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The link between baby’s cells and mom’s disease risk

Why does mom’s risk for rheumatoid arthritis skyrocket when her baby has a gene that protects against it?
Microscopic image that shows a male cell inside a female patient
Baby gift: This image of a rheumatoid arthritis nodule shows a male cell (upper left, large round blue nucleus surrounding Y chromosome in green) that presumably traveled from the patient’s baby during pregnancy. Image courtesy of Dr. William Chan

They may grow up and move out of the house, but some part of a mother’s child always stays with her.

And that can be a bad break for mom. 

In a new study, scientists at Fred Hutchinson Cancer Research Center have for the first time identified how the two-way traffic between mom and fetus known as “microchimerism” can sometimes harm mom years later. During this exchange in pregnancy, cells flow back and forth between mother and child. They can take up residence in the other’s body for decades.

The researchers discovered how those fetal immigrants can contribute to mom’s risk of rheumatoid arthritis, a painful autoimmune disease where the body’s immune system attacks its own joints. It turns out some of these alien cells can trigger mom’s immune system to go on the offensive, much like a transplant recipient’s body might reject a donor organ. 

“We’ve known about the association of microchimerism with autoimmune diseases for a long time,” said Dr. Sami Kanaan, the lead researcher on the study and a staff scientist in the lab of microchimerism expert Dr. J. Lee Nelson. “But the why behind this association remained mysterious. Our paper reveals a mechanism related to one particular disease, rheumatoid arthritis.”

The answer solves a paradox identified two years ago by researchers elsewhere: Why does a mother’s risk for rheumatoid arthritis increase when her baby has gene variants that supposedly protect against it?

"We think of the self as being more like an ecosystem. You were never alone."

Dr. J. Lee Nelson

 

When someone has the protective gene variant, they end up with a bit of protein called DERAA. (The letters refer to a sequence of amino acids that make up the protein bit that protects against rheumatoid arthritis.) When you inherit this helpful bit of code from your mom or dad, your immune system will always recognize it as “self” and not react to it. 

But it’s a different story when mom gets cells from her baby with DERAA in them. Her immune system, like that of everyone who wasn’t born with the DERAA sequence, is on the lookout for it. That’s because it just happens to show up in some bacteria and viruses. In fact, roughly two-thirds of bacteria contain it. So our immune systems likely evolved to detect and attack DERAA, thinking it’s a bacterial invader.

If mom’s immune system runs into a fetal cell with DERAA, it starts to rev up. Unfortunately, some proteins in particular locations of the human body, including the joints, also contain the DERAA sequence. With the immune system chronically exposed to microchimerism carrying DERAA, these proteins in the joints can get caught in the crosshairs. The result is inflammation and the painful condition that is rheumatoid arthritis.

By explaining how microchimerism can trigger rheumatoid arthritis, the study could help open the doors to new therapies for the disease, Nelson said. It could also lead to tests that would predict the most severe cases, which could help guide treatment. 

The new study concluded that mothers who carry their child’s DERAA cells are 17 times more likely to develop rheumatoid arthritis. But despite its ability to cause harm, microchimerism can help, too, Nelson and Kanaan note. Years ago, researchers in Nelson’s lab described how pregnant women with rheumatoid arthritis can actually see their symptoms improve. They also found hints that fetal cells can provide protection against breast cancer, and maternal cells can contribute to cells that produce insulin in the child.

Many more mysteries about microchimerism need to be solved. But we can be sure of one thing.

“We often think of ourselves as one discrete individual,” Nelson said. “But really, we all contain cells from others, including our mothers. We think of the self as being more like an ecosystem. You were never alone.”

This study was supported by grants from the National Institutes of Health and the Wong Foundation.  

Jake Siegel, a staff writer at Fred Hutchinson Cancer Research Center, has covered health topics at UW Medicine and technology at Microsoft. He has an M.A. from the Missouri School of Journalism. Reach him at jsiegel@fredhutch.org.

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Last Modified, September 12, 2019