Partial remission and early stages of pediatric type 1 diabetes display immunoregulatory changes. A pilot study

Abstract

Type 1 diabetes (T1D) is a chronic metabolic disease of unknown etiology that results from b-cell destruction. The onset of the disease, which arises after a long asymptomatic period of autoimmune attack, may be followed by a relapsing and remitting progression, a phenomenon that is most evident during the partial remission phase (PR). This stage lasts for a few months, shows minor requirements of exogenous insulin and could be explained by a recovery of immunological tolerance. This study aims to identify new biomarkers at early stages of pediatric T1D that reflect immunoregulatory changes. To that end, pediatric patients with T1D (n = 52) and age-related control subjects (n = 30) were recruited. Immune response-related molecules and lymphocyte subsets were determined starting at T1D onset and until the second year of progression. Results showed that circulating TGF-b levels decreased during PR, and that betatrophin concentration was increased in all the considered stages without differing among studied checkpoints. Moreover, an increase of regulatory T, B and NK subsets was found during T1D progression, probably reflecting an attempt to restore self-tolerance. By contrast, a reduction in monocyte levels was observed at the early stages of diabetes. The results reveal significant changes in immunological parameters during the different early stages of T1D in children, which could ultimately serve as potential biomarkers to characterize the progression of T1D.

Antigen-specific immunotherapy combined with a regenerative drug in the treatment of experimental type 1 diabetes

“…All mice with more than 10% of human/murine CD45 chimerism at day 13 were injected either with PBS (n = 3) or the combined therapy (n = 7). Then, a blood sample (50 µl) was obtained at each checkpoint and stained as previously described 23 . The percentage and count of memory regulatory T cells (mTregs, CD3 + CD4 + CD127 low CD25 + CCR4 + CD45RO + ) were analysed weekly throughout the treatment, and total T lymphocyte subsets were analysed at endpoint by flow cytometry from peripheral blood samples.…”

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

“…A study in 2018 also found that the remission phase was accompanied by dynamic changes in Treg cells, Th1 and Tc1-cell subsets (13), with the decreased number of Treg cells and increased Th1 and Tc1 cells at the end of the remission phase. 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).…”

“…A study showed that the frequency changes of marginal zone B cells (MZB), follicular B cells (FoB), and other B-cell subsets were associated with T1DM, and the regulatory B cells (Breg) have immunomodulatory effects (30). Limited reports showed that the remission phase was accompanied by changes in B-cell frequency (13, 15). Glucose metabolism had also been shown to play an important role in the normal functioning of B cells.…”

“…In 2018, Fitas et al (13) found that the absolute number and relative frequency of B cells decreased significantly during the disease course when compared with the onset stage and hit the lowest level in the remission phase. A recent study found that the Breg cells significantly increased during the remission phase (15). In addition, the study showed that the intervention of the anti-CD20 monoclonal antibody rituximab can extend the duration of the remission phase to 2 years (31).…”

“…An animal studied showed that Breg subpopulations that secrete IL-10 (CD1d hi CD5 + , B10) can effectively inhibit the proliferation of effector T cells and alleviate the decline in β-cell function by secret IL-10 (32). Breg cells were increased in the early recovery stage of T1DM (15), and the B10 subgroup was positively correlated with fasting C-peptide level and negatively correlated with HbA1c of T1DM patients (30). The evidence suggests that B-cell subsets participate in the process of the remission phase.…”