Researchers identify trigger for autoimmune disease

Newly identified cells help explain why women are diagnosed with autoimmune disease more often than men.
By Amy Wallace   |   Updated May 11, 2017 at 10:50 AM
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May 11 (UPI) -- Researchers at National Jewish Health have identified age-associated B cells as a trigger for autoimmune diseases like lupus and Crohn's disease.

Autoimmune diseases happen when the immune system attacks and destroys the organs and tissue of its own host. There are numerous autoimmune diseases, which impact millions of Americans.

Certain autoimmune diseases like lupus, rheumatoid arthritis and multiple sclerosis affect women two to 10 times more often than men. Nearly 80 percent of autoimmune patients overall are women.

The research shed light on why women are diagnosed with autoimmune disease more often than men.

Researchers previously identified a subset of B cells that accumulate in autoimmune patients, and elderly female mice and mice with autoimmune diseases.

The subset of B cells was named Age-associated B cells, or ABCs, and subsequent research showed the transcription factor T-bet plays a crucial role in the appearance of ABC. Transcription factors bind to DNA inside cells and drive the expression of genes.

T-bet is seen inside cells when a combination of receptors on B-cell surfaces known as TLR7, interferon-gamma and B-cell receptor are stimulated.

"Our findings confirm that Age-associated B Cells [ABCs] drive autoimmune disease," Kira Rubtsova, an instructor in biomedical science at National Jewish Health, said in a press release. "We demonstrated that the transcription factor T-bet inside B cells cause ABCs to develop. When we deleted T-bet inside B cells, mice prone to develop autoimmune disease remained healthy. We believe the same process occurs in humans with autoimmune disease, more often in elderly women."

Researchers were able to eliminate the ability of autoimmune-prone mice to express T-bet inside B cells, resulting in ABCs that did not appear and healthy mice. Roughly 80 percent of mice with T-bet in B cells and 20 percent of T-bet deficient mice had kidney damage.

"Our findings for the first time show that ABCs are not only associated with autoimmune disease, but actually drive it," Rubtsova said.

The study was published in the Journal of Clinical Investigation.

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