Publications by authors named "Chieh-Hsin Lee"

6 Publications

  • Page 1 of 1

Cross-sectional analysis of peripheral blood mononuclear cells in lymphopenic and non-lymphopenic relapsing-remitting multiple sclerosis patients treated with dimethyl fumarate.

Mult Scler Relat Disord 2021 Jul 7;52:103003. Epub 2021 May 7.

Division of Neurology, Department of Medicine, University of Alberta, Alberta Canada T6G 2M8, Edmonton, Canada. Electronic address:

Background: Relapsing-remitting multiple sclerosis (RRMS) is an autoimmune disorder of the central nervous system. Dimethyl Fumarate is a disease-modifying medication used to treat RRMS patients that can induce lymphopenia. We aimed to immunophenotype peripheral blood mononuclear cells (PBMC) in RRMS patients cross-sectionally and examine the characteristics and modifications of lymphopenia over time.

Methods: Characterization of PBMC was done by multiparametric flow cytometry. Patients had been on treatment for up to 4 years and were grouped into lymphopenic (DMF-L) and non-lymphopenic (DMF-N) patients.

Results: Lymphopenia affected the cell population changes over time, with other patient characteristics (gender, age, and previous treatment status) also having significant effects. In both lymphopenic and non-lymphopenic patients, PBMC percentages were reduced over time. While overall T and B cells frequencies were not affected, males, older patients and untreated patients had significant changes in B cell subpopulations over time. CD4 to CD8T cell ratio increased significantly in lymphopenic patients over time. CD4CD8T cell population was similarly reduced in both lymphopenic and non-lymphopenic patients, over time. While the monocyte and NK overall populations were not changed, non-classical monocyte subpopulation decreased over time in lymphopenic patients. We also found CD56CD16 and CD56CD16 NK cells frequencies changed over time in lymphopenic patients. Immune populations showed correlations with clinical outcomes measured by EDSS and relapse rate. Analysis of the overall immunophenotype showed that, while groups divided by other patient characteristics showed differences, the lymphopenia status overrode these differences, resulting in similar immunophenotype within DMF-L.

Conclusions: Our data provide evidence that under the same therapy, lymphopenia affects how the immunophenotype changes over time and can override the differences associated with other patient characteristics and possibly mask other significant changes in the immune profile of patients.
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http://dx.doi.org/10.1016/j.msard.2021.103003DOI Listing
July 2021

Multimodal peripheral fluid biomarker analysis in clinically isolated syndrome and early multiple sclerosis.

Mult Scler Relat Disord 2021 May 3;50:102809. Epub 2021 Feb 3.

Departments of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.

Background: Increasing evidence suggests that various inflammatory, immunological and metabolic pathways are altered in the clinically isolated syndrome (CIS) of multiple sclerosis (MS). Moreover, recent diagnostic criteria have made possible the very early diagnosis of MS. We evaluated multiple fluid biomarkers in people with early MS and CIS.

Methods: We measured blood levels of cytokines, matrix metalloproteinases (MMPs), serum metabolomics and immune cell immunophenotyping in participants in the Trial of Minocycline in a Clinically Isolated Syndrome of Multiple Sclerosis.

Results: When compared with healthy controls, people with early MS/CIS had higher levels of eotaxin, MCP-3, IL-1 receptor antagonist, IL-1β, IL-9 and IP-10, as well as MMPs 1, 8 and 9. In metabolomics analysis, the alanine, aspartate and glutamate metabolism and the synthesis and degradation of ketone bodies pathways were altered compared to healthy controls. There were no differences in lymphocyte subpopulation numbers. Out of all these biomarkers, only MMP-1 was able to differentiate between early MS and CIS, and was found to correlate with lesion volume and gadolinium enhancing lesions on MRI.

Conclusion: The immunological and metabolic profile of CIS and early MS is remarkably similar, supporting that these are a continuum of a common underlying pathophysiological process.
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http://dx.doi.org/10.1016/j.msard.2021.102809DOI Listing
May 2021

The Role of Inflammation in Depression and Fatigue.

Front Immunol 2019 19;10:1696. Epub 2019 Jul 19.

Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB, Canada.

Depression and fatigue are conditions responsible for heavy global societal burden, especially in patients already suffering from chronic diseases. These symptoms have been identified by those affected as some of the most disabling symptoms which affect the quality of life and productivity of the individual. While many factors play a role in the development of depression and fatigue, both have been associated with increased inflammatory activation of the immune system affecting both the periphery and the central nervous system (CNS). This is further supported by the well-described association between diseases that involve immune activation and these symptoms in autoimmune disorders, such as multiple sclerosis and immune system activation in response to infections, like sepsis. Treatments for depression also support this immunopsychiatric link. Antidepressants have been shown to decrease inflammation, while higher levels of baseline inflammation predict lower treatment efficacy for most treatments. Those patients with higher initial immune activation may on the other hand be more responsive to treatments targeting immune pathways, which have been found to be effective in treating depression and fatigue in some cases. These results show strong support for the hypothesis that depression and fatigue are associated with an increased activation of the immune system which may serve as a valid target for treatment. Further studies should focus on the pathways involved in these symptoms and the development of treatments that target those pathways will help us to better understand these conditions and devise more targeted treatments.
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http://dx.doi.org/10.3389/fimmu.2019.01696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6658985PMC
October 2020

Age-related cytokine effects on cancer-related fatigue and quality of life in acute myeloid leukemia.

J Geriatr Oncol 2020 04 10;11(3):402-409. Epub 2019 May 10.

Department of Psychiatry, University Health Network, Toronto, Canada.

Objectives: We determined whether cytokines are a potential target to improve cancer-related fatigue (CRF) and quality of life (QOL) in acute myeloid leukemia (AML).

Methods: 219 patients age 18+ undergoing intensive chemotherapy for AML were assessed at up to 4 time points (pre-treatment, 1 month, 6 months, 12 months). CRF and QOL were assessed with validated patient-reported outcome measures with minimum clinically important differences (MCID) of 4 and 10 points, respectively. A panel of 31 plasma cytokines was measured. CRF and QOL were regressed against scaled cytokine values, adjusting for age, gender, time, remission status, and hemoglobin in linear models.

Results: 498 cytokine samples were available. For CRF, the model R was 25.3%, with cytokines explaining 6.9% of the variance. For QOL, corresponding values were 27.9% and 7.4%, respectively. A shift from the 30th to 70th centile distribution of all cytokines was associated with an improvement in CRF by 5.2 points and a 10.2-point improvement in QOL. A shift from 5th to 95th centile in TNF-α but no other single cytokine was associated with a change of >MCID in CRF, but there was no similar association with QOL. Cytokines had greater explanatory power for CRF in older versus younger adults and the most influential cytokines differed by age, particularly TNF-α.

Conclusion: Cytokines explain a relatively small amount of CRF and QOL scores in patients with AML and effects differ by age group. For cytokine-targeted therapies to improve either outcome, multiple cytokines may need to be substantially altered and therapeutic targets may vary with age.
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http://dx.doi.org/10.1016/j.jgo.2019.04.009DOI Listing
April 2020

Symptom screening for constipation in oncology: getting to the bottom of the matter.

Support Care Cancer 2019 Jul 30;27(7):2463-2470. Epub 2018 Oct 30.

Department of Supportive Care, Princess Margaret Cancer Centre, University Health Network, 16th Floor, Room 749, 610 University Avenue, Toronto, ON, M5G 2M9, Canada.

Purpose: This study seeks to determine whether specific screening for constipation will increase the frequency of clinician response within the context of an established symptom screening program.

Methods: A "constipation" item was added to routine Edmonton Symptom Assessment System (ESAS) screening in gynecologic oncology clinics during a 7-week trial period, without additional constipation-specific training. Chart audits were then conducted to determine documentation of assessment and intervention for constipation in three groups of patients, those who completed (1) ESAS (n = 477), (2) ESAS-C with constipation (n = 435), and (3) no ESAS (n = 511).

Results: Among patients who were screened for constipation, 17% reported moderate to severe symptoms. Greater constipation severity increased the likelihood of documented assessment (Z = 2.37, p = .018) and intervention (Z = 1.99, p = .048). Overall rates of documented assessment were 36%, with the highest assessment rate in the no ESAS group (χ = 9.505, p = .006), a group with the highest proportion of late-stage disease. No difference in the rate of assessment was found between the ESAS and ESAS-C groups. Overall rates for documentation of intervention were low, and did not differ between groups.

Conclusions: Specific screening for constipation within an established screening program did not increase the documentation rate for constipation assessment or intervention. The inclusion of specific symptoms in multi-symptom screening initiatives should be carefully evaluated in terms of added value versus patient burden. Care pathways should include guidance on triaging results from multi-symptom screening, and clinicians should pay particular attention to patients who are missed from screening altogether, as they may be the most symptomatic group.
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http://dx.doi.org/10.1007/s00520-018-4520-7DOI Listing
July 2019

Characterization of lymphopenia in patients with MS treated with dimethyl fumarate and fingolimod.

Neurol Neuroimmunol Neuroinflamm 2018 Mar 28;5(2):e432. Epub 2017 Dec 28.

Division of Neurology, Department of Medicine, University of Alberta, Edmonton, Canada.

Objective: Lymphopenia is a common occurrence of disease-modifying therapies (DMTs) for relapsing-remitting MS (RRMS). The aim of this study was to dissect the prevalence of various lymphocyte subsets in patients with RRMS treated with 2 DMTs commonly associated with lymphopenia, dimethyl fumarate (DMF), and fingolimod (FTY).

Methods: Multicolor flow cytometry and multiplex assays were used to identify up to 50 lymphocyte subpopulations and to examine the expression of multiple cytokines in selected patients. We compared patients untreated (NT) or treated with FTY or DMF who did (DMF-L) or did not (DMF-N) develop lymphopenia.

Results: All FTY patients developed lymphopenia in both T-cell and B-cell compartments. CD41 T cells were more affected by this treatment than CD81 cells. In the B-cell compartment, the CD271IgD2 subpopulation was reduced. T cells but not B cells were significantly reduced in DMF-L. However, within the B cells, CD271 cells were significantly lower. Both CD41 and CD81 subpopulations were reduced in DMF-L. Within the remaining CD41 and CD81 compartments, there was an expansion of the naive subpopulation and a reduction of the effector memory subpopulation. Unactivated lymphocyte from DMF-L patients had significantly higher levels of interferon-γ, interleukin (IL)-12, IL-2, IL-4, IL-6, and IL-1β compared with DMF-N. In plasma, TNFβ was significantly higher in DMF-N and DMF-L compared with NT, whereas CCL17 was significantly higher in DMF-L compared with NT and DMF-N.

Conclusions: This study shows that different treatments can target different lymphocyte compartments and suggests that lymphopenia can induce compensatory mechanisms to maintain immune homeostasis.
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http://dx.doi.org/10.1212/NXI.0000000000000432DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5746425PMC
March 2018