Clinical & Translational Immunology (Jan 2020)

IgG3+ B cells are associated with the development of multiple sclerosis

  • Felix Marsh‐Wakefield,
  • Thomas Ashhurst,
  • Stephanie Trend,
  • Helen M McGuire,
  • Pierre Juillard,
  • Anna Zinger,
  • Anderson P Jones,
  • Allan G Kermode,
  • Simon Hawke,
  • Georges E Grau,
  • Prue H Hart,
  • Scott N Byrne

DOI
https://doi.org/10.1002/cti2.1133
Journal volume & issue
Vol. 9, no. 5
pp. n/a – n/a

Abstract

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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.

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