Broad immunogenicity of house dust mite proteins contrasts restricted
specific IgE and IgG4 associated with allergy
Abstract
Background: House dust mite (HDM) allergy involves IgE and T
H2 responses to major and minor allergens. Less is known
about the involvement of other immune pathways and the potential role of
other HDM proteins in allergic disease. In this study, the association
between HDM allergy and immune responses to the HDM proteome was
investigated. Methods: The HDM proteome was represented by 40 purified
recombinant HDM proteins (19 known allergens and 21 novel proteins).
T-cell responses to HDM proteins were determined ex vivo and
antibody responses (IgA, IgE, IgG and IgG4) were measured using micro
arrays and basophil activation in 21 HDM allergic donors and 16
non-allergic controls. Changes in specific IgE, IgG and IgG4 during SQ
HDM SLIT-Tablet immunotherapy was assessed in 38 subjects with allergic
asthma. Results: HDM proteins were broadly immunogenic inducing
comparable IgG, IgA, and non-T H2 cytokine responses in
both allergic and non-allergic individuals. Specific IgE, IgG4 and T
H2 cytokine responses were largely restricted to the
allergic donors. IgE and IgG4 were primarily directed to known major
allergens and overlapping in specificity whereas cellular T
H2 responses extended beyond the known HDM allergens.
Individual proteins displayed distinct immunological profiles. HDM
sublingual immunotherapy increased the levels of specific IgE and IgG4
but did not change the overall pattern of recognition. Conclusion: HDM
proteins are highly immunogenic and give rise to complex patterns of
immune recognition also in the absence of allergy. This has potential
implications for the pathogenesis of HDM allergy and the mode of action
of allergy immunotherapy.