The Molecular Pathology of IgG₄ in Allergic Conditions

Abstract

In the time available. I have built up a picture of the molecular pathology of IgE antibodies; and considered that of IgG4 antibodies in comparison. As will have become apparent, much less direct evidence is available on the latter; partly because of the lack of reliable and relevant in vitro functional assays. Nevertheless, I hope that in speculating on the possible molecular pathology of IgG4 antibodies. I have said enough to convince you that their likely mode of action in immediate-type hypersensitivity reactions will prove to be fundamentally different to that of IgE antibodies. It is important to bear this in mind in attempts to devise suitable assays of use in clinical diagnosis; and in considering their unique contributions to allergic reactions.

High IgG4 antibody level is associated with failure of immunotherapy with inhalant allergens

“…The data presented in this paper lend some support to the hypothesis that IgG4 Abs may be sensitizing in some patients (reviewed and discussed in [19][20][21]). As only nine of nineteen patients with high IgG4 Ab level at the end of IT failed to improve, or became worse, other factors than the absolute or relative concentration of IgG4 Abs may be important in determination of their sensitizing ability.…”

The Role of Antiglobulins in IgG4-Mediated Allergic Diseases

“…5 Thus, it is possible that this heterogeneity reflects either antigenic differences (i.e. IgG4a and IgG4b) that have been reported to exist amongst human IgG4 proteins,6 or differences in Fc-bound oligosaccharide composition.…”

IgG4 Antibodies in Hay Fever Patients

“…The histamine release process can be exerted, however, by antiserum against IgG4 [2,3,5]. In patients degranulation of target cells, it is sug gested to arise from the 'mixed' interaction of an al lergen with IgG4 and IgE antibodies fixed on the cell wall, or with fixed IgG4 antibodies and rheumatoid factor [2,3]. Not only anaphylactic but also protective function can be associated with IgG4.…”

“…The IgG4 antibodies are cytophylic for mast cells and basophils [4], but in vitro they cannot trigger degranulation of these cells by the relevant allergen, apparently due to the low affinity of these antibodies and insufficient cross-linking of cell-bound IgG4 with an allergen. The histamine release process can be exerted, however, by antiserum against IgG4 [2,3,5]. In patients degranulation of target cells, it is sug gested to arise from the 'mixed' interaction of an al lergen with IgG4 and IgE antibodies fixed on the cell wall, or with fixed IgG4 antibodies and rheumatoid factor [2,3].…”

“…The mechanism of IgE antibody action is comprehended well enough [1,2], but many aspects of IgG4 function remain obscure [2,3]. The IgG4 antibodies are cytophylic for mast cells and basophils [4], but in vitro they cannot trigger degranulation of these cells by the relevant allergen, apparently due to the low affinity of these antibodies and insufficient cross-linking of cell-bound IgG4 with an allergen.…”