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The role of IgG in allergy and tolerance to common food allergens
Project Code: T07032
Department of Allergy, Cambridge University Hospitals Trust
Clark, A ; Tay, S; Deigton, J; King, Y; Ewan, P
The clinical significance of food-specific IgG subclasses in food allergy and tolerance remains unclear. This project investigates the role of IgG in egg and peanut allergy, and in a further group with resolved allergy.
We recruited subjects with peanut (n=59) and/or egg allergy (n=40) from our allergy clinic and clinical database. Subjects had a recent clear history of an acute allergic reaction to either peanut or egg and evidence of egg or peanut specific IgE. Subjects were characterised by clinical interview and blood was taken for RAST IgE assays and ELISA IgG assays. Subjects with egg allergy underwent oral challenge. Assays were developed to measure amounts of serum IgG, G1 and G4 to Ovalbumin ( OVA , the major egg allergen) and crude peanut extract.
Egg-specific IgE and Skin Prick Test (SPT) weal diameters were significantly higher in the allergic group compared to the resolved group. OVA and peanut-specific IgG was detected in all allergic and non-allergic subjects alike. OVA IgG levels were higher than crude peanut extract (CPE) IgG in non allergic controls (median μg/ml IgG = 15.9 vs. 2.2, IgG1= 1.3 vs. 0.6, IgG4 = 7.9 vs. 0.7; p<0.01). There were no differences in OVA IgG levels between egg-allergic (n=40), egg-resolved (n=22) and control (n=18) subjects. In contrast, peanut-specific IgG were significantly higher in peanut-allergic subjects compared to non-allergic controls and to non-peanutsensitised but egg-allergic subjects (n=26; median μg/ml IgG = 17.0, IgG1 = 3.3, IgG4 = 5.2). Overall, the range of IgG4 was greater than IgG1, and IgG4 was the dominant subclass in >60% of all subjects.
Serum specific IgE and positive specific SPT indicate sensitisation to a specific food allergen. In egg allergy, we have shown the level of specific IgE or size of SPT wheal can distinguish between clinically active allergy and resolution.
We have developed an ELISA system whereby measurements of specific IgG can be made in absolute values rather than arbitrary units; this has the advantage of providing a linear measurement in μg/ml which can be compared between IgG subclasses and for different antigens. Further, as other groups adopt this technique our results may be compared with theirs.
We identified that levels of OVA-specific IgG are similar in egg-allergic, egg-resolved and non-allergic control subjects, suggesting that levels of OVA-specific IgG are a marker of exposure, rather than clinical egg allergy. Higher peanut-specific IgG levels are associated with clinical allergy, compared to non allergics but the range of IgG titres of the allergic and control groups overlap significantly. Hence, these measurements are not of diagnostic value.
OVA IgG is detected in all subjects but levels of OVA specific IgG were 10-fold higher than peanut specific IgG in the same non-atopic controls. This may be explained by the relatively early introduction of higher doses of egg into children’s diets compared to peanut. High levels of milk-specific IgG have also been reported in infancy, during the time of highest milk ingestion.
Strong IgG responses to egg may be a normal physiological response to a protein frequently ingested from infancy, whereas upregulated IgG responses in peanut allergy may be indicative of a dysregulated immune response to peanut allergens. Test for specific IgG to egg and peanut are of no diagnostic use.
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