Study looks into how genetics affect immunity in type 1 diabetic patients

recently discovered new insights on how hereditary variables impact the body’s immunological response in type 1 diabetes.

The findings, published in eLife, show a clear relationship between genetic variables linked with type 1 diabetes susceptibility and immunological functioning, specifically immune T cells. They also indicate 11 genes that might be investigated as possible therapy possibilities. Type 1 diabetes occurs when the immune system incorrectly assaults groupings (or islets) of insulin-producing beta cells in the pancreas. There are currently over nine million individuals living with type 1 diabetes. There is no cure and patients must get insulin injections on a regular basis to control the illness. Type 1 diabetes is more common in those who have particular genetic abnormalities.

However, while earlier research has found over 60 related variants, it is still unknown how they impact the illness.

Xiaojing Chu, a doctoral student at the University Medical Center Groningen in the Netherlands, explains that to characterise the body’s immune response in type 1 diabetes, we need to look at both the proportion of immune cells and their production of proteins that stimulate the immune system, called cytokines, Chu is a co-first author of the study at Radboud University Medical Center in the Netherlands, together with Anna Janssen, a medical doctor and PhD Candidate, and Hans Koenen, an Assistant Professor.

“In this study, we investigated how genetic variables impact immune cells and cytokine production in people with type 1 diabetes, as well as the disparities between the immune response in patients and a healthy response,” Xiaojing noted.

To do this, the researchers obtained blood samples from 243 individuals of Dutch heritage aged 20 to 84 years old who had type 1 diabetes. They then used a technique known as genetic association analysis to discover genetic drivers of immunological functioning in over 200 immune cell features and over 100 cytokine production profiles. They compared the results to those obtained in prior studies of 500 healthy adults that described the influence of genetic variables on immunological responses in these individuals.

Their findings reveal that the genetic variations that determine susceptibility to type 1 diabetes have a considerable impact on T-cell composition. A subset of these cells, known as CCR5+ regulatory T cells, was found to be actively implicated in type 1 diabetes via a region of the genome known as the restricted coding region.

The researchers next examined immunological features using a technique known as genome-wide quantitative trait loci (QTL) mapping. This discovered 15 genetic ‘commands’ that regulate immune cell behaviour in type 1 diabetes. Twelve of these have never been documented in healthy people, indicating disease-specific genetic control. In addition, the scientists identified 11 genes as possible drug development prospects.

“Our findings contribute to a better understanding of the immunological processes that contribute to the development of type 1 diabetes and influence the overall inflammatory response in patients. We expect that our research will pave the way for the development of much-needed medicines “Yang Li, Professor of Computational Biology and Director of the Helmholtz Centre for Infection Research’s Centre for Individualised Infection Medicine (CiiM), Hannover, Germany, concludes. Li co-authored the paper with Cees Tack, Professor of Internal Medicine at Radboud University Medical Center in Nijmegen, the Netherlands.