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

Acta Diabetol. 2020 Mar;57(3):297-307. doi: 10.1007/s00592-019-01427-1. Epub 2019 Sep 30.

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.

Keywords: C-peptide; Immune system; Partial remission; Type 1 diabetes.

MeSH terms

  • Adaptive Immunity*
  • Adolescent
  • Age of Onset
  • B-Lymphocytes / immunology
  • C-Peptide / blood
  • Child
  • Child, Preschool
  • Cohort Studies
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / immunology*
  • Female
  • Glycated Hemoglobin / metabolism
  • Humans
  • Immunity, Innate*
  • Insulin / blood
  • Insulin-Secreting Cells / metabolism
  • Leukocyte Count
  • Male
  • Prospective Studies
  • T-Lymphocytes, Regulatory / immunology

Substances

  • C-Peptide
  • Glycated Hemoglobin A
  • Insulin
  • hemoglobin A1c protein, human