Last year, researchers from Seattle Children’s Research Institute and Benaroya Research Institute at Virginia Mason identified new clues about how a common genetic change in a gene called PTPN22 may predispose children and adults to develop autoimmune conditions, including type 1 diabetes, rheumatoid arthritis and systemic lupus.
Now, this group—in conjunction with researchers from the University of Washington—has taken the research one step further and determined more precisely how PTPN22 alters lymphocyte function, using animal models that very closely model human diabetes. Understanding this process could be crucial for both predicting which individuals are at risk to develop diseases like diabetes and also for designing new therapies.
Lymphocytes, including T cells and B cells, are white blood cells that are responsible for carrying out activities of the immune system. Lymphocytes survey the body and fight against infectious diseases and foreign materials, and need to do so without harming the body itself. Defects in this process play a key role in triggering common and debilitating disorders including type 1 diabetes.
In a new study, “Tony” Xuezhi Dai, PhD, and David Rawlings, MD—both of Seattle Children’s Research Institute—and colleagues found that mice with the identical genetic change in PTPN22 present in humans with autoimmunity progressively develop symptoms of autoimmunity with age. These animals are also more susceptible to induction of diabetes, and this genetic change was found to be critical for controlling B and T cell receptor signaling.
The changes observed in the animal model were very similar to what happens in humans with onset of diabetes or systemic lupus.
The researchers are now focusing on people at risk for diabetes and other autoimmune disorders, drawing on patient samples at, to see if these same kinds of abnormalities take place in patients both with the PTPN22 mutation and in other related signals. They will look for similarly altered pathways that are likely to promote the disease in various patients.
“When we understand these similarities, we can begin to use drugs and inhibitors to target the pathways,” said Dai. “Turning off an abnormal pathway could be used to either reduce the risk for diabetes (or other autoimmune diseases) or allow reversal of these changes in affected individuals.”
Ultimately, the goal is to identify the important genetic pathways and then to use simple tests on a patient’s blood sample to determine who’s at risk for autoimmune conditions. Similar to cancer treatment, physicians would use markers to predict which patients would respond to different types of treatment.