Autoimmunity's Role in Three Endocrine Disorders

Introduction to Autoimmunity and Endocrine Disease

A number of endocrine illnesses are immune-mediated and can now be reliably predicted. Autoimmune disorders can occur both in an individual and in their biological relatives. Families with a history of autoimmunity who have undergone antibody screening become aware of those who carry such risk. Knowing the prevalence of these disorders and the diseases associated with them can help in early diagnosis and prevent conditions from becoming more serious. Autoimmunity affects several glands in the body, and studies reveal that alleles are very important in determining tissue-specific targeting (Aaron W. Michels & George S. Eisenbarth, 2010).

Autoimmunity is necessary for the body to maintain its health by countering the effects of external virulent and organic attacks. It involves regulatory networks that provide the body with immunity against infection. It has not yet been determined why autoimmune processes sometimes become causal in destroying healthy tissues. The autoimmune conditions identified so far range from systemic to tissue-specific disorders, and such conditions can begin at any stage of life — from childhood to adulthood.

The function of the immune system is to protect an individual from infection. With the onset of an autoimmune disease, the immune system launches a misdirected attack on healthy cells. Most of these conditions have a genetic basis. Demographically, women — particularly Hispanic-American, African-American, and Native-American women — face a higher risk of developing certain autoimmune disorders. The disorders develop from a relatively overactive response of the immune system directed at the body's own tissues. Instead of attacking pathogens, the body attacks itself, having confused the cells of a given body part for foreign invaders. The attack may target only particular organs, as is the case with autoimmune thyroiditis, or a particular tissue in several locations, as is the case with Goodpasture's disease, which can affect the basement membrane of both the kidneys and the lungs (Sean Zeelie, 2012).

Autoimmunity in the Endocrine System

The most common autoimmune condition affecting the endocrine system is Hashimoto's thyroiditis (HT). About 10% of the general population is affected by HT. It results in a gradual decline of thyroid function, the development of goiter, and the infiltration of T-cells on histology. The condition is more prevalent among women than men; women are approximately seven times more likely to develop HT. There is no significant association between HT and HLA, even though its occurrence is most likely in genetically susceptible populations. CTLA-4 and thyroglobulin mutations are associated with the condition. T-cells play a critical role in disease pathogenesis, reacting with thyroid antigens and secreting inflammatory cytokines. Autoantibodies accumulate in HT to form TSHR, thyroglobulin, and peroxidase complexes. It is believed that these autoantibodies result from damage to thyroid follicular cells caused by T-cells. Thyroid peroxidase is the main autoantigen, and there is a close association between disease activity and autoantibodies to TPO (Aaron W. Michels & George S. Eisenbarth, 2010).

Evidence exists for the presence of genetic components in most cases of autoimmune endocrine diseases. Studies of familial inheritance of thyroiditis and type 1 diabetes have yielded some of the strongest evidence. The concordance rate among siblings is approximately 3% to 4%, while the rate among monozygotic twins is about 50%. Compared to the risk in the general population, which is approximately 0.3%, both groups face a significantly elevated risk. This elevated risk, as the data indicate, is attributable to genetic as well as environmental factors (Mark S. Anderson, 2008).

Graves' Disease and Addison's Disease

Evidence shows that when an individual develops type 1 diabetes, their risk of contracting other autoimmune diseases increases. This is due to the genetic susceptibility that accompanies such a condition. The autoimmune process occurring in pancreatic cells may also affect other organs, leading the individual to develop organ-nonspecific autoimmune conditions. Graves' disease and Hashimoto's thyroiditis are the most frequently occurring comorbidities in type 1 diabetes (15–30%). Others include celiac disease (4–9%), Addison's disease (0.5%), vitiligo (2–10%), and autoimmune gastritis (5–10%). Type 1 diabetes patients who develop additional autoimmune diseases experience a reduction in quality of life and increased mortality and morbidity (Aleksandra Krzewska & Iwona Ben-Skowronek, 2016).

As with various other autoimmune conditions, Graves' disease results primarily from a combination of environmental and genetic factors that may also influence the condition's long-term prognosis. Over time, disease activity may fluctuate, and patients may periodically become euthyroid. Beyond this variation, it has been established that hyperthyroidism therapy can influence the activity of the disease (Peter Laurberg et al., 2008). Autoimmune adrenal insufficiency results from the destruction of the adrenal cortex through cell-mediated immune activity.

Addison's disease can also emerge within autoimmune polyendocrinopathy syndromes. When type 1 diabetes mellitus and/or thyroid disease occur together with Addison's disease, the condition is referred to as autoimmune polyglandular syndrome type 2 (APS-2). APS-2 rarely occurs in children, and there is insufficient data for a comprehensive study of this population (Heves Kirmizibekmez, Rahime Gul Yesiltepe Mutlu, Nafiye Demirkiran Urganci & Ayse Oner, 2015).

Conclusion

While there are many aspects still not yet fully explored and understood, an ever-increasing body of evidence points to a significant role that epigenetically modified gene expression plays in autoimmunity development. Research conducted in the past employed methods that have since been surpassed by new technologies, including next-generation sequencing, which is capable of increasing the clarity and detail of data derived from epigenetic modifications. Nonetheless, improving our understanding of the role epigenetic modifications play in autoimmunity development has the potential to bring closer the possibility of preventing or controlling autoimmune disease through the use of drugs targeting proteins that regulate DNA methylation, chromatin modifications, and various other epigenetic mechanisms.

References

Aaron W. Michels, & George S. Eisenbarth. (2010). Immunologic endocrine disorders. Journal of Allergy and Clinical Immunology, 225–237.

Aleksandra Krzewska, & Iwona Ben-Skowronek. (2016). Effect of associated autoimmune diseases on type 1 diabetes mellitus incidence and metabolic control in children and adolescents. BioMed Research International.

Heves Kirmizibekmez, Rahime Gul Yesiltepe Mutlu, Nafiye Demirkiran Urganci, & Ayse Oner. (2015). Autoimmune polyglandular syndrome type 2: A rare condition in childhood. Journal of Clinical Research in Pediatric Endocrinology, 7(1), 80–82. doi:10.4274/jcrpe.1394

Kohei Kaku. (2010). Pathophysiology of type 2 diabetes and its treatment policy. Japan Medical Association Journal, 41–46.

Mark S. Anderson. (2008). Update in endocrine autoimmunity. Journal of Clinical Endocrinology and Metabolism, 3663–3670.

Peter Laurberg, Goran Wallin, Leif Tallstedt, Mirna Abraham-Nordling, Goran Lundell, & Ove Torring. (2008). TSH-receptor autoimmunity in Graves' disease after therapy with anti-thyroid drugs, surgery, or radioiodine: A 5-year prospective randomized study. European Journal of Endocrinology, 69–75.

Sean Zeelie. (2012). Understanding autoimmune disease: A review article for the layman. Research Centre for Autoimmune Disease.