Scientists from the Endocrinology Research Center of the Ministry of Health of Russia (NMI of endocrinology) investigated the genetic predisposition of Russians to the development of severe autoimmune diseases affecting the endocrine glands (organs that produce hormones) and developed a set of measures for early detection of new diseases. The results of the work were presented at the II interdisciplinary scientific conference “Autoimmune and immunodeficient diseases”. The research is supported by a grant from the Russian Science Foundation (RNF).
Scientists have confirmed the relationship between certain combinations of genes and the development of autoimmune polyglandular syndrome. There were two such combinations: predisposing and protective.
Autoimmune polyglandular syndromes (APS) lead to damage and destruction of normal endocrine gland tissues and the development of autoimmune inflammation. The term “polyglindular” means that the syndrome affects several glands at once, and the word “autoimmune” indicates that the cause of the disease is a malfunction in the work of immunity, as a result of which specific protein compounds, antibodies, instead of protecting the organism, show aggression towards cells of their own thyroid gland, cells that produce insulin in the pancreas (which leads to type 1 diabetes), adrenal cells, gonads. In this case, the work of the glands is suppressed, they produce less hormones, because of what the metabolic processes are violated in the body.
“When interviewing patients with an existing APS, it often turns out that they could not be diagnosed for a long time, to reveal the cause of new manifestations of already existing diseases,” said Anna Larina, co-author of the study, a graduate student of the Department of Endocrinology, NMI. – For example, when a patient has type 1 diabetes, he is given the same dose of insulin as usual, but he suffers from a sharp and severe decrease in blood glucose, which is very dangerous for human health. Such a condition can arise because of a lack of adrenal hormones or an increased function of the thyroid gland. ”
According to the set of glands that affected the autoimmune polyglandular syndrome, four types of this disease are distinguished. The first type manifests itself in childhood and affects the adrenal glands and parathyroid glands (the four glands located on the sides of the thyroid gland, the hormone which controls the exchange of calcium in the body). It is known that this type of APS develops because of the breakdown of the AIRE gene.
The other three types of autoimmune polyglandular syndrome usually appear in 30-40 years. At the same time, women are 3-4 times more likely than men. APS of the second type necessarily includes the defeat of the adrenal glands, to which other pathologies are added. With APS of the third type, adrenal damage does not develop, but the thyroid gland is broken, which starts producing either insufficient or excessive amounts of hormones. The pathology of the thyroid gland is also combined with other autoimmune diseases. APS of the fourth type includes chronic adrenal insufficiency and secondary autoimmune diseases not included in the first, second and third types of APS.
Most often, one component of the disease is manifested first, and before joining of the second and third can take years or even decades, so the type of syndrome is difficult to diagnose correctly right away. Patients with type 2 APS may initially be diagnosed with type 3 APS (the most frequent variant of APS). When they have chronic adrenal insufficiency, which is mandatory for type 2 (this is due to severe stress, infectious diseases or for no apparent reason), the amount of sugar in their blood can drop to life-threatening levels, and if the search for the reasons for such the condition is delayed, a serious complication, capable of causing a lethal outcome, may develop. Because of it, the level of cortisol (stress hormone) in the blood critically decreases, blood pressure drops sharply, nausea starts, repeated vomiting, sharp abdominal pain, and sometimes patients fall into a coma.
Abroad, the genetic factors that are associated with the development of APS are actively studied. For Russians this research was conducted for the first time. Russian scientists collect data on the prevalence of APS among adult Russians and find out what genetic causes can cause it, and what prevent it from developing. They have already confirmed the connection between certain combinations of genes and the development of APS, which is consistent with worldwide practice.
Such combinations turned out to be of two kinds: predisposing (both to the development of APS in general, and to the development of separately chronic adrenal insufficiency, as the most severe of conditions) and protective (protective).
“This site, located on the 6th chromosome, contains a large number of genes associated with the human immune system,” explains Anna Larina. – These gene combinations are risk factors for the development of the disease, which can be realized in this particular patient. In the presence of a single autoimmune endocrine disease, the second develops in 25% of cases, with chronic adrenal insufficiency in 50% of cases. ”
Based on these data, scientists are developing a screening program to identify the risk of developing co-occurring APS components, in particular chronic adrenal insufficiency. For example, if a patient has type 1 diabetes and autoimmune thyroid disease, it is necessary to check whether he has a genetic defense against the development of chronic adrenal insufficiency. If there are no such genes, it is recommended that he regularly check the level of cortisol. This helps to find even a hidden pathology, which has not yet manifested itself clinically. But the combinations of genes predisposing to chronic adrenal insufficiency are less indicative: here, in diagnosis, one must take into account both diabetes mellitus and autoimmune diseases of the thyroid gland, since the genes predictive of the development of these diseases are similar.