Alopecia Areata (AA) is an autoimmune disorder that is characterized by hair loss on both a patient’s scalp and body. This hair loss can come in the form of patchy hair loss on the scalp (areata, also called AA patchy persistent), total hair loss on the scalp (totalis), and complete loss of all body hair (universalis). While each form of AA is diagnosed separately, the basic mechanism by which the autoantibodies are generated remains the same. Once generated, these antibodies are involved in creating an immune response that eventually attacks a healthy hair follicle, causing irritation of the hair follicle and thus hair loss. The hair follicle, however, is not permanently destroyed and has the ability to re-grow the hair that was once lost. This is especially true in the case of patchy hair loss, as hair can go through cycles of falling out and growing back in, sometimes changing the shape and location of the patches. While there have been some links between AA and other disorders, the majority of patients see no side effects other than hair loss.
Fig 1: Images showing Alopecia Areata (AA pathcy persistent) during multiple stages of of hair loss and regrowth. (Personal Images)
In recent research, there has been a link between oxidative stress and the response of autoantibodies in Alopecia patients. The theory here is that the red blood cells, also known as erythrocytes, of Alopecia patients are subjected to more oxidative stress that can damage proteins and DNA within these red blood cells. One specific consequence of this stress has been noted. The enzyme superoxide disumatse (SOD) is often modified by nitric oxide (NO), which reduces its overall activity. This is important because SOD’s role is to destroy the Reactive Oxygen Species (ROS) that are produced through the normal function of the mitochondria, the source of energy production in cells. Research has shown that antiobodies purified from AA patients have a strong affinity to recognize NO-modified SOD from erythrocytes, pointing to a possible source of initiation or progression of AA.
Fig. 2: A simple representation of oxidative stress (Google Images)
The immune response that results in hair loss has been studied in recent years, and has proved to be very complicated. Researchers have identified a positive feedback loop that results in extensive proliferation of T cells which accumulate at the base of the hair follicle and cause hair loss. Only within the past year has enough information been gathered to produce a useful treatment for AA. Normally, patients were treated in a number of different ways which ranged from experimental steroid injection to the use of over-the-counter hair recovery methods like Rogaine Foam. Most of these treatments, however, proved to be highly ineffective. Interestingly, an existing arthritis medication, Tofacitinib, has been shown to regrow hair in both mouse and human patients by inhibiting a family of proteins called Janus Kinases that are directly involved in the signaling pathway of AA. This is an important step forward that will hopefully result in more effective treatments and a greater understanding of AA and possibly other autoimmune disorders.
good article. easy to understand.
The explanation of where the disease stems and how it presents itself was quite extensive. However, when elaborating on the biological causes for the hair loss, some of the terminology is unclear to an unfamiliar reader. More diagrams of the biological process would be helpful in understanding how this occurs. It was very interesting that an arthritis medication can be the cure to something like this.
This article is well-written and structured nicely. I understood the first and third paragraphs very well. However, I did have to read the second paragraph a few times to grasp the relationships between the red blood cells and SOD, NO, ROS, and the antibodies. That part is still a bit unclear to me so perhaps it could be simplified further, or a illustrative diagram could be included. Overall, the article was interesting and quite comprehensible.
The article is well written. I agree with Melissa a diagram would greatly help illustrate the complexity of the correlation between ROS and the autoantibodies. I think explaining further how the extensive proliferation of T cells comes into play with the ROS and the immune response (autoantibodies) would also help with clarity. It seems as if ROS species are correlated to the immune response which leads to hair loss and also your figure demonstrates that the antioxidant system “outweighs” ROS; is there research suggesting the importance of antioxidants in combating the oxidative stress. Antioxidants seem to be suggested as a potential avenue for treatment (implied importance in Paragraph 2), however of the treatments suggested, it was not demonstrated that treatment is attacking the problem of the ROS. How might the Janus kinases come into play here?
Also, how does accumulation of T cells lead to hair loss? I feel the answer was explained in paragraph two but it might be useful to link T cell accumulation with immune response (with the correlation to ROS) to irritation of the hair follicle to hair loss. A simple but direct sentence, or a diagram, summing up the linear thought process from causes to the result would be greatly helpful here. I really think that your article is very informational and interesting. The first paragraph was great at hooking me in. The second paragraph was dense, but after reading it slowly it did make sense and was interesting and informational. Great read.
Thanks.
Hi Ian, thanks for taking the time to read my report o Alopecia. I appreciate the feedback. I agree with you that there needs to be a bit of clarification in the paragraphs discussing SOD. I suppose I did not include enough information about SOD in fear of losing the non-science reader. SOD’s involvement is interesting in this case because it has been linked to AA, and other autoimmune disorders, but likely does not represent a root cause of these disorders. There has not been research in the field of AA on using antioxidants too reduce oxidative stress in the micro-environment of the hair follicle, but there has been research that linked mutations in SOD and other antioxidant enzymes to AA pathogenesis.
Janus Kinases (JAKs) play a more direct role in AA, and are involved in the positive feedback look that leads to the proliferation of T cells that is alluded to in the final paragraph. They are generally involved in stress signaling and in this case are recruited to the membrane of follicular epithelial cells and CD8+ T cells to initiate the cellular response that leads to transcription of genes to make more CD8+ T cells and to make IFN-gamma, which continues the feedback loop. There is more information on this in the Molecular Basis page. T cells cause hair loss accumulating at the base of the hair follicle and forcing it to prematurely enter the “catagen,” or apoptosis driven, phase. T cells essentially prevent the hair follicle from entering the “anagen,” or growing, phase. This is also explained more in depth in the Molecular Basis section. I hope this was helpful