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Immune phenotype changes in IgG4-related disease: CD161 + Treg and Foxp3 + Treg

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Abstract

Objective

We aimed to characterize the alterations in the immune phenotypes and explore the potential relevance to pathogenesis in IgG4-RD.

Methods

Forty-two IgG4-RD patients and thirty-eight healthy controls were recruited in this study. Peripheral immunocompetent cells including T cells, CD4 + T cells, CD8 + T cells, B cells, NK cells CD4 + CD45RA + T cells (naïve T cells), CD4 + CD25 − / + Foxp3 − T cells (Teff), CD4 + CD25hiCD127lowCD161 + T cells (CD161 + Treg), CD4 + CD25hiFoxp3 + T cells (Foxp3 + Treg), CD4 + CD4RA-CXCR5 + PD1 + CCR7low T cells (pTfh), T helper (Th) 1, Th2, and Th17 before and after treatment were immunophenotyped by flow cytometry.

Results

Compared with healthy controls, IgG4-RD patients showed higher proportions of NK (20.1% vs 13.6%, p < 0.01), Th1 (CD4 + IFN-γ + : 17.9% vs 14.2%, p = 0.061; TNF-α: 43.7% vs 36.7%, p < 0.05), Th2 (CD4 + IL-4 + : 2.4% vs 1.3%, p < 0.0001), CD161 + Treg (14.9% vs 11.6%, p < 0.01), pTfh (3.2% vs 2.4%, p < 0.05), and Foxp3 + Treg (8.3% vs 7.0%, p < 0.01) and lower proportions of B lymphocytes (8.4% vs 13.1%, p < 0.001), Teff (91.6% vs 92.6%, p < 0.01), and naïve Th cells (19.9% vs 32.1%, p < 0.01) before treatment. Foxp3 + Treg percentage decreased significantly after treatment (8.6% vs 6.9%, p < 0.05). Both serum C3 (r =  − 0.6374, p < 0.01) and C4 (r =  − 0.6174, p < 0.01) levels were in negative correlation with CD161 + Treg. The eosinophil percentage was positively correlated with Foxp3 + Treg (r = 0.5435, p < 0.05). Serum IgE level was positively correlated with Th2 (r = 0.5545, p < 0.05). There was a positive correlation between CD161 + Treg and pTfh (r = 0.4974, p < 0.05) while a negative correlation between Th2 and B cells (r =  − 0.4925, p < 0.05).

Conclusion

Immune phenotypes were altered in IgG4-RD. Treg/Teff balance was shifted toward Treg in IgG4-RD. CD161 + Treg was likely to be involved in the pathogenesis of IgG4-RD.

Key Points

•Immune phenotypes were altered in B cells, T cells, and NK cells in IgG4-RD.

•Treg/Teff balance was shifted toward Treg in IgG4-RD.

•CD161+ Treg maybe play a proinflammatory role in IgG4-RD

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Data availability

The data used to support the findings of this study are available from the corresponding author upon request.

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Funding

The work was supported by Capital’s Funds for Health Improvement and Research (No. 2022–2-2026) and National Natural Science Foundation of China (U1903210).

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Author notes

  1. Wenjie Bian, Yingni Li, and Feng Sun contributed equally to this work.

Authors and Affiliations

  1. Department of Rheumatology and Immunology, Peking University People’s Hospital, 11, Xizhimen South Street, Beijing, 100044, China

    Wenjie Bian, Yingni Li, Feng Sun, Xiaolin Sun, Ru Li, Jiangnan Fu, Yuxin Zhang, Shuang Chen & Yanying Liu

  2. Department of Clinical Laboratory, Peking University People’s Hospital, Beijing, 100044, China

    Changsheng Xia

  3. Department of Rheumatology and Immunology, Beijing Friendship Hospital, Capital Medical University, 95, Yongan Road, Beijing, 100050, China

    Yanying Liu

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  1. Wenjie Bian
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Bian, W., Li, Y., Sun, F. et al. Immune phenotype changes in IgG4-related disease: CD161 + Treg and Foxp3 + Treg. Clin Rheumatol 42, 1113–1124 (2023). https://doi.org/10.1007/s10067-022-06445-z

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