Decision letter: Multiplexed imaging of immune cells in staged multiple sclerosis lesions by mass cytometry

ABSTRACTMultiple Sclerosis (MS) is characterized by demyelinated and inflammatory lesions in the brain and spinal cord. Lesions contain immune cells with variable phenotypes and functions. Here we use imaging mass cytometry (IMC) to enable the simultaneous imaging of 15+ proteins within 11 staged MS lesions. Using this approach, we demonstrated that the majority of demyelinating macrophage-like cells in active lesions were derived from the resident microglial pool. Although CD8+ T cells predominantly infiltrated the lesions, CD4+ T cells were also abundant but localized closer to blood vessels. B cells with a predominant switched memory phenotype were enriched across all lesion stages and were found to preferentially infiltrate the tissue as compared to unswitched B cells which localized to the vasculature. 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 the MS brain.

Download Full-text

Author response: Multiplexed imaging of immune cells in staged multiple sclerosis lesions by mass cytometry

10.7554/elife.48051.028 ◽

2019 ◽

Author(s):

Valeria Ramaglia ◽

Salma Sheikh-Mohamed ◽

Karen Legg ◽

Calvin Park ◽

Olga L Rojas ◽

...

Keyword(s):

Multiple Sclerosis ◽

Immune Cells ◽

Author Response ◽

Mass Cytometry ◽

Multiplexed Imaging

Download Full-text

Multiplexed imaging of immune cells in staged multiple sclerosis lesions by mass cytometry

eLife ◽

10.7554/elife.48051 ◽

2019 ◽

Vol 8 ◽

Cited By ~ 10

Author(s):

Valeria Ramaglia ◽

Salma Sheikh-Mohamed ◽

Karen Legg ◽

Calvin Park ◽

Olga L Rojas ◽

...

Keyword(s):

Multiple Sclerosis ◽

Mass Cytometry ◽

Simultaneous Imaging ◽

Lesion Type ◽

Multiplexed Imaging ◽

Functional States ◽

T Cell Phenotypes ◽

Cell Phenotypes ◽

Brain And Spinal Cord ◽

The Brain

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.

Download Full-text

Author response for "Mass cytometry analysis of blood immune cells from psoriasis patients on biological therapy"

10.1002/eji.202048857/v2/response1 ◽

2020 ◽

Author(s):

SM Solberg ◽

AK Aarebrot ◽

I Sarkar ◽

A Petrovic ◽

LF Sandvik ◽

...

Keyword(s):

Immune Cells ◽

Biological Therapy ◽

Author Response ◽

Mass Cytometry

Download Full-text

Faculty Opinions recommendation of Highly multiplexed imaging of tumor tissues with subcellular resolution by mass cytometry.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718293838.793492686 ◽

2014 ◽

Author(s):

Andreas Grützkau

Keyword(s):

Mass Cytometry ◽

Tumor Tissues ◽

Multiplexed Imaging ◽

Subcellular Resolution

Download Full-text

Expression of CYP24A1 and other multiple sclerosis risk genes in peripheral blood indicates response to vitamin D in homeostatic and inflammatory conditions

Genes and Immunity ◽

10.1038/s41435-021-00144-6 ◽

2021 ◽

Author(s):

Samantha P. L. Law ◽

Prudence N. Gatt ◽

Stephen D. Schibeci ◽

Fiona C. McKay ◽

Steve Vucic ◽

...

Keyword(s):

Multiple Sclerosis ◽

Vitamin D ◽

Immune Cells ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Immunological Response ◽

Response To Treatment ◽

Peripheral Blood Mononuclear ◽

Risk Genes ◽

Inflammatory Models

AbstractAlthough genetic and epidemiological evidence indicates vitamin D insufficiency contributes to multiple sclerosis (MS), and serum levels of vitamin D increase on treatment with cholecalciferol, recent metanalyses indicate that this vitamin D form does not ameliorate disease. Genetic variation in genes regulating vitamin D, and regulated by vitamin D, affect MS risk. We evaluated if the expression of vitamin D responsive MS risk genes could be used to assess vitamin D response in immune cells. Peripheral blood mononuclear cells (PBMCs) were isolated from healthy controls and people with MS treated with dimethyl fumarate. We assayed changes in expression of vitamin D responsive MS risk (VDRMS) genes in response to treatment with 25 hydroxy vitamin D in the presence or absence of inflammatory stimuli. Expression of CYP24A1 and other VDRMS genes was significantly altered in PBMCs treated with vitamin D in the homeostatic and inflammatory models. Gene expression in MS samples had similar responses to controls, but lower initial expression of the risk genes. Vitamin D treatment abrogated these differences. Expression of CYP24A1 and other MS risk genes in blood immune cells indicate vitamin D response and could enable assessment of immunological response to vitamin D in clinical trials and on therapy.

Download Full-text

Understanding the tumour immune microenvironment of stage III colorectal cancer using multiplexed imaging mass cytometry

Pathology ◽

10.1016/j.pathol.2021.06.063 ◽

2021 ◽

Vol 53 ◽

pp. S36-S37

Author(s):

Minh Tran ◽

Andrew Su ◽

HoJoon Lee ◽

Richard Cruz ◽

Lance Pflieger ◽

...

Keyword(s):

Colorectal Cancer ◽

Stage Iii ◽

Mass Cytometry ◽

Immune Microenvironment ◽

Multiplexed Imaging

Download Full-text

Simultaneous Multiplexed Imaging of mRNA and Proteins with Subcellular Resolution in Breast Cancer Tissue Samples by Mass Cytometry

Cell Systems ◽

10.1016/j.cels.2018.04.004 ◽

2018 ◽

Vol 6 (4) ◽

pp. 531 ◽

Cited By ~ 29

Author(s):

Daniel Schulz ◽

Vito Riccardo Tomaso Zanotelli ◽

Jana Raja Fischer ◽

Denis Schapiro ◽

Stefanie Engler ◽

...

Keyword(s):

Breast Cancer ◽

Breast Cancer Tissue ◽

Cancer Tissue ◽

Mass Cytometry ◽

Tissue Samples ◽

Multiplexed Imaging ◽

Subcellular Resolution

Download Full-text

Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility

Science ◽

10.1126/science.aav7188 ◽

2019 ◽

Vol 365 (6460) ◽

pp. eaav7188 ◽

Cited By ~ 122

Author(s):

Keyword(s):

Multiple Sclerosis ◽

Immune Cells ◽

Expression Profiles ◽

Human Microglia ◽

Histocompatibility Complex ◽

The Central Nervous System ◽

Reference Map ◽

Peripheral Immune Cells ◽

Genomic Map ◽

Cellular Components

We analyzed genetic data of 47,429 multiple sclerosis (MS) and 68,374 control subjects and established a reference map of the genetic architecture of MS that includes 200 autosomal susceptibility variants outside the major histocompatibility complex (MHC), one chromosome X variant, and 32 variants within the extended MHC. We used an ensemble of methods to prioritize 551 putative susceptibility genes that implicate multiple innate and adaptive pathways distributed across the cellular components of the immune system. Using expression profiles from purified human microglia, we observed enrichment for MS genes in these brain-resident immune cells, suggesting that these may have a role in targeting an autoimmune process to the central nervous system, although MS is most likely initially triggered by perturbation of peripheral immune responses.

Download Full-text

Fatal COVID-19 in an MS patient on natalizumab: A case report

Multiple Sclerosis Journal - Experimental Translational and Clinical ◽

10.1177/2055217320942931 ◽

2020 ◽

Vol 6 (3) ◽

pp. 205521732094293

Author(s):

Kathryn Rimmer ◽

Rebecca Farber ◽

Kiran Thakur ◽

Genna Braverman ◽

Dina Podolsky ◽

...

Keyword(s):

Multiple Sclerosis ◽

Immune Cells ◽

African American Woman ◽

Fatal Case ◽

American Woman ◽

Multiple Risk Factors ◽

Natalizumab Treatment ◽

Obesity Hypertension ◽

Multiple Sclerosis Patients ◽

Peripheral Immune Cells

We report a fatal case of COVID-19 in a 51-year-old African American woman with multiple sclerosis on natalizumab. She had multiple risk factors for severe COVID-19 disease including race, obesity, hypertension, and elevated inflammatory markers, but the contribution of natalizumab to her poor outcome remains unknown. We consider whether altered dynamics of peripheral immune cells in the context of natalizumab treatment could worsen the cytokine storm syndrome associated with severe COVID-19. We discuss extended interval dosing as a risk-reduction strategy for multiple sclerosis patients on natalizumab, and the use of interleukin-6 inhibitors in such patients who contract COVID-19.

Download Full-text