Researchers at Scripps Research Institute have identified a biomarker for type 1 diabetes using single cell analysis techniques that could be used to diagnose patients during the pre-diabetic stage of the disease.
Type 1 diabetes is an autoimmune disorder in which the body loses the ability to produce insulin, the hormone responsible for controlling blood sugar levels in the blood. The immune systems of patients suffering from type 1 diabetes attack the cells in the pancreas responsible for producing insulin – beta cells. No other cells produce insulin, so without those cells it is not possible for patients to control their blood sugar levels. Around 1.25 million Americans suffer from type 1 diabetes and that number is increasing. Those individuals must monitor their blood sugar levels daily and inject insulin. Without insulin injections, the disease is fatal.
Type 1 diabetes typically emerges before the age of 20 and it is usually diagnosed when the first symptoms of the disease are experienced. By the time the symptoms manifest, the patient is already in the full throws of the disease.
If the disease can be identified in the pre-diabetic phase, therapeutic intervention could delay the onset of the disease. However, in order to test for the disease, a biomarker must be identified. The Scripps researchers believe they have found just such a biomarker in mice.
Over five years, the researchers studied blood samples in non-obese diabetic mice and used advanced structural and computational techniques to study how the immune system attacks beta cells and triggers the disease. The techniques used in the study have never before been used to study these cell types.
The researchers identified a structural mechanism – termed the P9 switch – which allows C4+ T-cells to recognize a mutated HLA protein on the surface of beta cells. The T-cells then attack the beta cells. In addition to identifying this P9 switch, the researchers also identified the location of these beta cell-killing T cells. Until this study, it was unclear where the anti-insulin T-cells originated.
“By using single-cell technologies to study the prediabetic phase of disease, we have been able to mechanistically link specific anti-insulin T cells with the autoimmune response seen in type 1 diabetes. And that has given us the confirmation we needed to move into human studies,” said Luc Teyton, professor of immunology and microbiology at the institute, and lead researcher for the study.
The researchers are now moving onto trials on humans to see if they can replicate the results of their mouse study. They will be recruiting 30 at-risk individuals a year and will test for the presence of the anti-insulin T-cells. If the results of the mouse study are replicated, a blood test for the T-cells could be developed and therapeutic interventions could allow doctors to slow the progression of the disease and improve the quality of life of patients.
The research is detailed in the paper – Position β57 of I-Ag7 controls early anti-insulin responses in NOD mice, linking an MHC susceptibility allele to type 1 diabetes onset- which was recently published in the journal Science Immunology. DOI: 10.1126/sciimmunol.aaw6329