A previously unknown pathological process in type 1 diabetes (T1D) may hold the key to immune therapy that corrects defective immune function.

A series of experiments in a study published in the Diabetes journal in November 2018 have reversed new-onset diabetes in non-obese diabetic (NOD) mice, a potentially exciting discovery that could have far-reaching impact in preventing or reversing T1D. There are no current high-performing approaches to retrain immunity to prevent T1D.

Honing in on Immunoglobulin M

The experiments—conducted by investigators at Vanderbilt University Medical Center — centered around the effects of purified immunoglobin M (IgM) antibodies, which previous research has suggested can protect against the development of T1D.

“We were pretty skeptical at first that such a simple and benign molecule could have significant effects on immune function,” said Daniel Moore, M.D., assistant professor of pediatrics at Vanderbilt. “We were excited to find that just one or two small doses completely reversed diabetes in mice with autoimmune T1D.”

“One or two small doses completely reversed diabetes in mice with autoimmune T1D.”

The Vanderbilt study suggests that natural IgM is important for regulation of B lymphocytes and the development of regulatory T cells (Treg), which prevent auto-immunity. In their attempt to reverse T1D, researchers injected donor IgM from healthy mice and humans into diabetes-prone NOD mice. The result was profoundly improved blood sugars and immune function for the diabetic mice. The study’s authors propose that IgM might be an alternative to current immunosuppressant approaches and might translate as a clinical approach to preventing or reversing type 1 diabetes.

A connection to immune function

“Surprising to us, we found that treatment with IgM actually enhanced healthy immunity rather than suppressing it, which is what all other immune therapies for T1D have tried,” Moore said. “We believe that restoring normal immune function may be the best approach to an effective and durable treatment for T1D.”

The purified IgM collected from healthy mice and used for treatment in the NOD mice eliminated autoreactive B lymphocytes and enhanced regulatory T cell numbers, along with reversing T1D. The human IgM was used in humanized mice, expanded human Treg numbers, and resulted in permanent diabetes protection. Another finding of note from the Vanderbilt experiments was that IgM derived from pre-diabetic NOD donors did not reverse diabetes and did not expand Treg numbers, suggesting that loss of this function is a potential clue into how T1D develops.

Next Steps

The promising results of IgM in NOD mice deliver hope that researchers are one step closer to reversing, says Moore.

“I am very excited by our new insight that this protective factor could be something that people with T1D either don’t have or lose as they progress to disease. My team is eager to obtain support for studies in persons at risk for type 1 diabetes so we can determine what happens to the protection provided by IgM over time, and so we can find the right time and way to apply it as a treatment.”

About the Expert

Daniel Moore, M.D.

Daniel Moore, M.D., Ph.D., is an assistant professor of pathology, microbiology and immunology, and pediatrics at Vanderbilt University Medical Center. He is a pediatric endocrinology and diabetes specialist, with a research focus on type 1 diabetes and organ transplantation.