Is Graves’ disease a primary immunodeficiency? New immunological perspectives on an endocrine disease

Abstract

BackgroundUncertainty about factors influencing the susceptibility and triggers for Graves’ disease persists, along with a wide variation in the response to anti-thyroid drugs, currently at approximately 50% of non-responders. The aim of this narrative review is to summarize immunological concepts, with a combined endocrine and immunological perspective, to highlight potential new areas of research.Main textRelevant studies were identified through a systematic literature search using the PubMed and EMBASE databases in March 2016. No cut-offs regarding dates were imposed. We used the terms “Graves’ Disease” or “Basedow” or “thyrotoxicosis” together with the terms “etiology”, “pathophysiology”, “immunodeficiency”, “causality”, and “autoimmunity”. The terms “orbitopathy”, “ophthalmopathy”, and “amiodarone” were excluded. Articles in English, French, German, Croatian, Spanish, and Italian were eligible for inclusion.ConclusionsWhile concepts such as the impact of iodine, smoking, human leucocyte antigen, infections, and ethnicity are established, new ideas have emerged. Pertaining evidence suggests the involvement of autoimmunity and immunodeficiency in the pathophysiology of Graves’ disease. Recent studies point to specific immunological mechanisms triggering the onset of disease, which may also serve as targets for more specific therapies.

Excess iodine intake: sources, assessment, and effects on thyroid function

“…Diffuse goiter may be present due to thyroid hyperplasia, and TSH mimicry stimulates increased liberation of TH . Triggers for the development of autoimmunity of GD are multifactorial and considered having a genetic proponent that may induce sensitivity to environmental factors, including smoking, stress, irradiation, infection, iodine‐containing drug use (e.g., amiodarone), and iodine overload …”

“…176 Triggers for the development of autoimmunity of GD are multifactorial and considered having a genetic proponent 174,177,178 that may induce sensitivity to environmental factors, including smoking, stress, irradiation, infection, iodine-containing drug use (e.g., amiodarone), and iodine overload. [176][177][178][179] In a cross-sectional study comparing iodinedeficient adults in Denmark with adults in Iceland with excessive iodine intakes, the incidence of GD was higher in Iceland, particularly among younger age groups. 138 In Denmark, over 6 years following salt fortification in 1998, the incidence of overt hyperthyroidism increased in younger adults (20−39 years) compared with older age groups (40−59 and >60 years).…”

Basic Immunopathogenic Mechanisms of Autoimmune Thyroid Disorders and Type 1 Diabetes Mellitus

“…Болезнь Грейвса (БГ) -это системное аутоиммунное заболевание, развивающееся вследствие выработки АТ-рТТГ (IgG 1 [1]), клинически проявляющееся поражением щитовидной железы с развитием синдрома тиреотоксикоза в сочетании с экстратиреоидной патологией [9]. Распространенность БГ -от 0,5% до 2%, заболеваемость -1 случай на 4000 населения в год [10].…”

Decreased expression of FcγRII in active Graves' disease patients

“…Graves' disease is a common autoimmune disorder that has a multi‐faced etiology involving genetic and environmental factors and is featured by the presence of thyroid stimulating hormone receptor (TSHR)‐stimulating antibodies (TSAbs) that can promote the function of thyroid follicular cells (TFCs) and stimulate thyroid growth, and thus lead to an overproduction of thyroid hormones (TH) . It is reported that worldwide prevalence of Graves' disease (GD) has become popular with an incidence of 1 in 4000 persons per year . GD has generally been viewed to be mediated by a humoral autoimmune response mainly because the infiltration of lymphocytes can activate the TSHR‐reactive B cells and lead to the abundant production of TSAbs, manifesting as hyperthyroidism …”

“…1 It is reported that worldwide prevalence of Graves' disease (GD) has become popular with an incidence of 1 in 4000 persons per year. 2 GD has generally been viewed to be mediated by a humoral autoimmune response mainly because the infiltration of lymphocytes can activate the TSHR-reactive B cells and lead to the abundant production of TSAbs, manifesting as hyperthyroidism. 3 Anti-TSHR antibodies, as the diagnostic and therapeutic hallmarks of GD, can be found in 90% of GD patients and mainly belong to IgG1 class involved in the early period of humoral response.…”