Test detects earliest stages of autoimmune assault that causes type 1 diabetes

 An investigational blood test for type 1 diabetes can accurately detect the disorder's characteristic autoimmunity with only small samples of blood, a feature that makes it ideal to screen pediatric patients, scientists in Australia report in a new study.

The assay provides a useful tool to confirm and track autoimmunity, the assault by turncoat forces of the immune system that destroy insulin-producing beta cells in the pancreatic islets of Langerhans. The attack is the central deleterious event in type 1 diabetes.

In an article published in Science Translational Medicine, a multidisciplinary team of medical investigators from throughout Australia describe a first-of-its-kind test that they developed and named BASTA, which stands for "β cell antigen-specific T cell assay."

The test serves as an alert to what ultimately becomes one of the most destructive and potentially lethal acts of collusion in human biology—the activity of two types of T cells against the pancreas. The pair of T cells conspire in a relentless assault against pancreatic β cells, forcing patient victims into lifelong exogenous insulin dependence.

Researchers theorize that the test could eventually allow them to better understand how the immune response changes as type 1 diabetes progresses and how it may be dampened with new therapies in the future.

"Type 1 diabetes is a T cell-mediated autoimmune disease arising from the destruction of pancreatic insulin-producing β cells found within the islets of Langerhans in the pancreas," write Drs. Matthew Lacorcia, lead author of the research, and Stuart I. Mannering, the study's principal investigator.

"β cell antigen–specific CD4+ and CD8+ T cells collaborate to mediate β cell destruction," the two scientists report. Both investigators conduct research in the Immunology and Diabetes Unit at St. Vincent's Institute of Medical Research in Melbourne, Australia.

The test that they developed allows detection at the earliest signs of the immune system assault against the pancreas, which is an advantage because most patients being tested for type 1 diabetes are children and teens. Testing in the earliest possible stage of the disorder allows intervention to begin sooner.

Prior to the development of BASTA, the only way to test for autoimmune destruction of pancreatic islet cells was to analyze autoantibodies—anti-self-proteins that target and react with an individual's own tissues. More complicated still is measuring T cell activity against β cell antigens. Before BASTA, that could be done only in research settings because of the complexity of assays and the large blood volumes required.

"BASTA is a simple whole-blood assay that can detect human CD4+ T cell responses to β cell antigens by measuring antigen-stimulated interleukin-2 production," the researchers wrote, noting that interleukin-2 functions as a proxy for anti-beta cell autoimmunity.

The researchers demonstrated that they could perform the test with only 2 to 3 milliliters of whole blood, making it suitable for pediatric patients. BASTA, they add, is both more sensitive and specific than the standard research lab test known as a carboxyfluorescein diacetate succinimidyl ester–based proliferation assay.

Lacorcia and Mannering worked with a team of collaborators at their own institution as well as with investigators from elsewhere in Australia. They say BASTA could prove to be especially useful for children due to its simplicity and modest blood requirements. The test is capable of capturing immune responses to peptides in pre-proinsulin, a precursor to insulin.

"We used BASTA to identify the regions of pre-proinsulin that stimulated T cell responses specifically in blood from people with type 1 diabetes," Lacorcia and Mannering wrote. They noted that they also found that effector memory CD4+ T cells are the primary producers of interleukin-2 in response to pre-proinsulin peptides.

"We then evaluated responses to individual and pooled pre-proinsulin peptides in a cross-sectional study of pediatric patients: without type 1 diabetes, without type 1 diabetes but with a first-degree relative with type 1 diabetes, or diagnosed with type 1 diabetes," the researchers explained.

In all, they analyzed the efficiency of their test in 64 children and adolescents. This included 10 low-risk participants, 22 participants with a relative with type 1 diabetes, and 32 participants diagnosed with the disease. BASTA showed a high specificity for type 1 diabetes, data in the study revealed.

"Because of its simplicity and robustness, we believe BASTA will be a useful and powerful tool for both dissecting autoimmune CD4+ T cell responses and monitoring changes in clinical trials and community settings," Lacorcia and Mannering concluded.

More information: Matthew Lacorcia et al, BASTA, a simple whole-blood assay for measuring β cell antigen–specific CD4+ T cell responses in type 1 diabetes, Science Translational Medicine (2025). DOI: 10.1126/scitranslmed.adt2124. www.science.org/doi/10.1126/scitranslmed.adt2124

https://medicalxpress.com/news/2025-04-earliest-stages-autoimmune-assault-diabetes.html