Scripps Research scientists have shown that analyzing a certain sort of immune cell within the blood will help discover people vulnerable to developing type 1 diabetes, a life-threatening autoimmune disease. The brand new approach, if validated in further studies, may very well be used to pick out suitable patients for treatment that stops the autoimmune process-; making type 1 diabetes a preventable condition.

Within the study, which appeared in Science Translational Medicine on July 5, 2023, the researchers isolated T cells (a sort of immune cell) from mouse and human blood samples. By analyzing the T cells that may cause type 1 diabetes, they were able to tell apart the at-risk patients who had lively autoimmunity from those that had no significant autoimmunity-; with 100% accuracy in a small sample.

These findings represent an enormous step forward because they provide the potential for catching this autoimmune process while there continues to be time to stop or greatly delay diabetes.”

Luc Teyton, MD, PhD, study senior writer, professor, Department of Immunology and Microbiology at Scripps Research

The study’s first authors were graduate student Siddhartha Sharma and research assistants Josh Boyer and Xuqian Tan, all the Teyton lab on the time of the study.

Type 1 diabetes occurs when the immune system destroys the insulin-producing “islet cells” of the pancreas. The autoimmune process that underlies type 1 diabetes can occur over years, with multiple starts and stops. Exactly how the method begins will not be well understood, though it is thought to involve genetic aspects and should be triggered by routine viral infections. When it occurs, it often does so in childhood or early maturity, and requires lifelong insulin alternative. Researchers estimate that about two million people have type 1 diabetes within the U.S. alone.

In 2022, the U.S. Food & Drug Administration approved an immune-suppressing therapy that may protect islet cells and no less than delay diabetes onset by months to years if given within the early stages of autoimmunity. Nevertheless, doctors haven’t had a great method for identifying individuals who may gain advantage from such treatment. They’ve traditionally examined levels of anti-islet antibodies in patient blood samples, but this antibody response has not been a really accurate measure of autoimmune progression.

“Anti-islet antibody levels are poorly predictive at the person level, and kind 1 diabetes is fundamentally a T cell-driven disease,” Teyton says.

Within the study, Teyton and his team constructed protein complexes to mimic the combo of immune proteins and insulin fragments that specialized T cells called CD4 T cells normally would recognize to initiate the autoimmune response. They used these constructs as bait to capture anti-insulin CD4 T cells in blood samples. They then analyzed the gene activity inside the captured T cells, and expression of proteins on the cells, to gauge their state of activation.

In this manner, they were capable of develop a classification algorithm that accurately identified which at-risk patients, in a set of nine, had ongoing anti-islet autoimmunity.

Teyton now hopes to validate the CD4 T cell-based approach with a long-term study in a bigger cohort of participants, comparing this approach to the normal approach of quantifying anti-islet antibodies.

Teyton and his colleagues are also working to make the strategy of isolating and analyzing anti-islet T cells in blood samples cheaper and convenient, in order that it could possibly be used more easily in a clinical setting.

“If we will develop this right into a useful method for identifying at-risk patients and tracking their autoimmunity status, we not only would have a way of getting the best people into treatment, but additionally would have the ability to watch their disease progress and evaluate potential latest preventive therapies,” Teyton says.

Source:

Scripps Research Institute

Journal reference:

Sharma, S., et al. (2023) Measuring anti-islet autoimmunity in mouse and human by profiling peripheral blood antigen-specific CD4 T cells. Science Translational Medicine. doi.org/10.1126/scitranslmed.ade3614.