Immune cell and cytokine patterns in children with type 1 diabetes mellitus undergoing a remission phase: A longitudinal study

Fitas, Ana Laura; Martins, Catarina; Borrego, Luís Miguel; Lopes, Lurdes; Jörns, Anne; Lenzen, Sigurd; Limbert, Catarina

doi:10.1111/pedi.12671

Cited by 21 publications

(33 citation statements)

References 49 publications

(60 reference statements)

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“…2). honeymoon phase) [25]. In addition, C-peptide correlated positively with slan -CD16 -mDC and memory T reg cells, reflecting the positive impact of these cells in the natural history of T1D (Fig.…”

Section: Discussionmentioning

confidence: 78%

“…Increases either in total counts or percentages of different T cell subsets in T1D have been demonstrated by several authors [22][23][24][25]. The character of changes varies between studies and is due largely to variability in patient populations and methods selection.…”

Section: Discussionmentioning

confidence: 97%

“…Furthermore, it has also been shown that children with higher C-peptide levels at diagnosis have longer periods of remission (i.e. honeymoon phase) [25].…”

Section: Discussionmentioning

confidence: 99%

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

Oras

Peet

Giese

et al. 2019

Clinical and Experimental Immunology

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Type 1 diabetes (T1D) results from autoimmune destruction of insulinproducing beta cells in pancreatic islets. Various immune cell populations are involved in disease development and natural course. However, to our knowledge, so far there are no comprehensive comparative investigations of all main immune cell populations and their most important subsets at the onset of disease. Therefore, in the current study, we analyzed 51 peripheral blood immune cell populations in 22 young T1D patients and in 25 age-matched controls using a comprehensive polychromatic flow cytometry panel developed for whole blood by the COST Action no. BM0907 ENTIRE (European Network for Translational Immunology Research and Education: From Immunomonitoring to Personalized Immunotherapy) consortium. We found that in T1D patients, frequencies and absolute counts of natural killer (NK) cells, dendritic cells (DC) and T cells, aswell as their respective subsets, were significantly altered compared to controls. Further, we observed that changes in several cell populations (e.g. CD14 + CD16 + non-classical monocytes, plasmablasts) were dependent on the age of the patient. In addition to age-related changes, we also found that alterations in immune cell patterns were associated with parameters such as the presence of ketoacidosis and C-peptide serum levels. Our study provides a foundation for future studies investigating different cell lineages and their role in T1D and illustrates the value of polychromatic flow cytometry for evaluating all main peripheral immune cells and their subsets in whole blood samples.

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Section: Discussionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 97%

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

Oras

Peet

Giese

et al. 2019

Clinical and Experimental Immunology

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“…The main research investigating the mechanism can be divided into research investigating immune mechanisms, metabolic mechanisms, and the interactions between these mechanisms. Immune mechanisms The possible mechanisms of immunological tolerance or downregulation during the PR phase have been investigated in some studies by testing the levels of different cytokines and molecules and assessing the changes in immune cells (Table ). Cytokines Significantly lower levels of IFN‐γ and IL‐10 have been reported in T1DM patients, and a higher level of IL‐10 at diagnosis could predict better metabolic control .…”

Section: Immuno‐metabolic Mechanismsmentioning

confidence: 99%

The remission phase in type 1 diabetes: Changing epidemiology, definitions, and emerging immuno‐metabolic mechanisms

Zhong

Tang

Gong

et al. 2019

Diabetes Metabolism Res

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Type 1 diabetes mellitus (T1DM) is characterized by irreversible islet β cell destruction. During the progression of this disease, some patients with T1DM experience a phase of remission known as honeymoon or partial remission (PR) that is mainly characterized by satisfactory glycemic control and the transient recovery of islet β cell function. This special phase is a good model for studying the mechanism of β cell protection, might serve as a proper intervention period for immunotherapy, and may be related to disease prognosis. This special stage is highly valuable for studies aiming to identify possible targets that may be used to cure T1DM. An in-depth understanding of the diagnosis, epidemiology, and possible mechanisms of the PR phase is highly needed. In general, patients enter the PR phase approximately 3 months after starting insulin therapy, and this phase could be sustained for 6 to 9 months. Current research increasingly focuses on the metabolic and immunological aspects to constantly update our understanding of this phase. This review concentrates on the PR phase of T1DM to provide a comprehensive outlook of its epidemiology, diagnostic criteria, and underlying immune metabolic mechanisms. KEYWORDSimmuno-metabolic mechanism, remission phase, the honeymoon period, type 1 diabetes

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“…A sub-group of patients has been shown to maintain an appreciable endogenous ability to produce insulin, as assessed through the monitoring of serum concentration of C-peptide, secreted by β cells at a one-to-one ratio with insulin. Even if typically low, this insulin production is very important since it has been clinically associated with longer periods of remission (i.e., a honeymoon phase) and less severe diabetes-related vascular complications [7,8]. Beside serum concentration of C-peptide, diabetic ketoacidosis (DKA) is most critical in the characterization of T1D.…”

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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Immune cell and cytokine patterns in children with type 1 diabetes mellitus undergoing a remission phase: A longitudinal study

Cited by 21 publications

References 49 publications

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

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

The remission phase in type 1 diabetes: Changing epidemiology, definitions, and emerging immuno‐metabolic mechanisms

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

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