Transcription Factor T-Bet Triggers MS, Other Autoimmune Diseases, Study Finds

Transcription Factor T-Bet Triggers MS, Other Autoimmune Diseases, Study Finds

The expression by immune B-cells of a protein called T-bet is crucial to promoting production of autoantibodies that recognize and destroy the tissues of one’s own body, finds a new study by researchers at National Jewish Health in Denver.

The study, “B cells expressing the transcription factor T-bet drive lupus-like autoimmunity,” appeared in the Journal of Clinical InvestigationIt not only identifies a trigger for autoimmunity, but also suggests a new potential therapeutic target to prevent autoimmune diseases such as multiple sclerosis (MS) and lupus that strike women two to 10 times as often as men. Overall, about 80 percent of autoimmune patients are women.

Previous studies showed that a subset of immune B-cells known as age-related B-cells (ABCs) expresses the T-bet transcription factor, which controls the expression of genes. Interestingly, these ABCs were found to appear in patients with autoimmune diseases and in autoimmune experimental animal models, suggesting that they may play a role in such diseases.

Through genetic manipulation, researchers created autoimmune-prone mice that did not express the T-bet protein. Evaluating the immune cell subsets these mice had in circulation confirmed the absence of ABCs. Researchers weren’t surprised, since these cells require T-bet expression to survive. Strikingly, these mice showed reduced signs of autoimmune disease, they lived longer, and their production of autoantibodies was delayed compared to mice that did express T-bet and had ABCs.

“Our findings confirm that Age-associated B Cells (ABCs) drive autoimmune disease,” National Jewish Health biomedical science instructor Kira Rubtsova and the study’s lead author, said in a press release. “We demonstrated that the transcription factor T-bet inside B cells causes 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.”

These results indicate that T-bet expression in B-cells is key the autoimmunity process, contributing to its development or progression.

“Our findings for the first time show that ABCs are not only associated with autoimmune disease, but actually drives it,” said Rubtsova, concluding that targeting T-bet-expressing B cells may therefore be a potential therapeutic strategy for autoimmune diseases.


    • Alice Melão says:

      I can totally understand this may not seem much, but in such a complex disease as MS knowing and understanding every small detail can make all the difference. New improved and more efficient treatments may come from these ‘tiny’ biological details.

      • cheryl Turow says:

        As a lay person my understanding is both Rituxan and Ocrevus target and remove B cells, slowing down the progression of MS. Not a cure, but this knowledge is a positive start for sufferers!

  1. Sandy Thomas says:

    Severe Autoimmune has also been found as a side effect in ALS patient that is being treated with the drug masitinib.

    Autoimmune-like hepatitis during masitinib therapy in an amyotrophic lateral sclerosis patient

    Published online 2015 Sep 28.
    World J Gastroenterol


    We report a case of acute severe hepatitis resulting from masitinib in a young amyotrophic lateral sclerosis patient. Hepatotoxicity induced by masitinib, a tyrosine kinase inhibitor, is usually transient with mild elevation of transaminases, although acute hepatitis has been not reported to date. The hepatitis was resolved after masitinib was discontinued and a combination of prednisone and azathioprine was started. The transaminases returned to baseline normal values five months later. This is the first case in the hepatitis literature associated with masitinib. The autoimmune role of this drug-induced liver injury is discussed. Physicians should be aware of this potential complication.

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