Autoimmune thyroid disease (AITD) is the most common organ specific
autoimmune disorder usually resulting in dysfunction (hyperfunction,
hypofunction or both) of the thyroid gland. The syndromes comprising
autoimmune thyroid disease are many intimately related illnesses: Graves?
disease with goitre, hyperthyroidism and, in many patients, associated
ophthalmopathy, Hashimoto?s thyroiditis with goitre and euthyroidism or
hypothyroidism but also thyroid dysfunction occurring independently of
pregnancy and in 5-6% of postpartum women and thyroiditides induced by
different drugs and other environmental influences. The immunological
mechanisms involved in these diseases are closely related, while the
phenotypes probably differ because of the specific type of immunological
response that occurs. The syndromes are connected together by their similar
thyroid pathology, similar immune mechanisms, co-occurrence in family groups,
and transition from one clinical picture to another within the same
individual over time. In some patients, other organ specific and nonorgan
specific autoimmune syndromes are associated with autoimmune thyroid disease,
including pernicious anemia, vitiligo, myasthenia gravis, primary adrenal
autoimmune disease, celiac disease, rheumatoid arthritis or lupus. Thyroid
peroxydase, TPO, the primary enzyme involved in thyroid hormonogenesis, was
initially identified in 1959 as the ?thyroid microsomal antigenn. It is
uncertain whether TPO autoantibodies or TPO-specific T cells are the primary
cause of thyroid inflammation, which can lead, in some individuals, to
thyroid failure and hypothyroidism. TPOAbs are the hallmark of AITB and are
present in almost all patients with Hashimoto?s thyroiditis, in two-thirds of
patients with postpartum thyroiditis and also in 75% of patients with Graves?
hyperthyroidism. The antibodies are mainly produced by lymphocytic infiltrate
in the thyroid gland and only to a small extent by regional lymph nodes or
the bone marrow. Unlike antibodies against thyroglobulin (Tg), TPO antibodies
are capable of inducing antibody-dependent cell-mediated cytotoxicity.
Antibodies to TSH?R mimic the function of TSH, and cause disease by binding
to the TSH?R and stimulating (or inhibiting) thyroid cells. The TSHR, a
member of the G protein?coupled receptor family with seven membrane- spanning
segments. Patients with autoimmune thyroid disease may have both stimulating
and blocking antibodies in their sera, the clinical picture being the result
of the relative potency of each species; blocking antibodies seem more common
in Graves? patients with ophthalmopathy compared to those without this
complication. The major T cell epitopes are heterogeneous and T cell
reactivity against certain TSH-R epitopes has been present in high proportion
in normal subjects. More diversified response to TSH-R, with heterogeneity of
epitope recognition by TSAb, is predictive of likely remission after
antithyroid drug treatment for Graves? disease.
Association of the T-cell regulatory gene CTLA4 with Graves’ disease and autoimmune thyroid disease in the Japanese
