 subjects who were tested had small positive reactions to the control solution; as they all had considerably larger reactions to at least one other solution we classed them as skin test positive.
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/8/2018 5:48:49 AM
IgE Determinations These were performed using the radio-radial-immunodiffusion method devel oped by Rowe [1969], modified so that the lower limit of sensitivity was 25 U/ml. The method has previously been described in detail [Orren and D owdle, 1975].
Serum IgE Concentrations
817
Statistical Tests Distribution-free, nonparamctric statistical procedures were used to analyze the results. Where appropriate, the chi-square and the Kruskal-Wallis one-way analysis of variance were used [Siegel, 1956], When small number of subjects in certain ca tegories precluded the use of these tests, the Fisher exact probability test or the Mann-Whitney U test were used. Whenever used in this paper, the term ‘signifi cant’ refers to values of p
Effects of Allergy, Intestinal Helminthic Infestation and Sex on Serum IgE Concentrations and Immediate Skin Hypersensitivity in Three Ethnic Groups A nn O rren and E ugene B. D owdle Department of Clinical Science and Immunology, University of Cape Town, Cape Town
Abstract. Serum IgE concentrations were measured in 232 blood donors resi dent in the Western Cape, South Africa. Subjects were interviewed for histories of allergy and skin tested with a variety of common allergens. Faecal specimens were collected for microscopic examination. Results confirmed that Cape Coloureds and Africans tend to have elevated serum IgE concentrations and showed that African males have a high prevalence of immediate skin hypersensitivity. Cape Coloureds and Africans had high prevalences of helminthic infestation and relatively low prevalence of allergic symptoms. Only in Whites were elevated serum IgE concen trations associated with positive allergic histories; in this group, results suggested that the sex difference in serum IgE concentrations observed previously is owing to differences in the IgE responses of allergic males and females.
Introduction Epidemiological data assembled by this laboratory have confirmed previous reports [J ohansson et al., 1968] that serum IgE concentrations tend to be elevated in indigenous African populations, and have shown that, within the White population, there is a significant tendency for males to have higher serum IgE concentrations than females [O rren and D owdle, 1975]. The recognized associations between elevated ser um IgE concentrations, allergic disease and helminthic infestation sug gested that differences in the prevalence of these disorders might explain the population differences we observed.
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/8/2018 5:48:49 AM
Received: January 17, 1975.
Orren/D owdle
815
In order to investigate this possibility and to determine the interrela tionships between various factors that influence serum IgE concentra tions, we have undertaken a more detailed epidemiological survey of resi dents of the Western Cape Province of South Africa representing the three local ethnic groups. In this study serum IgE concentrations were measured and the data obtained analyzed with respect to race, sex, al lergic status, and evidence of helminthic infestation. The results of this survey form the basis of this report.
Materials and Methods Subjects The population sample studied was drawn from a panel of adult blood donors and was comprised of individuals belonging to the three ethnic groups living in the Western Cape. These groups have been described in a previous report [Orren and D owdle, 1975]; briefly they were (i) the Whites, (ii) the Cape Coloureds who have arisen due to interbreeding of While, Southern African (Bushman and H ot tentot) and Asian peoples, and (iii) the Africans, most of whom belonged to the Xhosa tribe. Relatively few African females donated blood, with the result that we were only able to interview nine subjects in that group. The survey was conducted during the months October to February. It is during this period that seasonal allergic symptoms occur most commonly in South Africa. A total of 283 individuals were interviewed; 268 had skin tests performed, 232 had their serum IgE concentrations determined and 226 had their stools examined. Since there were some subjects in whom testing was incomplete, the numbers available for the analyses were generally slightly lower.
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/8/2018 5:48:49 AM
Histories o f Allergic Symptoms Subjects who participated in the survey were questioned, by an experienced in terviewer, for a prescribed list of symptoms of allergy. In deciding whether or not symptoms could be ascribed to immediate hypersensitivity, reliance was placed pri marily upon assessment of the nature of the symptoms and their congruence with generally accepted clinical description. In addition, such factors as seasonal exac erbation and relief from anti-histaminic drugs or disodium cromoglycate were tak en into account. On the basis of the extent to which symptoms caused social, economic or phys ical disability, or the extent to which they obtruded into the daily life of the indi vidual, subjects were graded as being non-allergic, mildly allergic, or clinically al lergic. Although seemingly arbitrary, this distinction could, in most cases, be made relatively easily. Thus, subjects who denied relevant systems were classed as nonallergic, while those who admitted, on direct questioning, to occasional symptoms which caused minimal inconvenience were classified as mildly allergic. Those sub jects who had required or sought medical advice for their symptoms, who took
816
Orren/D owdle
pains to avoid provocative stimuli, or who were acutely conscious of their symp toms, were classified as clinically allergic. Being blood donors, the subjects were generally in good health. Thus subjects who were classified as ‘clinically allergic’ would probably have been regarded as having mild symptoms in the usual clinical context. For some of the statistical tests we found it necessary to group together all subjects with symptoms of allergy in an ‘allergic’ group. It should be recognized that the diagnosis of allergy and the assessment of its severity rested largely upon the interpretation by the clinician of the patient’s own account of his or her symptoms. There were few, if any, objective criteria which could be relied upon in cases of doubt. Syndromes such as vernal conjunctivitis, allergic rhinitis and childhood asthma with eczema were usually typical and could be ascribed to allergy without much uncertainty; on the other hand, in conditions such as ‘food allergy’, urticaria, migraine, anaphylaxis, and contact dermatitis, the clinical picture was often vague and the pathogenetic role of the IgE-mediated type I hypersensitivity reaction is uncertain. The assignment of these cases to one or other category depended on the judgement of the physician. In all instances we assigned cases without prior knowledge of the skin test result or serum IgE con centration. A further problem was encountered in the case of many of the African and some of the Cape Coloured subjects. This arose largely from difficulties in com munication that were not entirely due to difficulties with language. In many inst ances we were left with the impression that their cultural background and social circumstances so modified their awareness of, or reaction to, minor symptoms that they did not complain of them or admit to their presence. The prevalence of aller gy in these subjects, therefore, may have been underestimated by the interview we conducted. One stool sample was collected from each individual and a wet specimen was examined microscopically for the presence of parasites or ova. Skin Tests for Immediate Cutaneous Hypersensitivity to Common Allergens Subjects were tested on the anterior surface of a forearm by the conventional prick test method. Test solutions included extracts of 16 common inhalant aller gens, an Ascaris extract and a control solution (Bencard, Brentford, England) (ta ble III). None of the subjects were taking anti-histamine drugs at the time of the study. Subjects were considered skin test positive if they reacted with a wheal greater than 2 mm or a flare greater than 4 mm to any of the allergen solutions. The slight trauma of a carefully performed prick test causes no reaction [Pepys, 1971], and small reactions are as indicative of the presence of skin-sensitizing anti body as large ones. Seven of the 268 subjects who were tested had small positive reactions to the control solution; as they all had considerably larger reactions to at least one other solution we classed them as skin test positive.
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/8/2018 5:48:49 AM
IgE Determinations These were performed using the radio-radial-immunodiffusion method devel oped by Rowe [1969], modified so that the lower limit of sensitivity was 25 U/ml. The method has previously been described in detail [Orren and D owdle, 1975].
Serum IgE Concentrations
817
Statistical Tests Distribution-free, nonparamctric statistical procedures were used to analyze the results. Where appropriate, the chi-square and the Kruskal-Wallis one-way analysis of variance were used [Siegel, 1956], When small number of subjects in certain ca tegories precluded the use of these tests, the Fisher exact probability test or the Mann-Whitney U test were used. Whenever used in this paper, the term ‘signifi cant’ refers to values of p
