IgG 3 + B cells are associated with the development of multiple sclerosis

Marsh‐Wakefield, F., Ashhurst, T., Trend, S., McGuire, H.M., Juillard, P., Zinger, A., Jones, A.P., Kermode, A.G., Hawke, S., Grau, G.E., Hart, P.H. and Byrne, S.N. (2020) IgG 3 + B cells are associated with the development of multiple sclerosis. Clinical & Translational Immunology, 9 (5).

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.

Item Type:	Journal Article
Murdoch Affiliation(s):	Institute for Immunology and Infectious Diseases
Publisher:	John Wiley & Sons Australia
Copyright:	© 2020 The Authors.
United Nations SDGs:	Goal 3: Good Health and Well-Being
URI:	http://researchrepository.murdoch.edu.au/id/eprint/55784

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