Though no universal pathogenesis is accepted, the most popular mechanism behind the onset of alopecia areata is believed to be the theory of immune privilege collapse. Certain areas of the body including the central nervous system, the testis, the hair follicle and parts of the eye are considered to be immune privileged. These areas are unique due to many factors that downreguulate immune system cells. Under normal conditions the hair follicle itself is considered MHC class I negative, indicating it cannot present antigens to the MHC I molecule. (Paus, 2003) This MHC class I molecule is necessary for the activation of T cells in the immune response during pathogenic invasion. However, the upregulation of genetic factors involved with inflammatory immune response or environmental stressors can induce an unregulated secretion of pro inflammatory cytokines. These cytokines recruit MHC class I molecules to the hair follicle where self proteins are presented to T cells. This now unregulated presentation stimulates the activation of cytotoxic T cells that then recognize the hair follicle as a pathogenic intruder and induces phagocytosis.
The unregulated release of pro-inflammatory cytokines found in this immune privilege collapse is believed to share a link with many other inflammatory diseases such as cardiovascular disease. Recent studies have utilized rodent models with alopecia areata to demonstrate the exacerbating effects this disease has on stress coping mechanisms within the body. Stress hormones involved in the HPA pathway including ACTH and cortisone were found to be significantly elevated in those rodents exhibiting AA compared to control rodents. Additionally, stress hormone receptors in the brain were upregulated in AA rodents, explaining the increased stress response in these rodents. The elevated stress hormones found within AA rodents combined with a chronic production of pro-inflammatory cytokines can result in additional detrimental effects throughout the body.
The study revealed that cardiac hypertrophy resulted from the chronic release of pro-inflammatory agents in AA rodents. The heart mass was found to be significantly greater, yet had a significantly less number of nuclei in atria of AA rodents compared to the control. This suggests that morphological changes occurred in the muscle of the heart, resulting in a gain in muscle tissue. However, the contractibility of the heart did not necessarily increase. In fact, an increase in collagen was found in AA rodents heart which quickly accumulates in peripheral blood vessels and causes restricted blood flow. The resulting hypertension applies even greater stress on the heart to pump blood throughout the body, eventually causing cardiac tissue damage. (Wang, 2013)
Though not entirely linked to the physiological stress response, there is significant evidence to suggest stress is one of the many contributing factors of alopecia areata. This combined with a genetic predisposition leads to an inappropriate immune response that can ultimately contribute to a wide range of chronic inflammatory diseases. Thus, autoimmune related baldness is yet another example of the harmful consequences that can result from prolonged stressors in our daily lives.
Kang, H., Wu, W., Lo, B., Yu, M. Leung, Gl, Shapiro, J., McElwee, K. 2010. Hair follicles from alopecia areata patients exhibit alterations in immune privilege- associated gene expression in advance of hair loss. Journal of Investigative Dermatology [Internet]. [Cited 2013 Nov 29]130(11): 2677-2680.
Paus, R., Ito, N., Takigawa, M., & Ito, T. (2003). The Hair Follicle and Immune Privilege. Journal Of Investigative Dermatology Symposium Proceedings, 8(2), 188.
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