Antibodies to 'second colloid antigen'. A study on the prevalence in sporadic forms of congenital hypothyroidism

Abstract

Antibodies against the so called 'second colloid antigen' (CA2 antibodies) occurred in 51% of the mothers of hypothyroid children detected by screening for neonatal congenital hypothyroidism in Quebec (N = 49) and in The Netherlands (N = 26). In The Netherlands where corresponding neonatal serum was available, 31% (8 of 26) of the infants with congenital hypothyroidism were positive for antibodies against the second colloid antigen. When during follow-up, 3 to 5 years after diagnosis, the mothers and their children were investigated, 46% (7 of 15) of the mothers were positive for antibodies against the second colloid antigen, whereas 29% (4 of 14) of the hypothyroid children were also positive. Various control groups did not show more than a 12% positivity. This presence of thyroid-reactive antibodies in a proportion of the hypothyroid children 3 to 5 years after diagnosis is not compatible with a mere transplacental passage; it indicates that the antibodies must be produced by the mothers and by the children themselves. We conclude that a thyroid autoimmune response occurs in a considerable part of infants with congenital hypothyroidism and their mothers and that this immune response seems to persist in both of them for years.In 1985 were reported the presence of immunoglobulins (Igs) blocking TSH-induced thyroid growth in the sera of about 50% of mothers giving birth to infants with sporadic congenital hypothyroidism (CH). Sera of the infants also contained the growth blocking Igs (1,2). These results suggested a trans¬ placental passage of maternal Igs influencing TSHinduced processes of thyroid growth which might be important in the pathogenesis of sporadic CH. Later Peters et al. (3) and recently Bogner et al. (4) also reported the presence of thyroid-reactive Igs in sera of CH children and their mothers; they de¬ scribed both growth blocking, in approximately 50% of maternal and infant sera, and thyroid cyto¬ toxic antibodies, in approximately 25% of maternal and infant sera. As early as in 1961 Balfour et al. (5) demonstrated an autoimmune involvement in CH.These authors discovered a new kind of thyroid autoantibodies directed towards a colloidal antigen, called 'second colloid antigen' (CA2). They showed in absorption and precipitation experi¬ ments that these antibodies were distinct from autoantibodies against the first colloidal antigen, thyroglobulin. CA2 antibodies were found in the sera of 4 out of 11 mothers of'athyreotic cretins' as well as in sera of patients with nowadays well estab¬ lished thyroid autoimmune disorders such as Ha¬ shimoto's thyroiditis (95-100%), atrophie thyroiditis (35-45%) and Graves' disease (40-50%).Since the initial report of Balfour et al., the antigen specificity and clinical relevance of CA2 antibodies have only scarcely been studied. Yet it has become clear that CA, antibodies are not pres¬ ent only in well-established thyroid autoimmune diseases but that they also occur in de Quervain's subacute thyroiditis. In this putatively viral disor-

Autoantibodies with Different Level of Specificity and Functionality in the Pathogenesis and Diagnostics of Autoimmune Thyroid Disorders

“…д. ), а так же к хит шоковым протеинам (шаперонам) [47]. Та ким образом, главная особенность аутоиммунных заболеваний ЩЖ -это продукция широкой палит ры ауто АТ, в том числе антитиреоидных, патоген ный потенциал которых до сих пор полностью не ус тановлен.…”

Autoantigens in thyroid diseases

“…11), previously shown to recognise the epitope containing T4 at position 2553 on the Tg molecule. It is still not known what triggers autoimmunity, and environmental agents such as viruses [67,94] and bacteria have previously been implicated in the induction of thyroid autoimmunity. Aberrant surface class II expression has been demonstrated on human [37] thyrocytes and class II § thyrocytes have been shown to stimulate thyrocytespecific T cell clones [54].…”