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Changes in innate and adaptive immunity over the first year after the onset of type 1 diabetes

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Abstract

Aims

The development of the immune phenotype in patients with type 1 diabetes (T1D) during the first year following disease onset remains poorly described, and studies analysing the longitudinal development of a complex set of immunological and metabolic parameters are missing. Thus, we aim to provide such complex view in a cohort of 38 children with new onset T1D who were prospectively followed for 1 year.

Methods

All subjects were tested for a set of immunological parameters (complete blood count; serum immunoglobulins; and T, B and dendritic cells), HbA1c and daily insulin dose at baseline and at 6 and 12 months after T1D diagnosis. A mixed meal tolerance test was administered to each of the subjects 12 months after diagnosis, and the C-peptide area under the curve (AUC) was noted and was then tested for association with all immunological parameters.

Results

A gradual decrease in leukocytes (adjusted p = 0.0012) was reflected in a significant decrease in neutrophils (adjusted p = 0.0061) over the post-onset period, whereas Tregs (adjusted p = 0.0205) and originally low pDCs (adjusted p < 0.0001) increased. The expression of the receptor for BAFF (BAFFR) on B lymphocytes (adjusted p = 0.0127) markedly increased after onset. No immunological parameters were associated with C-peptide AUC; however, we observed a linear increase in C-peptide AUC with the age of the patients (p < 0.0001).

Conclusions

Our study documents substantial changes in the innate and adaptive immune system over the first year after disease diagnosis but shows no association between immunological parameters and residual beta-cell activity. The age of patients remains the best predictor of C-peptide AUC, whereas the role of the immune system remains unresolved.

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Abbreviations

ADA:

American Diabetes Association

ANOVA:

Analysis of variance

AUC:

Area under curve

BAFFR:

B-cell activating factor receptor

BE:

Base excess

BMI:

Body mass index

CD:

Cluster of differentiation

ELISA:

Enzyme-linked immunosorbent assay

GAD65:

Glutamate decarboxylase isoform 65

HbA1c:

Haemoglobin A1C

IA2:

Islet antigen 2

IAA:

Insulin autoantibodies

IFCC:

International Federation of Clinical Chemistry

IFNγ:

Interferon γ

IDAA1c:

Insulin dose-adjusted HbA1c

mDC:

Myeloid dendritic cell

MFI:

Mean fluorescence intensity

MMTT:

Mixed meal tolerance test

PBMC:

Peripheral blood mononuclear cell

pDC:

Plasmacytoid dendritic cell

PMA:

Phorbol myristate acetate

SD:

Standard deviation

T1D:

Type 1 diabetes

TDD:

Total daily insulin dose

Treg:

T regulatory lymphocyte

Th17:

T-helper 17 lymphocytes

Th1:

T-helper 1 lymphocytes

ZnT8:

Zinc transporter 8

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Funding

This study was funded in part by a grant from the Czech Ministry of Health AZV 16-32838A and by the Institutional Support of Research Organization 00064203 (University Hospital Motol).

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Author notes

  1. A. Klocperk and L. Petruzelkova have contributed equally to this work.

Authors and Affiliations

  1. Department of Immunology, 2nd Faculty of Medicine, Charles University and University Hospital in Motol, Prague, Czech Republic

    Adam Klocperk, Michal Rataj, Jana Kayserova, Zuzana Parackova & Anna Sediva

  2. Department of Pediatrics, 2nd Faculty of Medicine, Charles University and University Hospital in Motol, Prague, Czech Republic

    Lenka Petruzelkova, Stepanka Pruhova, Stanislava Kolouskova, Jana Sklenarova & Zdenek Sumnik

  3. Department of Probability and Mathematical Statistics, Faculty of Mathematics and Physics, Charles University, Prague, Czech Republic

    Marketa Pavlikova

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  1. Adam Klocperk
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Contributions

AK and LP designed the study; produced, analysed and interpreted the data; and wrote the manuscript. MP performed the bioinformatical analysis. MR and JS performed the experiments and produced the data. JK designed the study. SP, SK and ZS provided patient material and co-wrote the manuscript. AS designed the study, interpreted the data and co-wrote the manuscript.

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Correspondence to Adam Klocperk.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee (Ethics Committees of the University Hospital Motol and 2nd Faculty of Medicine, Charles University in Prague, Czech Republic) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Klocperk, A., Petruzelkova, L., Pavlikova, M. et al. Changes in innate and adaptive immunity over the first year after the onset of type 1 diabetes. Acta Diabetol 57, 297–307 (2020). https://doi.org/10.1007/s00592-019-01427-1

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