Abstract
BackgroundTwo conditions are used as markers of atopy: the presence of circulating anti-allergen IgE antibodies and the presence of positive skin prick test (SPT) reactions to allergenic extracts. The correlation between these conditions is not absolute. This study aimed at investigating immunological parameters that may mediate this lack of correlation. Individuals whose sera contained anti-B. tropicalis extract IgE antibodies (α-BtE IgE) were divided into two groups, according to the presence or absence of skin reactivity to B. tropicalis extract (BtE). The following parameters were investigated: total IgE levels; α-BtE IgE levels; an arbitrary α-BtE IgE/total IgE ratio; the proportion of carbohydrate-reactive α-BtE IgE; the proportion of α-BtE IgE that reacted with Ascaris lumbricoides extract (AlE); the production of IL-10 by BtE- and AlE-stimulated peripheral blood cells (PBMC).ResultsTotal IgE levels were similar in the two groups, but α-BtE IgE was significantly higher in the SPT-positive group (SPT+). A large overlap of α-BtE IgE levels was found in individuals of both groups, indicating that these levels alone cannot account for the differences in SPT outcome. Individuals of the two groups did not differ, statistically, in the proportion of α-BtE IgE that reacted with carbohydrate and in the production of IL-10 by BtE- and AlE-stimulated PBMC. Both groups had part of α-BtE IgE activity absorbed out by AlE, indicating the existence of cross-reactive IgE antibodies. However, the α-BtE IgE from the SPT-negative individuals (SPT-) was more absorbed with AlE than the α-BtE IgE from the SPT+ individuals. This finding may be ascribed to avidity differences of the α-BtE IgE that is present in the two groups of individuals, and could occur if at least part of the α-BtE IgE from the SPT- individuals were elicited by A. lumbricoides infection.ConclusionThe present results suggest that a low ratio of specific IgE to total IgE levels (in a minority of individuals), and differences in α-BtE IgE avidities (which would have high affinities for A. lumbricoides antigens in SPT- than in SPT+ individuals) may play a role in the down-modulation of type-I hypersensitivity reaction against aeroallergens described in helminth-infected individuals.
Highlights
Two conditions are used as markers of atopy: the presence of circulating anti-allergen IgE antibodies and the presence of positive skin prick test (SPT) reactions to allergenic extracts
Anti-B. tropicalis extract (BtE) IgE levels and their correlation with wheal sizes of SPT reactions The SPT-positive individuals had higher aBtE IgE levels than the SPT-negative individuals, a great overlap in these antibody levels could be seen between the two groups (p < 0.05; Mann-Whitney U test, Figure 1A)
Overall, a-BtE IgE levels were found to be directly related to positivity in the BtE SPT and with the average diameter of the BtE SPT wheal
Summary
Two conditions are used as markers of atopy: the presence of circulating anti-allergen IgE antibodies and the presence of positive skin prick test (SPT) reactions to allergenic extracts. The correlation between these conditions is not absolute. Several hypotheses have been proposed to explain why, in some individuals with sIgE, contact of skin mast cells with allergen does not lead to their degranulation Some of these hypotheses involve: (i) the competition of polyclonal IgE raised by helminths with sIgE for mast-cell Fcε receptors [11]; (ii) anti-allergen IgG4 antibodies blocking IgE-mediated immunity and allergic processes [12]; (iii) presence of cross-reactive IgE antibodies that react with glycoprotein carbohydrate moieties [a(1,3)-fucose and ß(1,2)-xylose on N-glycans], which are widely present in plants and invertebrates and produce clinically irrelevant antibodies [13]; (iv) the induction of regulatory CD4+ CD25+ Foxp3+ T cells that are capable of down-regulating the allergic process [14]
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