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Immune Cell Alterations and PI3K-PKB Pathway Suppression in Patients with Allergic Rhinitis Undergoing Sublingual Immunotherapy

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Abstract

Introduction

Our prior clinical study assessed the efficacy and safety of sublingual immunotherapy (SLIT) with standardized Dermatophagoides farina drops on patients with allergic rhinitis (AR) while analyzing the characteristics of adverse reactions. This study was conducted to evaluate the immune cell composition alterations in AR patients before and after SLIT, and to comprehensively investigate the role and changes of antigen-specific immune cells associated with treatment efficacy.

Methods

A total of 68 AR patients who completed 12 months of SLIT were included in the study. Before the trial’s initiation and after 1 year of SLIT, 10 ml of venous blood was collected. Peripheral blood mononuclear cells were isolated using the Ficoll gradient method. The mRNA transcriptome was analyzed using an Affymetrix microarray. The proportions of 22 immune cell types were calculated via the CIBERSORTx platform. Correlations between each immune cell type and SLIT were analyzed. PI3K-PKB pathway dysregulation were analyzed using quantitative PCR and Western blot. Flow cytometry was utilized to assess the percentages of Th1 and Th2 cells.

Results

Mono-sensitized AR patients exhibited marked increases in plasma cells, activated memory T cells, regulatory T cells, and activated dendritic cells, while experiencing decreased neutrophils and resting dendritic cells. In poly-sensitized AR patients, the most notable change was an increase in regulatory T cells, coupled with decreased T follicular helper cells, resting dendritic cells, and activated mast cells. These findings indicated that SLIT reshaped immune cell profiles in AR patients, and, notably, the specific changes differed between mono-sensitized and poly-sensitized individuals. Furthermore, SLIT appeared to shift the immune response towards a Th2 decrease profile in both groups. Importantly, suppression of the PI3K-PKB pathway was evidenced as inhibition of PKB phosphorylation and the decrease of glycogen synthase kinase 3 β (GSKβ) and mammalian target of rapamycin (mTOR) expression after SLIT.

Conclusion

Our study has demonstrated that SLIT treatment led to distinct changes in immune cell profiles between mono-sensitized and poly-sensitized AR patients. Furthermore, SLIT appeared to reduce a Th2 immune response, highlighting its efficacy in AR treatment. Importantly, the study revealed the suppression of the PI3K-PKB pathway, shedding light on the immunological mechanisms underlying SLIT’s effectiveness.

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Data Availability

The datasets during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Authorship Contributions

Xinxin Zhang, Geping Wu, Xingkai Ma, and Lei Cheng participated in acquisition/collection of data and analysis or interpretation of data. Xinxin Zhang, Geping Wu, Xingkai Ma, and Lei Cheng participated in analysis or interpretation of data. Xinxin Zhang, Geping Wu, Xingkai Ma, and Lei Cheng participated in drafting the publication and/or revising it critically for important intellectual content and approved the final version for submission.

Authorship

All named authors meet the ICMJE criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Funding

This study was supported by the Key Discipline Construction Project of Suzhou City, Project Number: SZXK202119. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The journal’s Rapid Service Fee was purchased using funding provided by the study sponsor.

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Authors and Affiliations

  1. Department of Otolaryngology, Zhangjiagang Hospital Affiliated to Soochow University, Suzhou, 215600, China

    Xinxin Zhang, Geping Wu & Xingkai Ma

  2. Department of Otorhinolaryngology and Clinical Allergy Center, The First Affiliated Hospital, Nanjing Medical University, Nanjing, 210029, China

    Lei Cheng

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Correspondence to Geping Wu or Lei Cheng.

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Conflict of interest

Xinxin Zhang, Geping Wu, Xingkai Ma, and Lei Cheng declare that they have no conflict of interest.

Compliance with ethics guidelines

The study was performed in accordance with relevant guidelines and regulations, following the approval of the licensing committee of Zhangjiagang Hospital affiliated to Soochow University, Suzhou, China (IRB#: ZJG7714; date of approval: 13 September 2018), and conformed to the tenets of the Declaration of Helsinki. Written informed consent was obtained from all participants. We thank the participants of the study.

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Zhang, X., Wu, G., Ma, X. et al. Immune Cell Alterations and PI3K-PKB Pathway Suppression in Patients with Allergic Rhinitis Undergoing Sublingual Immunotherapy. Adv Ther 41, 777–791 (2024). https://doi.org/10.1007/s12325-023-02747-z

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