Multiple Sclerosis (MS) is characterized by demyelinated and inflammatory lesions in the brain and spinal cord that are highly variable in terms of cellular content. Here we used imaging mass cytometry (IMC) to enable the simultaneous imaging of 15+ proteins within staged MS lesions. To test the potential for IMC to discriminate between different types of lesions, we selected a case with severe rebound MS disease activity after natalizumab cessation. With post-acquisition analysis pipelines we were able to: (1) Discriminate demyelinating macrophages from the resident microglial pool; (2) Determine which types of lymphocytes reside closest to blood vessels; (3) Identify multiple subsets of T and B cells, and (4) Ascertain dynamics of T cell phenotypes vis-à-vis lesion type and location. We propose that IMC will enable a comprehensive analysis of single-cell phenotypes, their functional states and cell-cell interactions in relation to lesion morphometry and demyelinating activity in MS patients.
All data generated and analysed during this study are included in the manuscript and supporting files. Source data file has been provided for Figure 7.
- Valeria Ramaglia
- Jennifer L Gommerman
- Alexandre Prat
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Human subjects: This work included the use of post-mortem brain tissue. Written consent for post-mortem donation of the CNS to research from the MS donor was obtained (ethics committee approval number BH.07.001).Ethical approval for the use of post-mortem brain tissue from the control donor of the Netherlands Brain Bank was obtained (VU Medical Center ethic committee approval Reference number 2009/148)
- Isaac M Chiu, Harvard Medical School, United States
© 2019, Ramaglia et al.
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