Journal article
IgG 3 + B cells are associated with the development of multiple sclerosis
Clinical & Translational Immunology, Vol.9(5)
2020
Abstract
Objectives
Disease‐modifying therapies (DMTs) targeting B cells are amongst the most effective for preventing multiple sclerosis (MS) progression. IgG3 antibodies and their uncharacterised B‐cell clones are predicted to play a pathogenic role in MS. Identifying subsets of IgG3+ B cells involved in MS progression could improve diagnosis, could inform timely disease intervention and may lead to new DMTs that target B cells more specifically.
Methods
We designed a 31‐parameter B‐cell‐focused mass cytometry panel to interrogate the role of peripheral blood IgG3+ B cells in MS progression of two different patient cohorts: one to investigate the B‐cell subsets involved in conversion from clinically isolated syndrome (CIS) to MS; and another to compare MS patients with inactive or active stages of disease. Each independent cohort included a group of non‐MS controls.
Results
Nine distinct CD20+IgD−IgG3+ B‐cell subsets were identified. Significant changes in the proportion of CD21+CD24+CD27−CD38− and CD27+CD38hiCD71hi memory B‐cell subsets correlated with changes in serum IgG3 levels and time to conversion from CIS to MS. The same CD38− double‐negative B‐cell subset was significantly elevated in MS patients with active forms of the disease. A third CD21+CD24+CD27+CD38− subset was elevated in patients with active MS, whilst narrowband UVB significantly reduced the proportion of this switched‐memory B‐cell subset.
Conclusion
We have identified previously uncharacterised subsets of IgG3+ B cells and shown them to correlate with autoimmune attacks on the central nervous system (CNS). These results highlight the potential for therapies that specifically target IgG3+ B cells to impact MS progression.
Details
- Title
- IgG 3 + B cells are associated with the development of multiple sclerosis
- Authors/Creators
- F. Marsh‐Wakefield (Author/Creator)T. Ashhurst (Author/Creator) - The University of SydneyS. Trend (Author/Creator) - The Kids Research Institute AustraliaH.M. McGuire (Author/Creator) - The University of SydneyP. Juillard (Author/Creator) - The University of SydneyA. Zinger (Author/Creator) - The University of SydneyA.P. Jones (Author/Creator) - The Kids Research Institute AustraliaA.G. Kermode (Author/Creator) - Perron Institute for Neurological and Translational ScienceS. Hawke (Author/Creator) - The University of SydneyG.E. Grau (Author/Creator) - The University of SydneyP.H. Hart (Author/Creator) - The Kids Research Institute AustraliaS.N. Byrne (Author/Creator) - The University of Sydney
- Publication Details
- Clinical & Translational Immunology, Vol.9(5)
- Publisher
- John Wiley & Sons Australia
- Identifiers
- 991005544708107891
- Copyright
- © 2020 The Authors.
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.203 Neuromuscular Disorders
- 1.203.147 Multiple Sclerosis
- Web Of Science research areas
- Immunology
- ESI research areas
- Immunology