Diagnosing Disease Before It Begins, With a Little Help From Your T-cells

Doctors who can do something about your health before you actually get sick sound pretty good. NIAID/MaartjevanCaspel/iStock
Doctors who can do something about your health before you actually get sick sound pretty good. NIAID/MaartjevanCaspel/iStock

Sometimes, doctors are just too late. Whether it's getting a handle on the common cold or something decidedly more dangerous, doctors often need to see how you're feeling first. They need to check your symptoms before they plot a course of action. By that time, you're already sick.

A worldwide team of researchers, led by two professors from Sweden, is trying to remedy that significant ill. They have delved into the genetics of T-cells — those white blood cells that sweep the body for viruses, bacteria and other outside interlopers, then attacks them to keep the body healthy — in an attempt to someday be able to identify diseases before symptoms strike.

That could lead to lower health care costs. A healthier population. It could save lives.

Their study, revealed in a paper titled "A validated gene regulatory network and GWAS identifies early regulators of T-cell associated diseases," was published Wednesday in the journal Science Translational Medicine.

The team involved in the study had one overarching goal: to identify early regulators of disease. That is, to find the genes that "regulate" — turn on or off — other genes that lead to diseases.

If scientists can identify early regulators, they might be able to tip off doctors before symptoms start. They might be able to prevent the symptoms from ever occurring.

Finding those early indicators is a tall order, as the authors admit. Directly detecting an early regulator would require "studies of numerous molecular layers, in numerous cells types, at numerous time-points in 1,000's of healthy individuals over many years," they write in the paper.

Instead, the researchers took a bit of a shortcut, coming up with some diseases that feature long periods of remission. That provided them with a genetic glimpse of a disease both when no symptoms are present and when they are.

Two of the main diseases studied? Multiple sclerosis and seasonal allergic rhinitis (hay fever).

The scientists drilled down to certain proteins that turn genes on and off (called transcription factors, or TFs) to see how they affected the T-cells. "The T-cells can become very different things ... really determined by the transcription," Mika Gustafsson, a lead on the project, says. He and Mikael Benson, another professor at Sweden's Linköping University, are the main authors of the paper.

The authors hit upon certain TFs that proved to be altered from their normal state even when patients were asymptomatic. They found something that told of a disease even before the symptoms struck. They found, in effect, their early regulators.

The study has its limits. For one, it concerns only T-cell associated diseases.

Still, a major part of the work also centers on an analytical strategy that the researchers used to find exactly which early TFs to study. The researchers suggest that method could come in handy in bigger, better studies of other diseases and other cell types.

They specifically point to huge studies like President Obama's Precision Medicine Initiative

The initiative — which will collect health information from thousands of volunteers to form a huge database to study, and which could start as early as 2016 — is still a bit of an audacious dream. But that, in a way, is what the scientists in this study of T-cell diseases were thinking, too.

 "The take home message is that if one could identify the series of process that control T-cell activation," another author of the paper, Sergio Baranzani, a professor in the department of neurology at the University of California San Francisco, says via email, "one would be able to manipulate that process early enough to prevent it or minimize its effect."

And that means doctors who can do something about your health before you actually get sick.