Clinical Allergy, 1974, Volume A, pages 295-300

Immunoglobin E and eosinophil levels in atopicand non-atopic populations infested with hookworm

I). I. GROVE. T. O. BURSTON and I. J. FORBES

Department of Medicine., University of Adelaide, South Australia, andPapua New Guinea Institute of Medical Research. Goroka

SummaryMeasurements of serum IgE and blood eosinophil levels were carried out on subjectsin the Eastern Highlands District of" Papua New Guinea, an area of universal hook-worm infestation. Subjects were divided into asthmatic, non-asthmatic alopic, andnormal groups on the basis of clinical features and immediate hypersensitivity reac-tions to skin prick testing with a range of allergens. Serum IgE levels and bloodeosinophils were elevated in all groups as compared with values found in temperatezones. Bolh parameters were significantly higher in the asthmatic and non-asthmaticgroups compared with the normal group. These findings are consistent with the hypo-thesis that a function ofthe IgE immune system is protection against helminth infesta-tion.

IntroductionRaised serum levels of Immunoglobulin E (IgE) were initially found in the atopic dis-orders (Johansson, 1967; Johansson et ai. 1970). Increased IgE levels were subse-quently shown in a variety of helminth infestations including Ascaris liinibrieoides,(Johansson, Mellbin & Vahlquist, 1968), To.xocara spp (Hogarth-Scott, Johansson &Bennich. 1969). TricluncUa spiralis (Rosenberg. Polmar & Whalen, 1971), Capillariaphillipincnsis (Ri)senberg et al.. 1971) Scliistosoma japonicum. Wuchenria bancroftiand hookworm (Uo, Sawada & Sato. 1972). Similarly, eosinophilia has been observedfor many years in allergies and parasitic infections.

We have reported increased resistance to hookworm infestation {Necator anieri-eanu.s) in an atopic population as assessed by faecal egg counts (Grove & Forbes,1974). It was suggested that while heightened ability to produce reaginic antibodiesmay result in the development of one of the atopic disorders, it may also carry withit increased efficiency in controlling helminth infestation. This paper reports serumIgE levels and blood eosinophii levels in atopic and non-atopic populations infestedwith hookworm.

Correspondence: Dr D. I. Grove, Department of Medicine, University of Adelaide, Queen ElizabethHospital, Woodville, South Australia, 5011.

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296 /). /. Grove, T. O. Buiston and I. J. Forbes

Subjects and methodsThe investigation was carried out in the Goroka Subdistrict ofthe Eastern HighlandsDistrict of Papua New Guinea. The location and ils inhabitants have been describedin detail elsewhere (Grove & Forbes. 1974). Hookworm infestation was universal butother intestinal belminthiasis was rare. There were no significant dillerences in inten-sity of hookworm infestation between villages.

Skin testing for immediate hypersensitivity reactions was carried out by the priclcmethod on 500 \illagers using tbe following range of allergen preparations: Dermato-phagoides farinav, Candida albicatis, A.scaris lumbricoides, Sudan Grass (Bencard.England): D. ptetotiyssinwi. Mosquito. .Altvrnaria. Cladosporimn. Pcnicilliiini. Kan-garoo Grass, Pennisetum Grass. Pig Hair, Dog Hair. Hen Feathers (CommonwealthSerum Laboratories. Australia). A subject was considered atopic if a weal of 2 mm ormore was produced by at least one allergen. It was not intended that the procedureshould be e.xhauslivc. but ibat there would be a reasonable chance of identifying alarge proportion of tbe atopic population. Ten percent ofthe villagers were identifiedas atopic on this criterion.

In addition, inputients at the Goroka Uase Hospital in whom a clinical diagnosisof asthma was made were studied. Pulmonary function tests were performed on mostpatients and demonstrated reversible airways obstruction.

Atopic and non-atopic subjects were taken in similar proportions from each ofthevillages. Ages could only be estimated, but the distribution was similar in the 3 groups:asthmatics. 38+ 10 years: atopies. 33+ 15 years and controls, 39+ 14 years.

Serum IgE levels were measured by using the radioactive single radial diffusionmethod described by Rowe (1969). The standard was from a batch of pooled bumanserum. 69/204. supplied by the World Health Organization.

Blood eosinophil levels were measured by the counting chamber method describedby Dacie (1968) using eosin-acctone diluting lluid and a Neubauer counting chamber.Venepuncture was always performed early in the morning.

ResultsBoth serum IgE levels and blood cosinopbil levels were substantially greater than thosefound in temperate zones without endemic hookworm infestation (Johansson, c/a/.,1968: Dacie. 1968).

Serum IgE levels are shown in Fig. I. There was significant elevation in the non-astbmalic atopic group when compared with non-atopic villagers (P<0-02. t test).Similarly, levels were elevated in asthmatic subjects ( / '<005. t test). Wben bothgroups were combined and compared with non-atopic villagers, there was increasedstatistical significance (P<0-005, / test). Tests of signlltcance were calculated usinglogarithmically transformed values.

Blood eosinophil levels are shown in Fig. 2. There was significant elevation in theasthmatic plus non-asthmatic alopic group wben compared with the non-atopicgroup (/'<0-05. Wilcoxon's Sum of Ranks test).

A signilicant correlation was established between serum Igt levels and bloodeosinopbil levels in botb non-atopic subjects (r = 0-3492, n = 94, / ' <0 00I) and inthe astbmatic plus non-asthmatic atopic group (r = 0 3068. n = 66. /*<0-05. Fig. 3).

DiscussionThe relationship between reaginic antibodies and protective immunity in animals is

IgE, eo.sinophils, atopy atid hookworm 297

10

10

Number , 28Geomefric mean 2 330Range 340-16,000

Non- asthmaticsatopiesNumber 51Geomefnc mean 2360Range 260-20,000

JTH

0

30 -

20 i

10 •

ConrrolsNumber 93Geometric mean 1500Range 220-11,000

rni trm nrt rm r m i

10 15 20

iqE u/ml {xlO'j

Fit;. I- Serum IgE levels in asthmatics, non-asthmatic alopics and normal subjects.

20 r

1 0 - fTTTT

20

10

Asthmatics + atopiesNumber : 66Mean 800Range 30- 2 000

ConfrolsMumDer 94Mean 650Range 25-2 200

Eosinopnils/;il (x 10')

Fig. 2. Blood eosinophil counts in asthmatics plus non-asthmatic atopies and normal subjects.

298 D. I. Grove, T. O. Bitr.ston ami I. J. Forbes

10,000 r

1000

100

• " .

100 10 00 10,000 100,000

IqE (u/ml)

Fig. 3. Correialinn between serum IgE and blood eosinophil counts; irepresents asthmatic and atopic subjects.

represents normal subjects; O

not clear (Sinclair, 1970; Kelly. 1973). Helminth infestation in animals, in addition loinducing a reaginic response to helminth antigens, potentiates antibody responses tonon-helminlh antigens (Orr & Blair. 1969; Jarrett & Stewart. 1972). The role of IgE inhuman helminthiasis is obscure despite a constant relationship (Somei, Muneo &Tomio, 1972).

Although blood levels do not necessarily retlect tissue activity, the raised serumIgE levels may represent increased immediate hypersensitivity reactions in the tissues.The relatively higher IgE levels in the non-asthmatic atopic and asthmatic groups mayrepresent increased titres of antibody to non-helminth antigens, hookworm-specificantigens, or both. The non-asthmatic atopic and asthmatic populations presumablyrespond in greater degree to non-helminth antigens as in other parts ofthe world.The raised IgE levels in these groups may thus simply represent the addition of hel-minth antibodies to an already high IgE level. Alternatively, the raised IgE levels mayresult from higher titres of hookworm-specific antibodies as a manifestation ofincreased reaginic responsiveness to any antigen. If so. this may have no functionalsignificance. When taken in conjunction with reduced hookworm egg output in thesegroups, however, the higher IgE levels are consistent with the hypothesis that atopicindividuals are more succe.ssful in controlling helminth infestation by virtue of anincreased efficiency in IgE responsiveness to helminth antigens.

The mechanism of this resistance may be the release of biologically active amines.e.g. histamine and 5 hydroxytryptamine which render the environment unsuitable forthe parasite (Kelly. 1973). Atopic individuals may produce more specific IgE withincreased release of amines.

Speculationcontinuesas to the roieof the eosinophil (leading article, L«/jn'r. 1971).It has been shown that eosinophils phagocytose antigen antibody complexes (Sabesin.1963). Biologically active amines are chemotactic to eosinophils (Archer, 1963). Theeosinophiiic response to histamine may be less in non-atopic than atopic individuals(Feinberg, Eeinberg & Lee. 1966). ll has been stated that eosinophilia and antiparasite

IgE, eosinophils, atopy and hookworm 299

immune reactions are separable phenomena (leading article. Lancet. 1971). There is,however, a correlation between eosinophilia and IgE levels in both the normal andatopic-asthmatic groups. Furthermore, the relatively higher IgE levels in the asthmaticand non-asthmatic atopic groups are paralleled by a relatively greater eosinophilia inthese groups. The eosinophilia could be a direct response to an antigenic stimulus ormay be a second order phenomenon, such as a consequence ofthe presence of freeamines, antigen-antibody complexes, or release of lymphokines.

These results are consistent with the hypothesis that a function ofthe IgE-mediatedimmune system is to assist in control of helminth infestation, but carrying with il apropensity to atopic disease.

AcknowledgmentsWe wish to thank Dr R. W. Hornabrook. Director, Papua New Guinea Institute ofMedical Research for his co-operation.

This study was supported by the Clive & Vera Ramaciotti Foundations. Dr Groveis a Postgraduate Medica! Research Scholar of the National Health & MedicalResearch Council of Australia.

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