A study of 51 subtypes of peripheral blood immune cells in newly diagnosed young type 1 diabetes patients

Oras, Astrid; Peet, Aleksandr; Giese, Thomas; Tillmann, Vallo; Uibo, Raivo

doi:10.1111/cei.13332

Cited by 36 publications

(47 citation statements)

References 47 publications

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“…Alterations within CD19 + B cell subsets were only found in patients with HT despite that autoantibodies are also present in T1D, GD and AD. Previous studies addressing peripheral B cells in T1D and GD have reported that frequencies were similar compared to HC (32)(33)(34) or that functional responses toward autoantigens were changed (35,36).…”

Section: Discussionmentioning

confidence: 95%

“…Most studies addressing NK cells in T1D have focused on their cytotoxic function, whereas studies investigating the phenotype of cell subsets are limited (52,53). It has been recently shown that children with newly diagnosed T1D had reduced frequencies of CD16 + CD56 dim and CD16 − CD56 dim NK cell subsets than HC (32). We have previously reported that multiple autoantibody-positive children, who later progressed to T1D, had higher frequencies of two CD8 + CD16 + CD56 dim NK cell subsets than autoantibody-negative individuals (18).…”

Section: Discussionmentioning

confidence: 99%

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Mass Cytometry Studies of Patients With Autoimmune Endocrine Diseases Reveal Distinct Disease-Specific Alterations in Immune Cell Subsets

et al. 2020

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Although there is evidence that autoimmune diseases share similar immunogenetic mechanisms, studies comparing peripheral CD45 + cells from patients with autoimmune endocrine diseases in parallel are limited. In this study, we applied high-dimensional single-cell mass cytometry to phenotypically characterize PBMC from patients with new-onset (N-T1D) and long-standing type 1 diabetes, Hashimoto's thyroiditis (HT), Graves' disease and autoimmune Addison's disease (AD), as well as healthy controls. The frequency of CD20 lo CD27 hi CD38 hi HLA-DR int plasmablasts, CD86 + CD14 lo CD16 + non-classical monocytes and two subsets of CD56 dim HLA-DR + IFN-γ + NK cells were increased in patients with HT. Subsets of CD56 dim CD69 + HLA-DR − NK cells and CD8 + TEMRA cells, both expressing IFN-γ, were expanded and reduced, respectively, in the N-T1D group. In addition, patients with AD were characterized by an increased percentage of central memory CD8 + T cells that expressed CCR4, GATA3, and IL-2. We demonstrate that patients with N-T1D, HT, and AD had altered frequencies of distinct subsets within antigen-presenting and cytotoxic cell lineages. Previously unreported alterations of specific cell subsets were identified in samples from patients with HT and AD. Our study might contribute to a better understanding of shared and diverging immunological features between autoimmune endocrine diseases.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Mass Cytometry Studies of Patients With Autoimmune Endocrine Diseases Reveal Distinct Disease-Specific Alterations in Immune Cell Subsets

et al. 2020

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“…Many studies have described how T1D development is associated with changes in various peripheral blood circulating cell populations, and their asset might be associated with clinical and age-related differences in T1D patients [13][14][15][16]. It has been shown that in T1D subjects, the number of natural killer (NK), dendritic (DC), and T cell subsets is significantly altered compared to controls [17]. Moreover, the immunological profile significantly changes over time in T1D, and a specific peripheral immune cell signature can be associated with worsening disease [18].…”

Section: Introductionmentioning

confidence: 99%

Blood Co-Circulating Extracellular microRNAs and Immune Cell Subsets Associate with Type 1 Diabetes Severity

Garavelli

Bruzzaniti

Tagliabue

et al. 2020

IJMS

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Immune cell subsets and microRNAs have been independently proposed as type 1 diabetes (T1D) diagnostic and/or prognostic biomarkers. Here, we aimed to analyze the relationships between peripheral blood circulating immune cell subsets, plasmatic microRNAs, and T1D. Blood samples were obtained from both children with T1D at diagnosis and age-sex matched healthy controls. Then, immunophenotype assessed by flow cytometry was coupled with the quantification of 60 plasmatic microRNAs by quantitative RT-PCR. The associations between immune cell frequency, plasmatic microRNAs, and the parameters of pancreatic loss, glycemic control, and diabetic ketoacidosis were assessed by logistic regression models and correlation analyses. We found that the increase in specific plasmatic microRNAs was associated with T1D disease onset (let-7c-5p, let-7d-5p, let-7f-5p, let-7i-5p, miR-146a-5p, miR-423-3p, and miR-423-5p), serum C-peptide concentration (miR-142-5p and miR-29c-3p), glycated hemoglobin (miR-26a-5p and miR-223-3p) and the presence of ketoacidosis (miR-29c-3p) more strongly than the evaluated immune cell subset frequency. Some of these plasmatic microRNAs were shown to positively correlate with numbers of blood circulating B lymphocytes (miR-142-5p) and CD4+CD45RO+ (miR-146a-5p and miR-223-3p) and CD4+CD25+ cells (miR-423-3p and miR-223-3p) in children with T1D but not in healthy controls, suggesting a disease-specific microRNA association with immune dysregulation in T1D. In conclusion, our results suggest that, while blood co-circulating extracellular microRNAs and immune cell subsets may be biologically linked, microRNAs may better provide powerful information about T1D onset and severity.

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“…A recent study that examined a variety of immune cell subsets and cellular molecules in newly diagnosed children with T1DM found that the level of memory-regulatory T cells (mTreg) decreased after the appearance of clinical symptoms and aTreg and Th17 cells were significantly elevated in the first year of onset (the remission phase often occur) (15). The mTregs were also noted to be positively correlated with C-peptide in T1DM patients (16). Evidence of the obvious dynamic changes in Tregs in the different stages of remission phase suggested that the immune response during the remission phase was most likely related to the frequency and function of Tregs.…”

Section: Immune Cellsmentioning

confidence: 99%

“…The number of mononuclear cells also decreased after the onset of T1DM and reached the nadir in the first year (15). These changes of the immune cells in peripheral blood suggest an active extravasation to target tissues, probably contributing to the downregulation of the autoimmune response (16).…”

Section: Immune Cellsmentioning

confidence: 99%

The Remission Phase in Type 1 Diabetes: Role of Hyperglycemia Rectification in Immune Modulation

Tang

Zhong

et al. 2019

Front. Endocrinol.

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The remission phase (or honeymoon period) is a spontaneous “temporary cure stage” in type 1 diabetes course, which provides a good human model for studying β-cell protection. The exact mechanisms are still uncertain, but one of the generally recognized mechanisms is that correction of “glucotoxicity” by exogenous insulin therapy leads to “β-cell rest” and β-cell recovery. Beyond this, the remission phase is accompanied by changes in various immune cells and immune molecules, indicating downregulation of immune response, and induction of immune tolerance. The role of hyperglycemia rectification in the regulation of immune response should be emphasized because glucose metabolism is critical to maintain the normal function of immune system. Here, recent evidence of immune modulation based on the rectification of hyperglycemia from multiple aspects such as immune cells, inflammatory cytokines, biomolecules, and cell antigenicity was reviewed. It should be noteworthy that the interaction between glucose metabolism and immune plays an important role in the pathogenesis of the remission phase. The best intervention strategy may be the combination of strict glycemic control and immune modulation to protect β-cell function as early as possible.

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A study of 51 subtypes of peripheral blood immune cells in newly diagnosed young type 1 diabetes patients

Cited by 36 publications

References 47 publications

Mass Cytometry Studies of Patients With Autoimmune Endocrine Diseases Reveal Distinct Disease-Specific Alterations in Immune Cell Subsets

Mass Cytometry Studies of Patients With Autoimmune Endocrine Diseases Reveal Distinct Disease-Specific Alterations in Immune Cell Subsets

Blood Co-Circulating Extracellular microRNAs and Immune Cell Subsets Associate with Type 1 Diabetes Severity

The Remission Phase in Type 1 Diabetes: Role of Hyperglycemia Rectification in Immune Modulation

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