Allergen Immunotherapy–Induced Immunoglobulin G4 Reduces Basophil Activation in House Dust Mite–Allergic Asthma Patients

Abstract

It is unclear if allergen immunotherapy (AIT) can reduce allergy effector cell activation. We evaluated the basophil response during Dermatophagoides pteronyssinus (Der p) subcutaneous immunotherapy (SCIT) and its relationship to allergen-specific immunoglobulin G4 (sIgG4) in allergic rhinitis and/or asthma patients. The study included 55 subjects, of which 35 cases received Der p SCIT and 20 controls received standard medications. Symptom and medication scores (SMSs), sIgG4 levels, specific immunoglobulin E (sIgE) levels, allergen-induced basophil activation tests (BATs) in whole blood, and BAT inhibition assays in serum were determined at weeks 0, 4, 12, 16, 52, and 104 of SCIT. Levels of Der p sIgG4 in SCIT patients significantly increased after 12 weeks of treatment compared to week 0. Serum obtained from SCIT patients significantly inhibited basophil activation after 12 weeks of treatment. Removal of immunoglobulin G4 (IgG4) antibodies at week 104 reduced the ability of serum to block basophil activation. An increase of Der p sIgG4 rather than reduction of Der p sIgE correlated with the reduction of basophil activation during SCIT. The sIgG4 antibodies may compete with sIgE binding to allergens to form an immunoglobulin E (IgE)-allergen complex. SCIT reduced the sensitivity of allergen-triggered basophil activation in Der p allergic rhinitis and/or asthma patients through induction of sIgG4.

Efficacy and Safety of Subcutaneous Immunotherapy for Local Allergic Rhinitis: A Meta-Analysis of Randomized Controlled Trials

“…29 The IgG isotype is regarding as a blocking antibody, which competes with IgE for the same epitope and binds to allergens. 33–37 Therefore, we extracted the data of allergen tolerance by NAPT, serum sIgE and sIgG4 as objective responses. However, the data is not sufficient to make the meta-analysis because of the different measurement units; we finally make a summary for the trend of these immunologic response results.…”

Basophils and their effector molecules in allergic disorders

“…8 Oral immunotherapy against peanut and grass pollen allergens reportedly elevates serum levels of allergen-specific IgG4, [48][49][50][51][52] that appear to suppress basophil activation after immunotherapy. 53,54 Thus, IgG4 class-switched allergen-specific antibodies contribute to the suppression of basophil/ mast cell activation, leading to the improvement of allergic diseases. IL-3-primed human basophils have been demonstrated to be activated when treated with intravenous immunoglobulin (IVIG) via the crosslink of IgE/FcεRI by anti-IgE autoantibodies present in IVIG.…”

“…In contrast, human basophils are rather suppressed by IgG via inhibitory FcγRIIB receptors, most likely due to the predominant expression of inhibitory IgG receptors over activating IgG receptors on human basophils 8 . Oral immunotherapy against peanut and grass pollen allergens reportedly elevates serum levels of allergen‐specific IgG4, 48‐52 that appear to suppress basophil activation after immunotherapy 53,54 . Thus, IgG4 class‐switched allergen‐specific antibodies contribute to the suppression of basophil/mast cell activation, leading to the improvement of allergic diseases.…”

Principles, potential, and limitations of ex vivo basophil activation by flow cytometry in allergology: A narrative review

“…54,64 BATs have also been used to monitor allergenspecific immunotherapy (AIT) for house dust mite, birch, timothy grass, Lolium perenne, mugwort, Parietaria, Japanese cedar, and cypress. [65][66][67][68][69] In these studies, reduced basophil sensitivity occurs early during AIT and is likely due to interference of blocking IgG antibodies. Results are obtained from individuals responsive to positive control stimulation and expressed as a percentage of CD63 1 basophils; the dashed rectangle denotes 1 mg/mL as being the most discriminative stimulation concentration (left).…”