Autoimmune thyroid disease and rheumatoid arthritis: relationship and the role of genetics
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FRONTIERS IN AUTOIMMUNITY
Autoimmune thyroid disease and rheumatoid arthritis: relationship and the role of genetics Ivica Lazu´rova´ • Ivana Jochmanova´ • Karim Benhatchi Sˇtefan Sotak
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Ivica Lazu´rova´
Springer Science+Business Media New York 2014
Abstract Autoimmune thyroid disease (AITD), known as the most common organ-specific autoimmune disorder, is frequently accompanied by other organ and non-organ-specific autoimmune diseases, including rheumatoid arthritis (RA). Although the exact pathogenic mechanisms of the coexistence of autoimmune disorders are still not completely defined, genetics, immune defects, hormones and environmental factors may play key roles in polyautoimmunity. In this review, the prevalence of AITD and antithyroid autoantibodies in RA patients and rheumatic manifestations in association with thyroid autoimmunity are discussed. Finally, we review the role of genetics in the association of both AITD and RA, especially CTLA-4 and PTPN22 polymorphisms. Keywords
Autoimmune thyroid disease Rheumatoid arthritis Genetics CTLA-4 gene PTPN22 gene
Introduction Autoimmune thyroid disease (AITD) is the most prevalent organ-specific autoimmune disease characterized by the presence of antibodies against thyroid-specific components such as thyroglobulin (aTG), thyroid peroxidase (aTPO), thyrotropin receptor antigen (aTSHr) and sodium iodine symporter (NIS). Currently, AITDs, namely Graves’ disease (GD) and Hashimoto’s thyroiditis (HT), are the most frequent causes of goiters in countries without iodine deficiency with a prevalence of up to 5 % in the general population. However, the prevalence of subclinical disease manifested by the production of antithyroid antibodies (ATA) without clinical manifestation may be even higher [1]. AITD is the result of a complex interaction between genetics and environmental factors [2]. Susceptibility to the production of autoantibodies and thyroiditis is under
I. Lazu´rova´ (&) I. Jochmanova´ K. Benhatchi Sˇ. Sotak 1st Department of Internal Medicine, Medical Faculty, P.J. Sˇafa´rik University, Trieda SNP 1, 04011 Kosice, Slovakia e-mail: [email protected]
independent genetic control, and environmental factors can induce thyroid autoimmunity in genetically susceptible strains of animals (reviewed in [3, 4]). There is evidence that AITD is frequently accompanied by other organ-specific as well as non-organ-specific autoimmune disorders, because there is sharing of genetic and, possibly, environmental factors. These associations are well recognized in the autoimmune polyglandular syndrome, especially type 2, and also in around 4 % of type 1 patients. Clinical recommendations to perform thyroid autoimmunity screening have been made because of its benefit in patients with Addison’s disease, lymphocytic hypophysitis, pernicious anemia, primary biliary cirrhosis, celiac disease and myasthenia gravis [5, 6]. Rheumatoid arthritis (RA) is a chronic, progressive autoimmune systemic disease leading to joint destruction and organ impairment and subseq
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