Understanding the Connected Nature of Type 1 Diabetes, Other Autoimmune Diseases

A team of researchers in Indiana has found that the best way to find new treatments for autoimmune diseases, including type 1 diabetes (T1D), is to study the immune system and targeted tissues together, based on an article published earlier this year.

Looking at the immune system in isolation is akin to “attempting to fly a plane with only one wing,” said Decio L. Eizirik, MD, PhD, the scientific director of the Indiana Biosciences Research Institute Diabetes Center, who is the senior author of the paper that appeared in Science Advances.¹

The research, funded in part by the JDRF, springs from the fact that autoimmune diseases are increasing worldwide, and the prevalence of T1D, systemic lupus erythematosus (SLE), multiple sclerosis, and rheumatoid arthritis (RA) has reached 0.5% to 5% depending on the region. JDRF’s clinical research strategy has focused in recent years not only on developing treatments and ultimately cures for T1D, but also on preventing it by screening those at greatest risk of developing the disease, and pursuing interventions to halt its onset.

As the authors wrote, “While the immune targets of T1D, SLE, MS, and RA are distinct, they share several similar elements, including common variants that pattern disease risk, local inflammation with contribution by innate immunity, and downstream mechanisms mediating target tissue damage.”

They focused on the increasing evidence that target tissues “are not innocent bystanders of the autoimmune attack, but participate in a deleterious dialog with the immune system that contributes to their own demise.” In their work, the researchers mined RNA sequencing datasets from relevant organ and tissue cells in the different diseases, and identified “similar and dissimilar gene signatures.” In doing so, they identified both candidate genes for the 4 major diseases as well as major common gene expression changes in tissues among them.

One common gene is TYK2, a protein that regulates interferon signaling. The team showed in its research that use of TYK2 inhibitors - already in use for other autoimmune diseases - protect β-cells against immune-mediated damage.

"This research is significant in reaching the JDRF's mission to cure, treat and prevent T1D," Frank Martin, PhD, JDRF director of research, said in a statement. "Discovering the common pathways of tissue destruction across multiple autoimmune diseases will dramatically accelerate our path to a cure for T1D. Drugs that are effective in one autoimmune disease could be equally beneficial for another and quickly repurposed to make a big impact for people living with that disease. Characterizing the similarities and differences between multiple autoimmune diseases has the potential to transform the way we treat and cure these diseases in the future.”

JDRF has undertaken a large-scale screening project, called T1Detect, that offers participants a blood test to find antibodies, which tell whether a person is at an early stage of T1D and likely to become insulin dependent. The project comes not only as rates of T1D are rising overall, but as they are rising faster among Black and Hispanic youth. The difference now is that there may soon be a treatment at hand.

Another JDRF-funded study, reported last month in Science Translational Medicine, showed that the monoclonal antibody teplizumab delayed the onset of T1D.² FDA has scheduled an advisory panel on teplizumab for May 27 and a targeted action date for the drug is set for July 2, 2021.

References

1. Szymczak F, Colli ML, Mamula MJ, Evans-Molina C, Elzriki DL. Gene expression signatures of target tissues in type 1 diabetes, lupus erythematosus, multiple sclerosis, and rheumatoid arthritis. Sci Adv 10.1126/sciadv.abd7600.
2. Sims EK, Bundy BN, Stier K, et al. Teplizumab improves and stabilizes beta cell function in antibody-positive high-risk individuals. Sci Transl Med. 2021;13:583:eabc8980. DOI: 10.1126/scitranslmed.abc8980