b cell autoimmune disease T bet

Researchers Identify Potential Trigger for Autoimmune Disease

Researchers at the National Jewish Health facility in Colorado have identified a cellular process responsible for driving autoimmune reactions. They found that the removal of a transcription factor named T-Bet was responsible for autoimmune-like activation among specific age-related B-Cell (ABCs). By removing T-Bet from B cells in mice, researchers were able to significantly improve lifespan and kidney function.1 These findings suggest a potential new approach for the therapy of autoimmune disorders such as lupus, Chron’s disease, Rheumatoid Arthritis, and?Multiple sclerosis (MS).

Understanding Autoimmunity

Autoimmune disease is considered the third most-prevalent disease in the United States. Such conditions as Chron’s Disease, MS, and Rheumatoid Arthritis all fall within the scope of autoimmune reactions. Currently there are several approaches for the treatment of such conditions, but no cure. Autoimmune disease can be understood simply as the immune system attacking non-threatening cells in our body. Normally, immune reactions are limited to defending against harmful bacteria and other pathogens such as viruses that could do our body harm. In those with autoimmune disorders however, the immune system seems to become confused as to who the ‘bad guys’ are?and just starts attacking everybody! One of the most direct effects caused by such autoimmune dysfunction is the chronic release of compounds known as pro-inflammatory cytokines. As suggested by their name, these compounds lead to the inflammation of tissues within our body and have been tied to nearly every major disease. The involvement of these age-related B cells in the progression of autoimmune disorders has been researched in the past. 2 The new research conducted at the National Jewish Health facility helps to highlight the specifics of how they are involved, and a potential means to mitigate their production of pro-inflammatory cytokines.

Targeting B Cells

Focusing on the involvement of B cells in autoimmunity has been regarded as a potentially fruitful approach for some time. Current research on B cell depletion therapy has provided mixed results, and haven’t been effective in some cases. 3 Other cases however have noted treatments to reduce B cells have provided patients with significant reduction in symptoms for diseases such as Rheumatoid Arthritis and MS.4 These studies typically involve the use of chemotherapy drug Rituximab which targets B cells and causes them to die. Effectively, this lowers the overall activity of B cells in the patients system but has a laundry list of associated side effects including nausea, diarrhea, fever, renal failure, heart attack, and the ever-terrifying Cytokine Storm. This new research suggests a potential means of reducing the activity of B cells without destroying them or inducing tragic side effects. It should still be noted that this type of therapy is a reactive approach not likely well-suited for avoiding the development of autoimmunity in general.

Potential Autoimmune Disease Therapy

There’s no overstating the severity of autoimmune diseases’ impact on modern health. Official numbers provided by the National Institue of Health suggest that as many as 23 million Americans are suffering from autoimmune disease.5 6 It’s likely that these numbers only account for a portion of all disease associated with autoimmune response and that the actual numbers are considerably higher. As noted by Researcher Kira Rubtsova;

“Our previous data demonstrated that T-bet+?ABCs appear in autoimmune patients and in autoimmune-prone mice.?These cells produce high amounts of autoantibodies upon stimulation in vitro, suggesting that they are major precursors of autoantibody-secreting cells.?Moreover, our recent findings indicate that ABCs are very potent antigen-presenting cells and therefore might participate in autoimmune responses by presenting self-antigen to autoreactive T cells”

This highlights how important the ability to control the expression of T-Bet in humans could be to the fight against autoimmune disease. As with all things health, the issue is very complex. Rubstova also notes:

“we found that autoantibodies, spontaneous GCs, and T cell activation occur in [T-Bet disabled]?mice that are more than 7 months old, albeit later than in T-bet?sufficient animals. These data suggest the presence of the alternative, less efficient, T-bet?independent pathway. It is not clear whether this alternative pathway also leads to the development of end-organ damage and death of the animals later in life”?

Simply put; this indicates that even when disabling a certain T-Bet pathway it seems there may be another alternative pathway able to facilitate its production. More research will be needed to first establish the existence of this pathway in humans, and to investigate possible compensatory alternative pathways.

Future Considerations

This research offers exciting promise to those suffering from debilitating autoimmune conditions. If successfully translated into human physiology, these newly identified approaches could offer millions much needed relief. Even if successful however, this type of treatment will still be largely reactionary and not well-suited for the prevention of autoimmune disorders. As illustrated here, Science is slowly deepening our understanding of the dynamics of autoimmune disease?which are very complex. There is considerable amounts of data that suggest diet can have a tremendous impact on the development and progression of autoimmune diseases. One particular area of interest is that of magnesium’s role in autoimmune disease. Many patients suffering from Chron’s disease have been noted as having a magnesium deficiency. Magnesium is a vital nutrient that is involved in hundreds of processes critical to maintaining proper health. There is research suggestive that the use of magnesium supplements may help support the body’s natural immune function in such as way as to help reduce the likelihood of autoimmune disease7