JDRF Research
Researchers Clarify Initial Stage of Autoimmune Attack
JDRF-funded researchers in Australia have pinpointed the first trigger that sets off the autoimmune attack destroying beta cells and causing type 1 diabetes in mouse models of type 1 diabetes. The finding reveals that insulin draws the initial attack, which then spreads to other proteins in a more widespread autoimmune assault.
Most people with type 1 diabetes have immune responses to several proteins, or autoantigens, contained within the beta cells. (The immune response is evident by the presence of antibodies that the body develops against the autoantigens.) In people who do not yet have the disease, immune response to several autoantigens increases the likelihood that type 1 diabetes will occur.
It has not been clear how the immune system comes to target several different autoantigens. Researchers did not know if they are all recognized from the beginning—as if the immune system is targeting the entire beta cell—or if one autoantigen draws the initial attack, causing inflammation in the pancreas that makes the other autoantigens targets as well.
The new finding, published in the Journal of Clinical Investigation, clearly shows that insulin is the initial trigger in this model. The autoimmune attack on insulin then spreads to attack other autoantigens. The results were reported by Bala Krishnamurthy in the laboratory of Thomas Kay, Ph.D., at the JDRF Center for Immunoregulation at the Walter and Eliza Hall Institute of Medical Research/University of Melbourne.
The researchers studied insulin and another well-known autoantigen, a protein called IGRP. Working in mice that naturally develop type 1 diabetes, the researchers blocked the immune response to insulin. This prevented the immune response to IGRP, and the mice did not develop the disease. The same method was used to prevent the immune response to IGRP. In this case, the immune response to insulin developed normally and the mice became diabetic, presumably because the attack on insulin spread to other autoantigens.
This indicates that insulin is the “driver” of the autoimmune response. The researchers suggest that people with several beta cell antibodies probably have a more advanced form of type 1 diabetes. And they suggest that preventing the spread in immune recognition—blocking recognition of enough beta cell antigens — might prevent diabetes.