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May 7, 2025

Autoantibody Reversion: A Mystery That Could Help Prevent T1D

Scientists can predict who will develop type 1 diabetes (T1D) with almost 100% accuracy. They use a blood test to look for five specific proteins called autoantibodies. People who have two or more of those autoantibodies have a nearly 100% chance of developing T1D.

For years, BRI’s Cate Speake, PhD, has wondered: What about the tiny percentage of people who don’t develop T1D? 

Thanks to decades of data from TrialNet and hundreds of thousands of research participants, Dr. Speake was able to analyze data for enough people within the group who don’t appear to get T1D to look for meaningful patterns.

Graphic Layout Autoantibody Reversion 1

She found something no one expected.

Now, she’s working to find out exactly what’s happening in these people’s immune systems, thanks to a new grant from The Leona M. and Harry B. Helmsley Charitable Trust.

“This research could teach us something really important about how to treat or prevent T1D,” Dr. Speake says.

Cate Speake

An Unexpected Finding

Dr. Speake and other scientists have anecdotally observed something strange over the past decade: A handful of people where one blood test showed they had two autoantibodies but then subsequent blood tests showed only one autoantibody.

At first, many scientists thought this might be an error — an imperfection with the blood test or a problem with data collection. But the more data they collected, the more they saw this anomaly.

Digging deeper, Dr. Speake analyzed decades of test results from thousands of patients. She saw that there were people who had multiple autoantibodies for several blood draws in a row — and then consistently showed fewer autoantibodies for the next few blood draws.

“We were stunned,” Dr. Speake says. “We spent a lot of time verifying our findings because none of us were convinced at first. But no matter how we sliced and diced the data, it told us the same thing.”

A tiny percentage of patients were experiencing a rare and little understood phenomenon called autoantibody reversion, where somehow one of the autoantibodies disappears.

Dr. Speake and her team also found that “reverters,” people who lose an autoantibody, were significantly less likely to develop T1D in the future — suggesting that they may have some form of “natural protection” from T1D.

But how exactly is that happening?

Graphic Layout Autoantibody Reversion 2
Definition of Reversion: Person who has had two or more autoantibodies over multiple blood draws followed by one or fewer autoantibodies over multiple blood draws.

A Deep Dive Into the Cells

Dr. Speake knew exactly who to team up with to find out: BRI’s Alice Long, PhD, who is an expert in understanding the ins and outs of the immune system. Together, they mapped out a study to investigate this phenomenon.

Alice Long
Alice Long, PhD

Dr. Long is now comparing two sets of immune cell data — one from reverters, the other from people who still have multiple autoantibodies — to see if she can identify differences in their B cells and T cells.

What she discovers could pave the way for new therapies.

“For example, say reverters had more regulatory T cells. We could create an experiment where we boost regulatory T cells and see if reversion might happen in more people,” Dr. Long says.

She and Dr. Speake are still collecting data. But they already have some ideas about how they might build on this work.

“What if there’s an existing immunotherapy drug that targets the pathway we find in people who naturally revert? Could we use it to lower the risk of developing disease in the rest of the population?” Dr. Speake says. “That would be really exciting progress toward BRI’s mission to predict and prevent autoimmune diseases.”

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