Circulating B cells in type 1 diabetics exhibit fewer maturation-associated phenotypes

Hanley, Patrick C; Sutter, Jennifer A.; Goodman, Noah; Du, Yunpeng; Sekiguchi, Debora R.; Meng, Wenzhao; Rickels, Michael R.; Naji, Ali; Prak, Eline Luning

doi:10.1016/j.clim.2017.09.021

Cited by 28 publications

(33 citation statements)

References 76 publications

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“…It is also notable that we did not detect increased expression levels of CD95 on switched memory B cells, as described previously in individuals with rheumatoid arthritis [26]. Instead, we found that CD95 expression was reduced on switched CD27 + IgD − memory B cells in individuals with long-standing diabetes, consistent with the findings of a recent study by Hanley and colleagues, who also reported lower frequencies of CD24 ++ CD38 ++ B cells in people with type 1 diabetes [27]. This latter phenotype is indicative of regulatory B cells [28], but does not match the profiles we identified in areas 2 and 6 of the SPADE tree, where reduced expression of CD24 was apparent in newly diagnosed individuals and those with long-standing diabetes.…”

Section: Discussionsupporting

confidence: 91%

Loss of CXCR3 expression on memory B cells in individuals with long-standing type 1 diabetes

et al. 2018

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Aims/hypothesisIslet-specific autoantibodies can predict the development of type 1 diabetes. However, it remains unclear if B cells, per se, contribute to the causal pancreatic immunopathology. We aimed to identify phenotypic signatures of disease progression among naive and memory B cell subsets in the peripheral blood of individuals with type 1 diabetes.MethodsA total of 69 participants were recruited across two separate cohorts, one for discovery purposes and the other for validation purposes. Each cohort comprised two groups of individuals with type 1 diabetes (one with newly diagnosed type 1 diabetes and the other with long-standing type 1 diabetes) and one group of age- and sex-matched healthy donors. The phenotypic characteristics of circulating naive and memory B cells were investigated using polychromatic flow cytometry, and serum concentrations of various chemokines and cytokines were measured using immunoassays.ResultsA disease-linked phenotype was detected in individuals with long-standing type 1 diabetes, characterised by reduced C-X-C motif chemokine receptor 3 (CXCR3) expression on switched (CD27+IgD−) and unswitched (CD27intermediateIgD+) memory B cells. These changes were associated with raised serum concentrations of B cell activating factor and of the CXCR3 ligands, chemokine (C-X-C motif) ligand (CXCL)10 and CXCL11. A concomitant reduction in CXCR3 expression was also identified on T cells.Conclusions/interpretationOur data reveal a statistically robust set of abnormalities that indicate an association between type 1 diabetes and long-term dysregulation of a chemokine ligand/receptor system that controls B cell migration.Electronic supplementary materialThe online version of this article (10.1007/s00125-018-4651-x) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

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Section: Discussionsupporting

confidence: 91%

Loss of CXCR3 expression on memory B cells in individuals with long-standing type 1 diabetes

et al. 2018

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“…In contrast to some previous studies [6,29], in our study the B cell compartment in T1D patients did not differ from controls. However, in one study focusing on patients with long-standing T1D, T1D patients did not differ from controls in most B cell subpopulations, but the expression of maturation-associated markers was impaired in T1D patients [30]. This may indicate that the B cell compartment is largely involved in the T1D pathogenesis through functional defects.…”

Section: Discussionmentioning

confidence: 96%

“…B cells also have regulatory and effector functions mediated by cytokines and chemokines [28]. However, in one study focusing on patients with long-standing T1D, T1D patients did not differ from controls in most B cell subpopulations, but the expression of maturation-associated markers was impaired in T1D patients [30]. However, in one study focusing on patients with long-standing T1D, T1D patients did not differ from controls in most B cell subpopulations, but the expression of maturation-associated markers was impaired in T1D patients [30].…”

Section: Discussionmentioning

confidence: 99%

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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“…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: 96%

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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Circulating B cells in type 1 diabetics exhibit fewer maturation-associated phenotypes

Cited by 28 publications

References 76 publications

Loss of CXCR3 expression on memory B cells in individuals with long-standing type 1 diabetes

Loss of CXCR3 expression on memory B cells in individuals with long-standing type 1 diabetes

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

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

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