What is already known
Teplizumab is the first FDA-approved treatment to delay the onset of type 1 diabetes, an autoimmune disease that originates when pancreas’ beta cells, which make insulin, are destroyed by the immune system. Teplizumab is an antibody that targets immune cells and prevents them from destroying beta cells. However, not all patients benefit from the treatment.
What this research adds
Researchers analyzed the antibodies present in blood samples from 63 participants in a teplizumab trial both before and after treatment. People who had longer-lived antibody responses to three species of gut bacteria — Bifidobacterium longum, Enterococcus faecalis, and Dialister invisus — went a longer time on teplizumab treatment before they were diagnosed with type 1 diabetes. People with high antibody responses to B. longum and D. invisus also had longer times to diagnosis in an independent group of 61 pre-diabetic patients.
Conclusions
The findings indicate that antibodies to gut microbes could help identify who may benefit from teplizumab.
Teplizumab is the first approved treatment to delay the onset of type 1 diabetes, an autoimmune disease that originates when pancreas’ beta cells, which make insulin, are destroyed by the immune system. But not all patients respond to the treatment. Now, researchers have found that patients with stronger immune responses against specific gut bacteria tended to benefit more from the drug’s disease-delaying effects.
The findings, published in Science Translational Medicine, indicate that antibodies to gut microbes could help identify who may benefit from teplizumab.
Teplizumab is an antibody that targets immune cells called T cells and prevents them from destroying beta cells. The US drug regulator has recently approved the treatment for delaying type 1 diabetes onset based on the results of a clinical trial called TrialNet 10 (TN-10). “The TN-10 trial provided the first demonstration that a T cell-directed therapy could delay onset of an autoimmune disease,” the researchers say. However, they add, “participant responses were heterogeneous.”
The same team previously reported that antibody responses to gut microbes were associated with a diagnosis of type 1 diabetes, suggesting that certain immune responses to gut bacteria may help predict disease onset. So, the researchers — led by Quin Yuhui Xie at the University of Toronto in Canada — analyzed the antibodies present in blood samples from 63 participants in the TN-10 trial.
Diabetes risk
The researchers measured the abundance of antibodies against a panel of 31 commensal gut bacteria representing 15 common species.
People who had longer-lived antibody responses to three species of gut bacteria — Bifidobacterium longum, Enterococcus faecalis, and Dialister invisus — went a longer time on teplizumab treatment before they were diagnosed with type 1 diabetes.
Teplizumab’s effect was more evident in participants who had high baseline immune responses to B. longum or E. faecalis. “These data support previous suggestions that [type 1 diabetes] is associated with gut microbial responses that produce a non-inflammatory, homeostatic state,” the researchers say.
Untangling heterogeneity
Next, the team sought to validate the associations between antimicrobial antibody responses and time to diabetes diagnosis in an independent group of 61 pre-diabetic patients.
People with high antibody responses to B. longum and D. invisus had longer times to diagnosis, the researchers found. B. longum is abundant in the infant gut microbiota, but it can persist in the adult gut microbiota. Previous work has shown that insufficient early immune exposure to this bacteria species is associated with increased risk of developing type 1 diabetes.
“[Anti-commensal antibody] responses have potential to guide the recruitment of individuals for [type 1 diabetes] trials and offer approaches to identify markers to untangle the heterogeneity in responses to immunotherapies,” the authors say.
