DNA methylation markers as early biomarkers of immunological changes in the development of type 1 diabetes

In order to expand our understanding of this topic, the researchers decided to analyse the proportions immune cells – determined on the basis of DNA methylation patterns – by comparing patients with type 1 diabetes and a matched control group during the critical period of seroconversion.

To this end, a method was used to assess cell types based on DNA methylation (DNAm) in peripheral blood. The analysis included samples from from participants in two large, prospective paediatric studies: DAISY (151 individuals) and TEDDY (166 individuals). The percentages of individual cell types were estimated at two time points: during the last visit prior to seroconversion and at the time of the event itself (defined as the first visit with persistently detectable autoantibodies).

The study revealed a link between diabetes and changes in non-coding genes. Until recently, most research into the genetic basis of diabetes had focused on coding genes – those that produce proteins. However, a recent analysis published in the *American Journal of Human Genetics* suggests, however, that diabetes occurring in infants may be caused by non-coding genes.

The results showed that in children from the control group, there was a physiological, puberty-related increase in the NLR ratio and the proportion of memory cells to naive cells. In patients who developed the disease, however, these processes were markedly disrupted, and the physiological increase in these ratios was significantly inhibited (by 21 per cent, 35 per cent and 38 per cent, respectively).

Furthermore, even before seroconversion occurred, in future patients a 15 per cent higher NLR and a 9 per cent lower CD4+ to CD8+ lymphocyte ratio were observed. In turn, at the very moment of antibodies appeared, the overall ratio of memory cells to naive cells was reduced by 26 per cent in these patients. The abnormalities described may reflect enhanced activation of neutrophils, an imbalance in T-cell subpopulations, and delayed maturation of the immune system following exposure to antigens.

The results demonstrate the existence of early disturbances in cellular dynamics in patients during the development of type 1 diabetes.

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