Combined IMIG and Immune Ig Attenuate Allergic Responses in Beagle Dogs.

R M Gorczynski,G Hoffmann,T Maqbool

doi:10.1155/2020/2061609

Abstract

Background We previously reported attenuation of serum OVA-specific IgE levels and of lymphocyte-derived IL-4, both nominal markers of allergic immunity, following injection of a combination of homologous (mouse) polyclonal anti-idiotypic immunoglobulin (Ig) and immune Ig in BALB/c mice. We predicted this might generalize to other species and using heterologous mixtures of Igs. This was assessed in mice using OVA sensitization in the presence of human Igs as a source of both anti-idiotype Ig and immune Ig and in dogs with peanut butter-induced allergic responses. Methods Eight-week-old BALB/c mice received OVA immunization and 5 weekly injections of immune Ig or anti-idiotype Ig from either homologous (mouse) or heterologous (human) sources. Five-month-old Beagles received weekly topical exposure (on the abdomen) to peanut butter and treatment with pooled dog Ig and dog antirabies immune Ig, or a combination of human IMIG and human anti-Tet. All mice/dogs thereafter received a final allergen challenge, and serum IgG, IgE, and allergen-induced IL-2/IL-4 and IL-31 production in 72 hr cultures was measured. Results In mice attenuation of OVA-induced allergy (IgE-specific Ig and OVA-induced IL-4) was seen using both mouse and human Ig mixtures, without effect on OVA serum IgG or OVA-induced IL-2. Attenuation of concanavalin A- (ConA-) induced IL-4 : IL-2 production and of peanut butter-induced IL-4 and IL-31 was seen in dogs receiving combinations of both heterologous and homologous immune Igs and anti-idiotype Igs, with no decline in IL-2 production. Allergen-specific IgE/IgG was not detectable in dog serum, but there was a trend to lower total serum IgE levels (and decreased IgE : IgG ratios). Conclusion Homologous and heterologous combinations of polyclonal IMIG and immune Ig attenuate allergic responses in mice and dogs. This treatment protocol represents a novel approach which can be adapted for allergic desensitization in veterinary and human use.

Highlights

Allergic rhinitis, asthma, and atopic eczema are among the commonest causes of chronic ill health, with a combined prevalence of 10-20% [1,2,3]
Following a final boost with OVA after these 5 Ig injections, mice were sacrificed 7 d after OVA, and serum IgG/IgE to OVA was detected by ELISA, with IL-2 and IL-4 levels detected at 72 hr from OVA-stimulated splenocytes
There was a trend to an increased IgG to IgE ratio after peanut butter sensitization in dogs treated with the combined dog or human Igs, which reached significance for the group treated with human Igs (Figure 5(e)), implying a relative decrease in IgE levels in this group

Summary

Background

We previously reported attenuation of serum OVA-specific IgE levels and of lymphocyte-derived IL-4, both nominal markers of allergic immunity, following injection of a combination of homologous (mouse) polyclonal anti-idiotypic immunoglobulin (Ig) and immune Ig in BALB/c mice. We predicted this might generalize to other species and using heterologous mixtures of Igs. We predicted this might generalize to other species and using heterologous mixtures of Igs This was assessed in mice using OVA sensitization in the presence of human Igs as a source of both anti-idiotype Ig and immune Ig and in dogs with peanut butter-induced allergic responses. This treatment protocol represents a novel approach which can be adapted for allergic desensitization in veterinary and human use

Introduction

Preliminary Studies in Mice

Results

Discussion

Conflicts of Interest