A retrospective analysis of changes in lymphocyte levels in patients with multiple sclerosis during and after Tecfidera® treatment

Background There are currently no best practice recommendations for lymphocyte subset monitoring for patients with multiple sclerosis (pwMS) on disease-modifying therapies including Tecfidera® (dimethyl fumarate, DMF). However, there have been several cases of pwMS on DMF without severe lymphopenia who had high CD4:CD8 T cell ratios and went on to develop progressive multifocal leukoencephalopathy. Objective Our objective was to characterize the changes in immune profile during and after DMF treatment in pwMS. Methods A retrospective analysis of longitudinal data from 299 pwMS who have been treated with DMF at the Fraser Health Multiple Sclerosis Clinic in British Columbia, Canada. The blood test results were taken from January 1, 2013 to April 1, 2020. Results Our results suggest that CD8+ T cells had the highest proportional decrease compared to other lymphocyte subset populations and overall lymphocyte count in response to DMF treatment. CD56+ Natural Killer cells were similarly decreased in response to DMF treatment. CD4:CD8 T cell ratio was the measurement that had the highest rate of change in response to DMF initiation and discontinuation. Conclusion CD8+ T cell count and CD4:CD8 T cell ratio may be a more sensitive measurement of the immune landscape of patients with MS on DMF.

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High interindividual variability in the CD4/CD8 T cell ratio and natalizumab concentration levels in the cerebrospinal fluid of patients with multiple sclerosis

Clinical & Experimental Immunology ◽

10.1111/cei.12590 ◽

2015 ◽

Vol 180 (3) ◽

pp. 383-392 ◽

Cited By ~ 11

Author(s):

A. Harrer ◽

G. Pilz ◽

P. Wipfler ◽

K. Oppermann ◽

J. Sellner ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

T Cell ◽

Interindividual Variability ◽

Cd8 T Cell ◽

Cell Ratio ◽

High Interindividual Variability ◽

Concentration Levels

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The CD68+ Macrophages to CD8+ T-Cell Ratio Is Associated with Clinical Outcomes in Hepatocellular Carcinoma

SSRN Electronic Journal ◽

10.2139/ssrn.3449326 ◽

2019 ◽

Author(s):

Haibei Xin ◽

Huan Chen ◽

Hao Zhang ◽

Shanshan Li ◽

Zhang Minfeng ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

T Cell ◽

Clinical Outcomes ◽

Cd8 T Cell ◽

Cell Ratio

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Baseline CD4/CD8 T-Cell Ratio Predicts Prompt Immune Restoration Upon cART Initiation

Current HIV Research ◽

10.2174/1570162x14666160414111554 ◽

2016 ◽

Vol 14 (6) ◽

pp. 491-496 ◽

Cited By ~ 4

Author(s):

Francesco Bellissimo ◽

Marilia Rita Pinzone ◽

Benedetto Maurizio Celesia ◽

Bruno Cacopardo ◽

Giuseppe Nunnari

Keyword(s):

T Cell ◽

Cd8 T Cell ◽

Immune Restoration ◽

Cell Ratio ◽

Cart Initiation

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Corrigendum to “Inverted CD4 +/CD8+T cell ratio in Boran (Bos indicus) cattle” [Vet. Immunol. Immunopathol. 230 110126]

Veterinary Immunology and Immunopathology ◽

10.1016/j.vetimm.2021.110219 ◽

2021 ◽

pp. 110219

Author(s):

Maurine C. Makau ◽

Jessica Powell ◽

James Prendergast ◽

Perle Latré de Laté ◽

Liam J. Morrison ◽

...

Keyword(s):

T Cell ◽

Bos Indicus ◽

Cd8 T Cell ◽

Cell Ratio

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Lymphocyte subset analysis to evaluate the prognosis of HIV-negative patients with pneumocystis pneumonia

BMC Infectious Diseases ◽

10.1186/s12879-021-06124-5 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Fan Jin ◽

Jing Xie ◽

Huan-ling Wang

Keyword(s):

T Cell ◽

Cell Count ◽

Lymphocyte Subsets ◽

Nk Cell ◽

Cd8 T Cell ◽

Pneumocystis Pneumonia ◽

Lymphocyte Subset ◽

Cd4 T Cell ◽

Cell Counts ◽

Hiv Negative

Abstract Objectives We analysed the peripheral blood lymphocyte subsets of human immunodeficiency virus (HIV)-negative patients infected with pneumocystis pneumonia (PCP) to determine the relationships between the levels of different types of lymphocytes and the prognosis of patients. Methods We retrospectively reviewed HIV-negative patients with PCP diagnosed in our department. All the eligible patients underwent lymphocyte subset analysis on admission. Results A total of 88 HIV-negative PCP patients were enrolled in the study. In univariate analyses, low CD4+ T cell count, low CD8+ T cell count, and low natural killer cell (NK cell) count were associated with higher in-hospital mortality. CD8+ T cell count ≤300/μL was found to be an independent risk factor for poor prognosis in multivariate logistical regression analysis (p = 0.015, OR = 11.526, 95% CI = 1.597–83.158). Although low CD4+ T cell and NK cell counts were not independent risk factors, the mortality rates of PCP patients decreased as the CD4+ T cell and NK cell counts increased. Conclusion The immune process of Pneumocystis jirovecii infection is complex but important. We propose that lymphocyte subsets could give clinicians a better understanding of patient immune status, helping with the early identification of potentially lethal infections and treatment decision making, such as adjusting the immunosuppressive regimen and choosing an appropriate patient monitoring level.

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The CD8 T Cell in Multiple Sclerosis: Suppressor Cell Or Mediator of Neuropathology?

International Review of Neurobiology - The Neurobiology of Multiple Sclerosis ◽

10.1016/s0074-7742(07)79004-9 ◽

2007 ◽

pp. 73-97 ◽

Cited By ~ 38

Author(s):

Aaron J. Johnson ◽

Georgette L. Suidan ◽

Jeremiah McDole ◽

Istvan Pirko

Keyword(s):

Multiple Sclerosis ◽

T Cell ◽

Suppressor Cell ◽

Cd8 T Cell

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P073 Compartmentalised human gut immunity: studies of innate and adaptive lymphocyte distribution in the epithelium, lamina propria and GALT of healthy gut mucosa by flow cytometry

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.202 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S172-S172

Author(s):

A Carrasco Garcia ◽

A Rao ◽

E Kokkinou ◽

S Haapaniemi ◽

U Lindforss ◽

...

Keyword(s):

Flow Cytometry ◽

T Cell ◽

Lamina Propria ◽

Immune Cell ◽

Cd8 T Cell ◽

Peyer's Patches ◽

Peyer’S Patches ◽

Human Gut ◽

Cell Ratio ◽

Health And Disease

Abstract Background The human gut mucosal immune system is compartmentalised in distinct and specialised immune niches. The epithelium and the lamina propria have been proposed as effector sites, while gut-associated lymphoid tissues (GALTs) constitute inductive immune niches. The major mucosal GALTs are the Peyer’s patches in the ileum and the colonic isolated lymphoid follicles (ILFs), scattered in the submucosa of the colon. The majority of studies of human gut immune function in health and disease have analysed unfractionated mucosal tissue samples. Hence, in contrast to mice, little is known about compartmentalised immune cell specialisation in the human gut. The aim of this study was to use novel dissection methods to analyse separate human gut immune niches. Methods Macroscopically healthy margins from colorectal cancer colectomies were obtained at a minimum distance of 10 cm from the tumour border. After faeces, mucus, fat and muscle removal, Peyer’s patches were identified and dissected using a stereomicroscope (based on Keita et al., Lab Invest, 2006). Colonic mucosa and submucosa (containing ILFs) fractions were mechanically separated by forceps (based on the method developed by Fenton et al., Immunity, under revision). Isolation of epithelial and lamina propria fractions from the mucosal compartment was performed by calcium chelation (DTT and EDTA) and enzymatic digestion (Collagenase II and DNAse), respectively. Cell suspensions from each fraction were analysed by flow cytometry (BD LSR-Fortessa and BD FACSymphony). Results As expected, mucosal GALTs were characterised by an enrichment of germinal centre B cells (CD19+CD20+CD38+), lymphoid tissue-like innate lymphoid cells (Lin−CD127+CD117+Nrp1+) and a higher CD4+/CD8+ T-cell ratio vs. mucosa, whereas the mucosal fraction was enriched for plasma cells (CD19+CD20−CD38high) and distinguished by a decreased CD4+/CD8+ T-cell ratio as compared with the GALT in both ileum and colon. CD19+/CD3+ ratios were only higher in Peyer’s patches but not in colonic submucosa enriched with ILFs, possibly due to the smaller size of the B-cell follicles in the latter. The intraepithelial compartment lacked B cells and contained more γδ-T cells as compared with the GALT and lamina propria. Conclusion We have used novel dissection methods in human intestinal tissues that reveal a compartmentalised immune cell specialisation that is in line with what has previously been described in mice. The method will allow for future deeper analysis of the human gut immune niches in health and disease, such as in inflammatory bowel disease.

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