Relationship between allergic status and specificity of IgG antibody to inhaled allergens: the grass pollen model

Background We have previously reported that IgG antibodies from healthy ind ividuals and patients suffering from non-seasonal mite allergy bind to diff erent sets of epitopes on Der p 1, allowing almost complete discrimination of the populations. Objectives To confirm this observation in a seasonal allergy model where a clear relationship between allergic symptoms and exposure to the offending agent is established. To investigate whether the pattern of modified specif icity is related to the differences in IgG subclass hierarchy usually exhib ited by nonallergic and allergic populations. Methods The capacity of individual sera from patients allergic to grass pol len and healthy individuals, including grass pollen-sensitized subjects, to prevent the binding of pooled Igc, IgG1, and IgG4 fractions from grass pol len-allergic patients and healthy individuals to solid-phase bound grass po llen antigen was evaluated in enzyme-linked immunosorbent assay (ELISA) usi ng streptavidin-biotin technology. Specificity controls were pet-formed usi ng sera from patients allergic to cat dander and house dust mite. Results The capacity of sera to prevent the antigen binding of allergic IgG averaged 84 +/- 5% for allergic sera and 53 +/- 6% for healthy sera (P<0.0 01 by one-way ANOVA). Conversely, using the antigen-binding capacity of hea lthy control IgG as reference, percentage inhibitions averaged 46 +/- 9% in grass pollen-allergic subjects compared with 80 +/- 4%, 82 +/- 2% in healt hy individuals, and mite- and cat-allergic patients, respectively, resultin g in two well-separated populations (P<0.0001 by one-way ANOVA). Similar re sults were found regardless of whether pooled IgG1 or IgG4 were used. Conclusion Together with previous data, our results define a new type of hu moral signature in the immune response to inhaled allergens. Allergic and h ealthy status differ not only in the presence or absence of specific IgE an tibody but also in the preferential expression of distinct IgG specificitie s that are better correlated with clinical manifestations and are unrelated to subclass distribution.