Blood immunoassay for diabetes
In the United States alone, 1.25 million children and adults suffer from type 1 diabetes, and the incidence is increasing for reasons that are not fully understood. In type 1 diabetes, the immune system attacks the beta cells of the pancreas, which are responsible for the production of insulin. Without insulin, the body cannot remove glucose from the bloodstream and deliver it to cells, where it should be used as an energy source. Therefore, people with type 1 diabetes need to closely monitor their blood glucose levels and inject insulin daily.
The diagnosis is often made after the symptoms appear, when the disease has already gained momentum. If there was a way to identify patients from the risk group by the earliest signs of the disease, there might be a chance to delay its manifestation.
In a new study, scientists from the Scripps Institution, California, have discovered the earliest possible biological marker of type 1 diabetes. If the results of their study on mice can be reproduced in humans, then the timing of therapeutic intervention can be radically changed for those patients who are at an early stage of the development of the disease.
Using single-cell technologies to study the pre-diabetic phase of the disease, the researchers were able to link specific anti-insulin T cells to the autoimmune response observed in diabetes. It is known that in patients with type 1 diabetes mellitus, among a certain class of immunoregulatory molecules, the HLA tissue compatibility system is always present.
HLA proteins are located on the surface of cells, informing the immune system whether to attack or not to attack a given cell. This signaling system usually helps to destroy dangerous cells, but it can be life-threatening if the HLA molecule sends the wrong messages. In the case of type 1 diabetes, the mutated HLA protein binds to insulin fragments, causing their destruction by the immune system.
The link between the HLA genetic mutation and type 1 diabetes has been proven, but the scientific community is still unable to determine how T cells are attracted to this mutated molecule. The answer to this question has been sought by Luke Taiton's research group for five years. The work included the evaluation of blood samples from mice with diabetes without obesity at the earliest stage of the disease using advanced methods of structural and computational biology. The team sequenced the DNA of individual T cells for an extremely detailed description of cell function and genetic variation. In total, more than four terabytes of data were obtained in the study.
Among the significant discoveries was a structural mechanism that the authors called the "P9 switch", it allows CD4 T cells to recognize the mutated HLA protein and attack beta cells. It was also found that aggressive anti-insulin T cells are always located in the pancreatic islets next to beta cells. The origin of anti-insulin T cells was not previously known, and some scientists suspected that they were produced in the lymph nodes of the pancreas.
It is noteworthy that P9 caused a pronounced but short-lived anti-insulin response in mice. If this effect is confirmed in humans, immune cells containing the P9 switch may be detected at an early stage of diabetes development. Thus, a blood test that detects these cells can identify people suffering from diabetes mellitus before the first clinical manifestations, providing the possibility of timely treatment.
The Taiton group has received approval for further human studies and plans to take blood samples from 30 people at risk each year, analyzing them for the presence of harbingers of the disease. Type 1 diabetes mellitus has a strong genetic link: having a blood relative with this disease increases the risk by 20 times, so it will be easy to recruit a biomarker monitoring group.
Early diagnosis within five years before clinical progression and the ability to monitor the destruction of beta cells in real time will allow a series of therapeutic interventions aimed at preventing type 1 diabetes mellitus and the development of insulin dependence.
Article by L. Gioia et al. Position β57 of I-Ag7 controls early anti-insulin responses in NOD mice, linking an MHC susceptibility allele to type 1 diabetes onset is published in the journal Science Immunology.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru according to Scripps Research: Discovery paves the way for earlier detection of type 1 diabetes.