Multiplexed imaging of immune cells in staged multiple sclerosis lesions by mass cytometry.
Valeria RamagliaSalma Sheikh-MohamedKaren LeggCalvin ParkOlga L RojasStephanie ZandeeFred FuOlga OrnatskyEric C SwansonDavid PittAlexandre PratTrevor D McKeeJennifer L GommermanPublished in: eLife (2019)
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.
Keyphrases
- multiple sclerosis
- single cell
- rna seq
- white matter
- disease activity
- high resolution
- mass spectrometry
- spinal cord
- high throughput
- ms ms
- rheumatoid arthritis
- end stage renal disease
- systemic lupus erythematosus
- chronic kidney disease
- newly diagnosed
- rheumatoid arthritis patients
- ankylosing spondylitis
- ejection fraction
- peripheral blood
- inflammatory response
- prognostic factors
- stem cells
- neuropathic pain
- lipopolysaccharide induced
- mesenchymal stem cells
- quality improvement
- fluorescence imaging
- brain injury
- subarachnoid hemorrhage