Specialized White Blood Cells Prove Biomarkers for Diabetes Progression

Researchers have found that a specialized class of circulating white blood cells (CXCR5−PD-1hi Tph cells) are associated with progression for autoantibody positivity to clinical type I diabetes and have the potential to serve as biomarkers to monitor progression of this disease.

Type I diabetes is preceded by a period of asymptomatic autoimmunity characterized by positivity for pancreatic islet autoantibodies. Therefore, T helper cell responses that induce B-cell activation are likely to play a critical role in the disease process.

To better understand the role of B-cell activation in type I diabetes, investigators at the University of Eastern Finland (Kuopio, Finland) aimed to evaluate the role of a recently described subset, C-X-C motif chemokine receptor type 5-negative, programmed cell death protein 1-positive (CXCR5−PD-1hi) peripheral T helper (Tph) cells, in human type I diabetes. C-X-C chemokine receptor type 5 (CXC-R5) is a G protein-coupled seven transmembrane receptor for chemokine CXCL13 (also known as BLC) and belongs to the CXC chemokine receptor family. It enables T-cells to migrate to lymph node B- cell zones.

Previous studies had found that the appearance of autoantibodies before clinical diabetes was caused by follicular helper T-cell activation of B-cells against proteins in the pancreatic islets. Peripheral helper T-cells (Tph) resemble follicular helper T-cells, but they express receptors that enable them to migrate to inflamed tissues.

For the current study, the investigators utilized samples from the Finnish DIPP (Type I Diabetes Prediction and Prevention) study in which the development of type I diabetes was followed from birth in children with genetic risk for the disease.

The frequencies of circulating CXCR5−PD-1hi T cells were analyzed by multicolor flow cytometry in a cohort of 44 children with newly diagnosed type I diabetes, 40 autoantibody-positive (AAb+) at-risk children, and 84 autoantibody-negative healthy control children. The findings were subsequently replicated in a separate cohort of 15 children with newly diagnosed type I diabetes and 15 healthy control children.

Results revealed that the frequency of circulating Tph cells was increased in children with newly diagnosed type I diabetes, especially in those who were positive for multiple autoantibodies. Importantly, circulating Tph cells were also increased in autoantibody-positive at-risk children who later progressed to type I diabetes.

"Based on our results, it is possible that peripheral helper T-cells may have a role in the development of type I diabetes. This information could be employed in the development of better methods to predict type I diabetes risk and new immunotherapies for the disease. However, more studies need to be conducted to verify our results and to further characterize the functionality of peripheral helper T- cells," said first author Ilse Ekman, a doctoral research student at the University of Eastern Finland.

The study was published in the September 2019 issue of the journal Diabetologia.

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