Causal role of immune cells in chronic obstructive pulmonary disease: Mendelian randomization study

ABSTRACT

Objectives

Innate and adaptive immunity play different roles in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, previous studies on the relationship between immune cells and COPD reported inconsistent results.

Methods

The causal connection between 731 immune cells and COPD was established using a two-sample Mendelian randomization (MR) analysis through publicly accessible genetic data. The heterogeneity and horizontal pleiotropism of the findings were confirmed using sensitivity analysis.

Results

In the B-cell panel, B-cell activating factor receptor (BAFF-R) on CD20⁻ and CD20 on IgD⁻CD38^bright (OR (95% CI): 0.93 (0.88, 0.99) and 0.97 (0.95, 0.98), respectively) were discovered to be protective. In the cDC panel, CD62L⁻ plasmacytoid DC AC, CD80 on monocytes and CD11c on myeloid DCs (OR (95% CI): 0.94 (0.92, 0.97), 0.97 (0.94, 0.99) and (0.97 (0.95, 0.98), respectively) exerted protective effects. However, unswitched memory AC (OR (95%CI): 1.08 (1.01,1.15)) and CD 19 on IgD⁻ CD 27⁻ (OR (95%CI): 1.06 (1.02,1.10)) were hazardous in the B-cell panel. However, among the 731 immune cell phenotypes, no causal relationship was found for COPD on immune cells.

Conclusion

This study found a potential causal relationship between immune cells in COPD, ruling out reverse causation. This study provides new avenues for studying the mechanisms of COPD.

KEYWORDS:

• Chronic obstructive pulmonary disease
• immunity
• Mendelian randomization
• causal inference
• genetic variation

Article highlights

• Mendelian randomization was used to analyze the causal relationship between 731 immune cell phenotypes and the risk of COPD.

• Of the seven panels, only B cells and dendritic cells had a causal relationship to the risk of COPD.

• Two phenotypes in the B cell panel were discovered to be protective: BAFF-R on CD20⁻ and CD20 on IgD⁻CD38^bright.

• Unsw mem AC and CD 19 on IgD⁻CD27⁻ were hazardous in the B-cell panel.

• In the cDC panel, three immune cell phenotypes decreased as the risk of COPD increased: CD62L⁻ plasmacytoid DC AC, CD 80 on monocyte-derived DCs and CD11c on myeloid DCs.

• COPD have no causal relationship to immune cells.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have received an honorarium from Expert Opinion on Drug Metabolism and Toxicology for their review work but have no other relevant financial relationships to disclose. Peer reviewers on this manuscript have no other relevant financial or other relationships to disclose.

Availability of data and materials

All data included in this study are available upon request through contact with the corresponding author.

Author contributions

B Ran and J Qin: Planning the study. B Ran: Analysis of the data. B Ran and J Qin: drafting. Y Wu and F Wen: Revision of the article. All authors critically reviewed the manuscript, provided important intellectual input, approved the final version, and agree to be accountable for their contributions. All the authors have read and approved the final manuscript.

Acknowledgments

We express our gratitude to the 1•3•5 Excellent Discipline Project of West China Hospital at Sichuan University (ZYJC18012, ZYGD23009) and the National Natural Science Foundation of China (82100047) for their financial support.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/1744666X.2023.2295987.

Additional information

Funding

This work was supported by the 1•3•5 Project for Disciplines of Excellence, West China Hospital of Sichuan University (ZYJC18012, ZYGD23009) and the National Natural Science Foundation of China [82100047]. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.