Circulating T follicular helper 2 cells, T follicular regulatory cells and regulatory B cells are effective biomarkers for predicting the response to house dust mite sublingual immunotherapy in patients with allergic respiratory diseases

Katsunori Shigehara; Ryuta Kamekura; Ippei Ikegami; Hiroshi Sakamoto; Masahiro Yanagi; Shiori Kamiya; Kentaro Kodama; Yuichiro Asai; Satsuki Miyajima; Hirotaka Nishikiori; Eiji Uno; Keisuke Yamamoto; Kenichi Takano; Hirofumi Chiba; Hirofumi Ohnishi; Shingo Ichimiya

doi:10.3389/fimmu.2023.1284205

Circulating T follicular helper 2 cells, T follicular regulatory cells and regulatory B cells are effective biomarkers for predicting the response to house dust mite sublingual immunotherapy in patients with allergic respiratory diseases

Front Immunol. 2023 Nov 24:14:1284205. doi: 10.3389/fimmu.2023.1284205. eCollection 2023.

Authors

Katsunori Shigehara^#^{1

2

3}, Ryuta Kamekura^#^{1

4}, Ippei Ikegami¹, Hiroshi Sakamoto^{1

4}, Masahiro Yanagi^{1

2}, Shiori Kamiya^{1

5}, Kentaro Kodama², Yuichiro Asai², Satsuki Miyajima², Hirotaka Nishikiori², Eiji Uno³, Keisuke Yamamoto⁴, Kenichi Takano⁴, Hirofumi Chiba², Hirofumi Ohnishi⁶, Shingo Ichimiya¹

Affiliations

¹ Department of Human Immunology, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
² Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, Sapporo, Japan.
³ Ai Medical Clinic, Sapporo, Japan.
⁴ Department of Otolaryngology and Head and Neck Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan.
⁵ Department of Dermatology, Sapporo Medical University School of Medicine, Sapporo, Japan.
⁶ Department of Public Health, Sapporo Medical University School of Medicine, Sapporo, Japan.

^# Contributed equally.

Abstract

The relationships between T follicular helper (Tfh) cells and antigen-specific immunoglobulins (sIgs) in patients with allergic respiratory diseases who are receiving antigen immunotherapy (AIT) have not been fully clarified. Therefore, we started to perform house dust mite sublingual immunotherapy (HDM-SLIT) for 20 patients with atopic asthma comorbid with allergic rhinitis (AA+AR) who were already receiving ordinary treatments including inhaled corticosteroid (ICS). We examined percentages of circulating T follicular helper (cTfh) and regulatory (cTfr) cells and percentages of circulating regulatory T (cTreg) and B (cBreg) cells by FACS and we examined levels of Der-p/f sIgs by ELISA. Based on the symptom score (asthma control questionnaire: ACQ) and medication score ((global initiative for asthma: GINA) treatment step score) in patients with AA, the patients were divided into responders and non-responders. The percentage of cTfh2 cells significantly decreased and the percentage of cTfh1 cells significantly increased within the first year. Der-p/f sIgEs decreased after a transient elevation at 3 months in both groups. Notably, the percentage of cTfh2 cells and the ratio of cTfh2/cBreg cells and Der-p/f sIgEs greatly decreased in responders from 6 months to 12 months. The percentages of cTfr and cTreg cells showed significant negative correlations with the percentage of cTfh2 cells. The percentage of IL-4⁺ cTfh cells were significantly decreased and the percentage of IFN-γ⁺ cTfh cells were increased before treatment to 24 months in 6 patients examined (4 responders and 2 non-responders). We performed multi plelogistic regression analysis based on these results, the ratios of cTfh2/cTfr cells and cTfh2/cBreg cells at the start of therapy were statistically effective biomarkers for predicting the response to HDM-SLIT in patients with AA+AR.

Keywords: B regulatory cells; Der-p/f-specific Igs; T follicular helper cells; T follicular regulatory cells; house dust mite SLIT.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Asthma*
B-Lymphocytes, Regulatory*
Biomarkers
Dermatophagoides pteronyssinus
Humans
Pyroglyphidae
Respiration Disorders*
Sublingual Immunotherapy*
T Follicular Helper Cells
T-Lymphocytes, Regulatory

Substances

Biomarkers

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by grants-in-aid for scientific research from Japan Society for Promotion of Science including #18K08381 (KS), #21K08441 (KS), #21K09658 (RK), #18H02632 (SI) and #22K09670 (KY).