# Immunophenotyping of Patients With Rheumatoid Arthritis Reveals Difference in CD27+IgD+ Unswitched Memory B Cell Profiles

**Authors:** Bérénice Hansen, Raul Da Costa, Dominique Revets, Fanny Hedin, Maria Konstantinou, Eduardo Rosales Jubal, Franck Ngangom, Cédric C. Laczny, Kirsten Roomp, Viacheslav Petrov, Andreas Michalsen, Etienne Hanslian, Daniela A. Koppold, Anika Rajput Khokhar, Nico Steckhan, Michael Jeitler, Brit Mollenhauer, Sebastian Schade, Michel Vaillant, Antonio Cosma, Paul Wilmes, Jochen G. Schneider

PMC · DOI: 10.1155/mi/9675331 · Mediators of Inflammation · 2025-07-29

## TL;DR

This study finds that patients with rheumatoid arthritis have fewer specific memory B cells compared to healthy individuals.

## Contribution

The study identifies for the first time a significant reduction in CD27+IgD+ unswitched memory B cells in rheumatoid arthritis patients.

## Key findings

- RA patients have significantly fewer CD27+IgD+ unswitched memory B cells compared to healthy controls.
- The reduction in these cells is the only significant immune profile difference observed in RA patients.

## Abstract

Objectives: Over the past decades, the prevalence of noncommunicable diseases has surged significantly, including the systemic autoimmune disorder rheumatoid arthritis (RA). Despite extensive research and advancement of RA therapy, effective prevention strategies or cures remain elusive, and the mechanisms underlying RA pathogenesis unclear. It is crucial to gain deeper insights into RA pathophysiology. The objective of this study is to provide a comprehensive immunophenotyping of patients with RA.

Methods: We generated and analyzed deep immunophenotyping data from 52 patients with RA and 47 healthy controls (HCs). Whole blood samples were stained with extracellular markers, and intracellular antibodies and analyzed for 32 different cell markers using mass cytometry by time of flight. The acquired data was analyzed by both manual and automatic unsupervised tools and subsequently complemented with anthropometric data and clinical-laboratory parameters.

Results: We observed a significant disparity in immune cell profiles between patients with RA and HC, notably a reduced frequency of CD27+IgD+ unswitched memory B (mB) cells in patients with RA (p-value < 0.01), with the disease RA being the primary and only significant factor explaining up to 17.9% of the variance of these cells.

Conclusion: Our results reveal, for the first time, that a reduced frequency of unswitched mB cells in patients with RA is the only significant abnormality distinguishing patients with RA from HC in a complex immunophenotyping panel of 72 different cell populations. This provides important information to further individualize various interventions and possibly help to design novel therapeutic interventions.

## Linked entities

- **Proteins:** CD27 (CD27 molecule), Igd (immunoglobulin delta heavy chain constant region)
- **Diseases:** rheumatoid arthritis (MONDO:0008383)

## Full-text entities

- **Genes:** ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, FOXP3 (forkhead box P3) [NCBI Gene 50943] {aka AIID, DIETER, IPEX, JM2, PIDX, XPID}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, CD19 (CD19 molecule) [NCBI Gene 930] {aka B4, CVID3}, PTPRC (protein tyrosine phosphatase receptor type C) [NCBI Gene 5788] {aka B220, CD45, CD45R, GP180, IMD105, L-CA}, CDAN1 (codanin 1) [NCBI Gene 146059] {aka CDA1, CDAI, CDAN1A, DLT, PRO1295}, CD27 (CD27 molecule) [NCBI Gene 939] {aka S152, S152. LPFS2, T14, TNFRSF7, Tp55}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}
- **Diseases:** rheumatoid factor (MESH:D001171), depression (MESH:D003866), fatigue (MESH:D005221), anxiety (MESH:D001007), polyarthritis (MESH:D001168), RA (MESH:D001172), sleep disturbance (MESH:D012893), autoimmune disease (MESH:D001327), sarcopenia (MESH:D055948), cytotoxicity (MESH:D064420), chronic inflammation (MESH:D007249), SLE (MESH:D008180), breathing disorders (MESH:D012891), Sjogren's syndrome (MESH:D012859), HC (MESH:D000067329), joint destruction (MESH:D008105), joint pain (MESH:D018771)
- **Chemicals:** Leflunomide (MESH:D000077339), heparin (MESH:D006493), methotrexate (MESH:D008727), Creatinine (MESH:D003404), Golimumab (MESH:C529000), Tocilizumab (MESH:C502936), Formaldehyde (MESH:D005557), CyTOF (-), Baricitinib (MESH:C000596027), Prednisolone (MESH:D011239), cholesterol (MESH:D002784), glucose (MESH:D005947), Adalimumab (MESH:D000068879), Sulfasalazine (MESH:D012460), Sarilumab (MESH:C000592401), water (MESH:D014867)
- **Species:** gut metagenome (species) [taxon 749906], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** mB — Opodiphthera eucalypti (Emperor gum moth), Spontaneously immortalized cell line (CVCL_C2VY)

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12324914/full.md

## References

41 references — full list in the complete paper: https://tomesphere.com/paper/PMC12324914/full.md

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Source: https://tomesphere.com/paper/PMC12324914