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

Qiujuan Su; Nina Ren; Mulin Feng; Xueni Zeng; Yan Dong; Mo Xian; Xu Shi; Tian Luo; Gang Liu; Jing Li

doi:10.1016/j.waojou.2022.100715

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

World Allergy Organ J. 2023 Jan 26;16(1):100715. doi: 10.1016/j.waojou.2022.100715. eCollection 2023 Jan.

Authors

Qiujuan Su¹, Nina Ren^{1

2}, Mulin Feng³, Xueni Zeng¹, Yan Dong¹, Mo Xian¹, Xu Shi¹, Tian Luo¹, Gang Liu⁴, Jing Li^{1

3}

Affiliations

¹ Department of Allergy and Clinical Immunology, Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
² Department of Respiratory Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.
³ Yangjiang Key Laboratory of Respiratory Disease, Department of Respiratory Medicine, People's Hospital of Yangjiang, Yangjiang, China.
⁴ Clinical Research Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.

Abstract

Background: The modulations of lymphocyte subsets and cytokine production due to subcutaneous allergen immunotherapy (SCIT) are not fully clarified.

Objective: We 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.

Methods: This 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.

Results: We 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.

Conclusion: SCIT induced Dep-p sIgG4 may be involved in downregulating Th2 cytokine production in Der-p allergic asthma patients.

Keywords: Allergen specific immunotherapy; Asthma; Regulatory T cells; Rhinitis; T helper cells.