CD38⁺ B cells affect immunotherapy for allergic rhinitis - 04/05/22

Doi : 10.1016/j.jaci.2022.01.012

Gui-Xiang Tian, MD, PhD ^a,^b, Ke-Ping Peng, MD ^c,^⁎ , Ming-Hui Liu, MD ^a,^b, Dao-Fa Tian, MD, PhD ^c, Hai-Qing Xie, MD ^a, Li-Wen Wang, MD ^a, Yu-Yang Guo, MD ^a, Shan Zhou, MD ^a, Li-Hua Mo, PhD ^d,^e, Ping-Chang Yang, MD, PhD ^d,^e,^f,^⁎
^a Department of Ultrasound, The Second Xiangya Hospital of Central South University, Changsha, China
^b Research Center of Ultrasonography, The Second Xiangya Hospital of Central South University, Changsha, China
^c Department of Otorhinolaryngology–Head and Neck Surgery, The First Hospital of Hunan University of Chinese Medicine, Changsha, China
^d Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Shenzhen, China
^e Institute of Allergy & Immunology, Shenzhen University School of Medicine, State Key Laboratory of Respiratory Disease Allergy Division at Shenzhen University, Shenzhen, China
^f Longgang ENT Hospital & Shenzhen ENT Institute, Shenzhen, China

^∗Corresponding authors: Ke-Ping Peng, MD, Department of Otorhinolaryngology–Head and Neck Surgery, The First Hospital of Hunan University of Chinese Medicine, Changsha 410007, Hunan Province, China.Department of Otorhinolaryngology–Head and Neck SurgeryThe First Hospital of Hunan University of Chinese MedicineChangshaHunan Province410007China^∗∗Ping-Chang Yang, Room A7-509, Lihu Campus, Shenzhen University School of Medicine. 1066 Xueyuan Blvd, Shenzhen 518055, China.Room A7-509Lihu CampusShenzhen University School of Medicine. 1066 Xueyuan BlvdShenzhen518055China

Abstract

Background

Allergen-specific immunotherapy (AIT) is the mainstay in the treatment of allergic diseases, but the therapeutic effects of AIT need to be improved. CD38⁺ B cells are an immune cell fraction involved in the pathogenesis of allergic diseases as well as in immune regulation.

Objective

We sought to elucidate the role of antigen-specific CD38⁺ B cells in AIT.

Methods

An analysis was carried out on AIT results of 48 patients with perennial allergic rhinitis (AR), among which peripheral blood immune cells were analyzed by flow cytometry; serum cytokine levels were determined by ELISA. An AR murine model was developed to test the role of CD38⁺ B cells in AIT.

Results

A fraction of antigen-specific CD38⁺ B cell was detected in AR patients. CD38⁺ B-cell frequency was negatively correlated with the therapeutic effects of AIT. A negative correlation was detected between the CD38⁺ B-cell frequency and regulatory T-cell frequency in AR patients treated with AIT. Exposure to specific antigens induced CD38⁺ B cells to produce IL-6, that converted Treg cells to T_H17 cells. Coadministration of anti-CD38 antibody significantly promoted the therapeutic effects of AIT.

Conclusions

Antigen-specific CD38⁺ B cells compromise AIT effects by producing IL-6 to convert regulatory T cells to T_H17 cells. Inhibition of CD38⁺ B cells promotes the effects of AIT.

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Key words : Allergy, immunotherapy, CD38, B cell, regulatory T cell

Abbreviations used : Ab, AIT, AR, BSA, DME, EPX, FACS, HC, HDM, IQR, NLF, PBMC, Tfr, TNSS

Plan

Methods

Human subjects

Allergen-specific immunotherapy

Total nasal symptom score

Statistical analysis

Results

Peripheral antigen-specific CD38⁺ B-cell frequency is higher in AR patients

CD38⁺ B-cell frequency is negatively associated with the effects of AIT

CD38⁺ B cells negatively correlate with immune regulatory activities in AR patients treated with AIT

Exposure to specific antigens induces CD38⁺ B cells to produce IL-6

CD38⁺ B cells convert Treg cells to T_H17 cells

CD38⁺ B cells interfere with the effects of AIT

Discussion

	Supported by grants from the National Nature and Science Foundation of China (32090052 and 81900914) and the Guangdong Provincial Key Laboratory of Regional Immunity and Diseases (2019B030301009).
	Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest.

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Vol 149 - N° 5

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CD38⁺ B cells affect immunotherapy for allergic rhinitis - 04/05/22

Abstract

Background

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Methods

Results

Conclusions

Plan

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