Decreased peripheral blood memory B cells are associated with the presence of interstitial lung disease in rheumatoid arthritis: a case-control study

Abstract

Objectives

Interstitial lung disease sometimes occurs in rheumatoid arthritis patients. Although the underlying immunological mechanisms responsible for interstitial lung disease associated with rheumatoid arthritis have not yet been clarified, some reports have suggested possible roles of B cells. To examine the role of B-cell subsets in interstitial lung disease in rheumatoid arthritis patients, we analyzed peripheral blood B-cell subsets.

Methods

We analyzed the frequencies of the peripheral blood B-cell subsets by flow cytometry in rheumatoid arthritis patients with and without interstitial lung disease (n = 16 and 81, respectively) and in healthy donors (n = 110) by high-resolution computed tomography.

Results

Compared with healthy donors, rheumatoid arthritis patients showed statistically higher frequencies of naive B cells and lower frequencies of memory B cells. Moreover, the frequencies of memory B cells were lower in rheumatoid arthritis patients with interstitial lung disease than in those without. Multivariate analysis showed that the frequency of memory B cells, particularly switched memory B cells, was significantly decreased in rheumatoid arthritis patients with interstitial lung disease, even after adjusting for prednisolone dose.

Conclusions

We suspect memory B cells play important roles in interstitial lung disease associated with rheumatoid arthritis.

Keywords:

• B cells
• flow cytometry
• interstitial lung disease
• peripheral blood
• rheumatoid arthritis

Acknowledgements

We thank the patients and healthy volunteers who participated in this research. We also thank all the members of the Department of Allergy and Rheumatology and the Department of Immunotherapy Management for the collection of clinical data.

Conflict of interest

Y. Nagafuchi received financial support or fees from Bristol-Myers Squibb, Chugai, Kissei, Mitsubishi Tanabe, and Pfizer. H. Harada received financial support or fees from Nihon Pharmaceutical and Novartis. S. Tateishi received consulting fees, speaking fees, and/or honoraria from Eisai, Maruho, AbbVie, and Eli Lilly. H. Kanda received consulting fees, speaking fees, and/or honoraria from Astellas, Abbvie, Ayumi, Asahi Kasei, Eisai, BMS, Pfizer, Daiichi-Sankyo, Janssen, Novartis, Nihon Kayaku, and Eli Lilly. S. Sumitomo received financial support or fees from AbbVie, Eisai, Chugai, UCB, Bristol-Myers Squibb, Takeda, AstraZeneca, Pfizer, Mitsubishi Tanabe, Novartis Pharma, Asahi Kasei, and Eli Lilly. H. Shoda receives fees from Pfizer, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Chugai, UCB, and Daiichi-Sankyo. K. Yamamoto received speaking fees from AbbVie, Astellas, AYUMI, Bristol-Myers Squibb, Chugai, Eisai, Janssen, Mitsubishi Tanabe, Ono, and UCB. K. Fujio has received grants, consulting fees, speaking fees, and/or honoraria from Takeda, Bristol-Myers Squibb, Mitsubishi Tanabe, Asahi Kasei, Sanofi, Eli Lilly, Daiichi-Sankyo, Ono, Janssen, AbbVie, Astellas, Eisai, Pfizer, Chugai, Novartis, UCB, Tsumura, Taisho Toyama, Nihon Kayaku, and Ayumi. All other authors declare no competing financial interest. The Department of Immunotherapy Management, Graduate School of Medicine, University of Tokyo had courses endowed by Mitsubishi Tanabe, Chugai, Ayumi, Taisho Toyama, Nippon Kayaku, UCB, and AbbVie.

Author contributions

TS, YN, HH, SS, HS, KY, and KF conceived, designed, and analyzed the experiments, and contributed to writing the manuscript. YN, YT, HT, and NH collected clinical data and performed the flow cytometric immunophenotyping experiments. ST and HK collected clinical data. TS and HH analyzed chest CT scans.

Additional information

Funding

This work was supported by the Ministry of Health, Labour and Welfare, Ministry of Education, Culture, Sports, Science and Technology KAKENHI Grant-in-Aid for Scientific Research (S) [grant number 23229007], Grant-in-Aid for Scientific Research (C) [grant number 26461462], Grant-in-Aid for challenging Exploratory Research [grant number 25670459] and the Japan Society for the Promotion of Science. This work was supported in part by grants from the Cell Science Research Foundation and Bristol-Myers Squibb (BMS).