Specific immunoglobulin G4 correlates with Th2 cytokine reduction in patients with allergic asthma treated by Dermatophagoides pteronyssinus subcutaneous immunotherapy

Abstract

BackgroundThe modulations of lymphocyte subsets and cytokine production due to subcutaneous allergen immunotherapy (SCIT) are not fully clarified. ObjectiveWe investigated the changes in T-lymphocyte subsets and serum Dermatophagoides pteronyssinus-specific immunoglobulin G4 (Der-p sIgG4), as well as cytokine production during Der-p SCIT, in patients with allergic asthma. MethodsThis study involved 20 patients with allergic asthma who were receiving 156-week Der-p SCIT and 20 patients without SCIT (non-SCIT). We measured symptom and medication scores (SMS), serum Der-p sIgG4 levels, CD4+CD25+Foxp3+ T regulatory (Treg), CD4+IL-4−IFN-γ+ T-helper (Th) 1, and CD4+IL-4+IFN-γ− Th2 lymphocyte percentages in peripheral blood mononuclear cells (PBMCs) with/without Der-p extract stimulation at weeks 0, 4, 12, 16, 52, 104, and 156. Cytokine release inhibition assays were performed by incubation with serum from SCIT and non-SCIT patients, Der-p allergen, and PBMCs. Levels of interleukin (IL)-4, IL-5, IL-10, IL-13, IL-17, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-β1 were evaluated in supernatant. ResultsWe found that SCIT patients had significantly lower SMS after week 52. Der-p sIgG4 levels in SCIT patients significantly increased at week 16 compared with non-SCIT subjects. CD4+IL-4+IFN-γ− Th2% in SCIT patients showed a significant decrease from weeks 104–156 compared with week 0, while no change was observed in CD4+CD25+Foxp3+ Treg and CD4+IL-4−IFN-γ+ Th1 percentages. IL-5, IL-13, IL-4, IL-17, and TNF-α levels in supernatant of PBMCs cultured with serum of SCIT patients after 16 weeks showed significant lower levels compared with non-SCIT patients, and showed significant reverse associations with Der-p sIgG4 levels. ConclusionSCIT induced Dep-p sIgG4 may be involved in downregulating Th2 cytokine production in Der-p allergic asthma patients.