Interplay of Environmental and Genetic Factors in the Immunologic Mechanisms of Thyroid Autoimmune Diseases
Aim
Description
Autoimmune thyroid diseases (AITD) with their main clinically opposite manifestations as hypothyroidism in Hashimoto’s thyroiditis (HT) and hyperthyroidism in Graves’ disease (GD) are the most common autoimmune disorders. Although both diseases belong to AITD, they are different in pathogenic mechanisms and presentation of the dysregulated immune system. However, both thyroid disorders may coexist in the same individual, being indicative of the presence of mixed Th1/Th2/Th17 immune responses. The prevalence and incidence of autoimmune diseases including AITD has increased significantly over the last decades. In our previous study of iodine deficiency during pregnancy it was revealed that 10.7 % of the 739 pregnant women participating nationwide had elevated thyroperoxidase antibody (TPOAb) levels suggesting preexisting thyroid autoimmunity. Furthermore, when analyzing data concerning thyroid medication use trends from Latvian National Health Service and State Agency of Medicines, there is a steady increase in number of people using thyroxine and thiamazol: thyroid therapy defined daily dose (DDD) per 1000 inhabitants has increased from 10.23 in 2009 to 17.40 in 2017, thereby extremely increasing disease burden on health, health costs, education, society and family life. Therefore, it is critical to investigate and identify the possible interplay of environmental and genetic factors involved in thyroid autoimmunity to propose individualized AITD management strategies since most environmental factors can be modified.
Objectives
- To investigate the association of immune-modulating and selenoprotein genotypes with AITD and related clinical, environmental parameters and T helper pathways.
- To detect whether iodine supplementation improves iodine status in pregnant women with mild iodine deficiency and whether iodine used in combination with selenium will reduce risk of thyroid autoimmunity during pregnancy or postpartum period in women with assessed selenium status and genetic variants.
- To investigate selenium status in patients with AITD and compare it to healthy individuals.
- Analyze patients’ selenium status and compare it to the results of Selenium Intake Scale and genetic variants.
- To investigate the long-term effect of selenium supplementation on the thyroid function and disease activity as well as to evaluate its modulating effects on shifting T helper immune response in treatment-naïve euthyroid patients with HT in context with selenium status and assessed immune-modulating and selenoprotein genetic variants.
- To evaluate the possible association between the number and impact of stressful life events in AITD patients and Th1, Th2, and Th17 circulating cytokine profiles in order to better understand the effects of stress-related mechanisms on the immune system in association with cytokine-related genes.
- Izvērtēt iespējamo saistību starp psihosociālā stresa līmeni AVS pacientiem un Th1, Th2 un Th17 citokīnu profiliem, lai labāk izprastu ar stresu saistīto mehānismu ietekmi uz imūno sistēmu un to korelāciju ar noteiktiem imūnmodulējošiem gēniem.
Results
Urinary iodine concentration, TSH, fT4, anti-TPO antibodies were assessed in pregnant women. In addition serum selenium was measured in 75 of the participants, which was relatively in the normal range. In conclusion, pregnant women in Latvia do not demonstrate a relevant selenium deficiency, however further investigations are required for final conclusions. The correlation of selenium status, iodine deficiency and levels of anti-TPO antibodies was analyzed, as well as the association of these parameters with life-style and dietary habits.
