IgA class and subclass thyroid auto-antibodies in Graves' disease and Hashimoto's thyroiditis

The reported prevalence of IgA class thyroid antibodies in Hashimoto's thyroiditis is variable and the IgA subclass distribution in unknown, despite recent reports of IgG subclass restriction in the thyroid auto-antibody response. Using an ELISA, IgA class antibodies were found against thyroglobulin (Tg) and microsomes (Mic) in 40-52% of patients with Graves' disease and Hashimoto's thyroiditis, and, against thyroglobulin, they were detected in the absence of IgG antibodies in 10% of the cases. Both IgA1 and IgA2 subclasses were detected in all patients with IgA class antibodies, although a significantly higher proportion of IgA2 relative to IgA1 was found in microsomal compared with thyroglobulin antibodies. In view of the high turnover rate and unique complement-fixing properties of IgA2 antibodies, this class of thyroid auto-antibody may play an important role in determining the response in thyroid auto-immunity.     

Autoantibodies highly increased in patients with thyroid dysfunction

To evaluate the significance of antithyroid antibodie levels, five hundred and twenty-six patients with thyroid diseases and 292 health subjects from Yuci district, Shanxi province, China, were studied. Serum levels were determined for thyroid hormone receptor antibody （TRAb）, microsomal antibody （TMAb） and thyroglobulin antibody （TGAb）. Among patients, the percentages for nodular goiter and thyroid adenoma, Graves＇ disease, and Hashimoto＇s thyroiditis are 44.1%, 19.6% and 17.7%, respectively. The ratios of female to male were 2.0 to 15.6. Antibody-positive patients for TMAb, TGAb and TRAb were detectable as 94.6%, 76.3% and 20.4% for Hashimoto＇s thyroiditis, and 40.0%, 30.0% and 90.3% for Graves＇s disease. In conclusion, the high levels of the TRAb in Graves＇ disease, and those of the TGAbFFMAb in Hashimoto＇s thyroiditis and idiopathic hypothyroidism are meaningful for characterizing the epidemiological basis of the diseases and for using as prognostic indicators for the relapse in individual patients. Cellular ＆ Molecular Immunology.     

The CD40, CTLA-4, thyroglobulin, TSH receptor, and PTPN22 gene quintet and its contribution to thyroid autoimmunity: back to the future

Autoimmune thyroid diseases (AITD) are common autoimmune diseases, affecting up to 5% of the general population. Thyroid-directed autoimmunity is manifested in two classical autoimmune conditions, Hashimoto's thyroiditis, resulting in hypothyroidism and Graves' disease resulting in hyperthyroidism. Autoimmune thyroid diseases arise due to an interplay between environmental and genetic factors. In the past decade significant progress has been made in our understanding of the genetic contribution to the etiology of AITD. Indeed, several AITD susceptibility genes have been identified. Some of these susceptibility genes are specific to either Graves' disease or Hashimoto's thyroiditis, while others confer susceptibility to both conditions. Both immunoregulatory genes and thyroid specific genes contribute to the pathogenesis of AITD. The time is now ripe to examine the mechanistic basis for the contribution of genetic factors to the etiology of AITD. In this review, we will focus on the contribution of non-MHC II genes.     

Lymphocyte blastogenic response to human thyroglobulin in Graves' disease, Hashimoto's thyroiditis, and metastatic thyroid cancer.

In view of the past contradictory reports concerning in vitro lymphocyte transformation induced by human thyroglobulin (Tg) in thyroid diseases, the present study was undertaken to re-examine the response using improved methods in cell separation, culture, and cell harvesting. It has been found that the optimal dose level of Tg for maximal blastogenesis in culture differs from patient to patient. Consequently, it is inappropriate to use a single dose level of Tg for evaluation of the blastogenesis in study groups. By using serial Tg dose levels of 0.5 through 30 micrograms/ml in cultures, it was found that that incidence of positive responders in Graves' disease was 69.2%, in Hashimoto's thyroiditis 71.4%, and in healthy controls 9.1%. Metastatic thyroid cancer patients responded in a 50% incidence. All of the positive responders in the cancer group had elevated Tg levels, but no anti-Tg antibody in their sera.     

Clinical value of a bispecific antibody binding to thyroglobulin and thyroperoxidase (TGPO-aAb) in various thyroid diseases.

TGPO-aAb is a bispecific antibody which binds to thyroglobulin as well as thyroid peroxidase. It is supposed to be raised in some patients with autoimmune thyroid disease. We investigated 205 patients suffering from Graves' disease (n = 81), Hashimoto's thyroiditis (n = 36), toxic nodular goitre (n = 50), differentiated carcinoma of the thyroid (n = 10), and autoimmune thyropathy of unknown origin (n = 28). An immunoradiometric assay was used to measure serum TGPO-aAb. Eighty-nine of 205 patients had elevated titres of TGPO-aAb. If TGPO-aAb were raised then autoantibodies against thyroglobulin and thyroid peroxidase were always raised, too. This was, however, not true vice versa. We found TGPO-aAb in 61% of patients with Hashimoto's, 49% of patients with Graves', 64% of patients with autoimmune thyropathy, but only in 12% of patients with toxic nodular goitre. In patients with thyroid carcinoma TGPO-aAb was found only if there was evidence of paraneoplastic autoimmune thyroiditis. We re-examined 16 of 36 patients with Hashimoto's thyroiditis after 1 year: 8 patients had retained their raised TGPO-aAb, 4 patients showed no TGPO-aAb on both occasions, and 4 patients had 'lost' their previously raised TGPO-aAb on follow-up. We conclude that TGPO-aAb may provide additional information in Hashimoto's thyroiditis. Determination of TGPO-aAb does not allow to distinguish between various forms of autoimmune thyroid disease. Nevertheless, the presence of TGPO-aAb and its variation during the natural course of autoimmune thyroid disease remains to be understood which would give a better insight into its clinical significance.     

Autoantibodies to p53 in sera of patients with autoimmune thyroid disease

Mutations in the tumor suppressor gene, p53, lead to intracellular accumulation of abnormal p53 protein and are associated with p53 autoantibodies. p53 also accumulates in autoimmune diseases and Hashimoto's thyroiditis, but it is unknown if p53 autoantibodies occur in the latter. We measured p53 autoantibodies in the sera of 93 patients with thyroid disease and 19 patients without thyroid disease. Anti-p53 antibodies were detected in the sera from 4.2% (2/48) of patients with autoimmune thyroid disease, including one patient with Hashimoto's thyroiditis (3.7%, 1/27) and one with Graves' disease (4.8%, 1/21). A third patient with pseudohypoparathyroidism, but without thyroid disease, was also positive (1/19; 5.2%). None of 19 patients with differentiated thyroid cancer had anti-p53 antibodies. We conclude that anti-p53 antibodies can be detected in the sera from approximately 4% of patients with autoimmune thyroid disease. This finding suggests that increased DNA damage and apoptosis may be associated with autoimmune thyroid disease.     

Lymphoepithelial lesion in the thyroid. A non-specific histological finding

In order to assess the specificity of lymphoepithelial lesion (LEL) in the diagnosis of thyroid lymphoma, the thyroid glands of patients with Hashimoto's disease, lymphoid infiltrates in the vicinity of papillary carcinoma, focal thyroiditis in Graves' disease and malignant lymphoma of the thyroid were studied by conventional pathological and immunohistochemical techniques using a panel of antibodies against epithelial cells (CAM 5.2) and leucocytes (LCA, pan-T, and pan-B antisera). LEL was encountered in all cases. In cases of peritumoral lymphoid infiltrates LEL represented a focal phenomenon, whereas in Hashimoto's and Graves' diseases and lymphoma, it was found in multiple areas. In cases of malignant lymphoma LEL was encountered in the vicinity of areas where diffuse parenchymal destruction by tumor cells had occurred. The results suggested that although LEL is almost always present in lymphomas it can also be encountered in other diseases of the thyroid. If therefore LEL has no diagnostic specificity, the diagnosis of malignant lymphoma must be supported by other histological findings.     

Fas ligand gene polymorphisms are not associated with Hashimoto's thyroiditis and Graves' disease

Hashimoto's thyroiditis and Graves' disease represent the two most common autoimmune thyroid disorders. Whereas in Hashimoto's thyroiditis FasL expression causes thyrocytes to undergo apoptosis, additional anti-apoptotic molecules appear to protect these cells in Graves' disease. Mutations of the FasL gene were observed in systemic lupus erythematosus. Given its functional relevance for the pathogenesis of thyroid autoimmunity we wondered whether variants of the FasL gene play a role in Hashimoto's thyroiditis and Graves' disease. We genotyped families with at least one offspring affected by Hashimoto's thyroiditis (n = 86) and Graves' disease (n = 90) for two FasL gene polymorphisms (C -843 T in the promoter, A IVS2nt-124 G in intron 2). Extended transmission disequilibrium (ETDT) and chi(2) testing were performed. Neither polymorphism alone nor the promoter/intron 2 haplotypes (p = 0.91) were associated with Hashimoto's thyroiditis. No association with Graves' disease was observed for the promoter polymorphism (p = 0.91) and the intron 2 "A" allele (57.1%; p = 0.36) or the promoter/intron 2 haplotypes (p = 0.31). Moreover, intron 2 genotyping revealed no difference between an additional 251 patients with Graves' disease and 197 healthy controls (p = 0.37). Italian and German families did not differ for the studied polymorphisms. In conclusion, our data do not suggest common genetic FasL variants to significantly contribute to the pathogenesis of either Hashimoto's thyroiditis or Graves' disease.     

Lymphocyte transformation with thyroglobulin in thyroid diseases

The lymphocyte transformation test (LTT) with thyroglobulin was correlated with humoral thyroglobulin antibodies (TGA) in different thyroid diseases. All patients with significant TGA had a positive LTT, while two LTT positive patients either had no TGA or revealed them a few weeks later. Lymphocyte transformation was found in all investigated cases of chronic thyroiditis and Hashimoto's disease, half of the patients with multinodular goitres and Graves' disease, and some cases (five out of sixteen) of simple goitres.     

Heterogeneity of thyroid autoantigens identified by immunoblotting

Autoimmune thyroid disease in man is commonly associated with autoantibodies against thyroglobulin, microsomes, and the TSH receptor, and the character and specificity of these antithyroid antibodies have been extensively utilized in investigating these conditions. In the present study we have asked whether other thyroid-related antigens exist, against which autoantibodies may be directed. A crude thyroid extract was separated by polyacrylamide gel electrophoresis followed by immunoblotting with serum obtained from patients with Graves' disease or Hashimoto's thyroiditis. Antibodies in sera from patients with Graves' disease and Hashimoto's thyroiditis reacted with many antigenic determinants in immunoblots of the thyroid membrane preparation (2000g supernatant). These determinants were disease specific in that sera from normals and patients with Addison's disease and rheumatoid arthritis did not react, but there was no difference between the patterns of reactivity with Graves' disease or Hashimoto's thyroiditis sera. Thyroglobulin produced two predominant bands of reactivity at 320 and 200 kDa, whereas purified microsomal antigen produced a triplet of bands around 105 kDa, when these preparations were reacted with appropriate autoimmune sera. Nonetheless, some sera produced additional bands with the microsomal antigen blots, indicating that some of the antigens which were detected using crude thyroid membrane remained in the microsome preparation to produce multiple antibody binding reactivities. We were unable to inhibit any of the antibody binding with TSH. Purification of individual thyroid antigens on the basis of their molecular weights should standardize current antibody assays and permit more detailed evaluation of the cellular immune responses in Graves' disease and Hashimoto's thyroiditis.     

Antibodies that promote thyroid growth. A distinct population of thyroid-stimulating autoantibodies

We used a strain of differentiated rat-thyroid cells in continuous culture (the FRTL-5 strain) to detect the presence of growth-promoting antibodies in serum samples from patients with autoimmune thyroid disease. We found that IgG preparations from 17 of 20 patients (85 per cent) with active Graves' disease and two of five patients (40 per cent) with Hashimoto's thyroiditis could augment thyroid-cell growth. In parallel with IgG-induced elevations in intracellular cyclic AMP levels in the same cell line, all 20 of the patients with active Graves' disease had thyroid-stimulatory antibodies. Patients' IgG preparations fell into three subclasses: those with both potent cyclic AMP stimulation and potent growth-promoting activity; those with potent cyclic AMP stimulation but low-level growth promotion; and those with potent growth promotion and low-level cyclic AMP action. Growth-promoting antibodies were not detected in patients with Graves' disease in remission (seven patients), nodular goiter (seven), subacute thyroiditis (five), or atrophic thyroiditis (one). Simultaneous assays of growth promotion and cyclic AMP stimulation may be useful in the care of patients with autoimmune thyroid disease.     

Serological evidence for the role of bacterial infections in the pathogenesis of thyroid diseases

Subacute thyroiditis is generally believed to be of viral origin, and infection is also suspected of playing a role as a triggering factor in the pathogenesis of autoimmune thyroid diseases. We have measured a broad spectrum of bacterial and viral antibodies in paired sera of 32 patients with thyroid disease of recent onset. The data indicate a preceding infection in 14 (44%) of the patients, enterobacterial in 5, streptococcal in 4 and staphylococcal in 2. A viral infection was suggested in 6 patients, in each case caused by different agents; 3 of them also showed evidence of a bacterial infection. Patients with positive microbial serology were found in all diagnostic groups, including subacute thyroiditis, Graves' disease and Hashimoto's disease. These results suggest an association between a preceding bacterial infection and the development of thyroid disease in some patients.     

Susceptibility genes in thyroid autoimmunity

The autoimmune thyroid diseases (AITD) are complex diseases which are caused by an interaction between susceptibility genes and environmental triggers. Genetic susceptibility in combination with external factors (e.g. dietary iodine) is believed to initiate the autoimmune response to thyroid antigens. Abundant epidemiological data, including family and twin studies, point to a strong genetic influence on the development of AITD. Various techniques have been employed to identify the genes contributing to the etiology of AITD, including candidate gene analysis and whole genome screening. These studies have enabled the identification of several loci (genetic regions) that are linked with AITD, and in some of these loci, putative AITD susceptibility genes have been identified. Some of these genes/loci are unique to Graves' disease (GD) and Hashimoto's thyroiditis (HT) and some are common to both the diseases, indicating that there is a shared genetic susceptibility to GD and HT. The putative GD and HT susceptibility genes include both immune modifying genes (e.g. HLA, CTLA-4) and thyroid specific genes (e.g. TSHR, Tg). Most likely, these loci interact and their interactions may influence disease phenotype and severity.     

Expression of intercellular adhesion molecule-1 (ICAM-1) on thyroid epithelial cells in Hashimoto's thyroiditis but not in Graves' disease or papillary thyroid cancer.

In order to study the possible role of antigen-independent adhesion systems in thyroid autoimmunity, we evaluated by indirect immunofluorescence the expression of lymphocyte functional antigen-1 (LFA-1) and its ligand ICAM-1 on mononuclear cell infiltrates (when present) and thyroid follicular cells of four patients with Hashimoto's thyroiditis, 30 with Graves' disease, five with papillary cancer, two with follicular adenoma, and two normal thyroid specimens. The expression of MHC class I and class II antigens was also evaluated. Most mononuclear infiltrates were LFA-1 positive, as expected. A positivity for ICAM-1 on follicular cells was observed in three out of four Hashimoto's thyroiditis specimens; such a phenomenon was totally absent in Graves' disease or any other pathological condition, or in normal tissue. MHC class II expression on thyrocytes was observed in all the patients with Hashimoto's thyroiditis, in 27 out of 30 with Graves' disease and in three out of five papillary cancer specimens.     

Heterogeneity of immunoregulatory T cells in human thyroid autoimmunity: influence of thyroid status.

Monoclonal antibodies of the OKT series were used to identify circulating T lymphocytes (OKT3+), their helper-inducer (OKT4+) and suppressor-cytotoxic (OKT8+) subsets and cells bearing Ia antigen (OKIa+) in 75 patients with thyroid autoimmune disorders, including 14 Graves' disease, 21 myxoedema, 20 asymptomatic thyroiditis, 12 Hashimoto's thyroiditis and eight simple goitre with superimposed thyroiditis. In the whole population of patients, a negative correlation was observed between the percentage of OKT8+ cells and serum free thyroxine levels whatever the type of thyroiditis. The percentage of OKT8+ cells was decreased in Graves' disease and increased in myxoedema while it reversed after adequate treatment of the two diseases. However, a trend to a decrease in the proportion of OKT8+ cells was still observed in treated Graves' disease and in all the other groups of thyroiditis with euthyroidism. The minor modifications observed for OKT3+ and OKT4+ cells were in relation with those of OKT8+ cells. There was an increased percentage of Ia+ cells in Graves' disease and in Hashimoto's thyroiditis partly reflecting the presence of activated lymphocytes. In conclusion, these data suggest first of all a direct influence of serum T4 on the distribution of circulating OKT8+ cells in addition to documenting the heterogeneity of T cell immunoregulatory factors.     

Tryptic peptides of human thyroglobulin: II. Immunoreactivity with sera from patients with thyroid diseases.

Tryptic peptides of human thyroglobulin (Tg) were analysed by Western immunoblot for their reactivity to circulating autoantibodies from patients with Hashimoto's thyroiditis (HT), Graves' disease (GD) and thyroid carcinoma, and from normal human controls. Low molecular weight peptides were released after 4 h incubation of Tg with trypsin. The sera of thyroid disease patients reacted with several peptides, but predominantly bound three peptides with apparent molecular weights (MWap) of 25 kD, 20 kD, and 15 kD; the sera of normal individuals did not bind these fragments of Tg. The pattern of tryptic peptides recognized by the majority of sera from GD patients differed from that recognized by sera from most patients with HT. Autoantibodies from both groups of patients recognized a 15-kD peptide with a high frequency, but the sera from 26/43 (60%) GD patients also recognized a peptide with MWap of 25 kD, whereas the sera from 22/35 (63%) of HT patients recognized a 20-kD peptide. A few sera from patients with thyroid carcinoma reacted with peptides with MWap of 15 and 20-kD, and none bound the 25-kD peptide. The immunoreactivity of autoantibodies in HT sera to the 20-kD peptide paralleled the competitive inhibition of the MoAb 137C1 by these sera. In addition, MoAb 137C1 and Hashimoto's sera showed the same Western immunoblot-binding pattern to Tg tryptic peptides, suggesting that a Hashimoto-associated epitope and the 137C1-binding site are found on the same peptide. These findings suggest that distinct peptides are recognized by Tg autoantibodies from patients with different thyroid diseases.     

Increase in peripheral natural killer cell activity in patients with autoimmune thyroid disease.

Changes in the activity and number of natural killer (NK) cells in peripheral blood in patients with autoimmune thyroid disease were examined. NK activity was measured in a 4-hr 51Cr-release assay and the number of NK cells was analyzed with FITC-conjugated monoclonal antibodies by use of an automated flow cytometer. NK activity in patients with untreated Graves' disease (n = 25, 39.7 +/- 13.5%, P less than 0.05) and Hashimoto's thyroiditis (n = 18, 41.0 +/- 14.2%, P less than 0.05) was high compared to the activity in non-pregnant controls (n = 61, 32.6 +/- 15.0%). NK activity in patients with postpartum Graves' thyrotoxicosis (n = 11, 48.6 +/- 18.9%) was markedly increased compared to the activity in non-pregnant controls (P less than 0.01) and in postpartum controls (n = 29, 33.8 +/- 15.2%, P less than 0.05), although the mean ages of each group did not differ significantly. Moreover, NK activities in the thyrotoxic state were significantly higher than those in the euthyroid state in the same patients with postpartum Graves' thyrotoxicosis or with postpartum destructive thyrotoxicosis. The number of CD16 positive cells increased in patients with postpartum Graves' thyrotoxicosis. However the number of CD16 and CD57 positive cells were normal in all other groups of patients. These results indicate that an increase of NK activity is associated with exacerbation of autoimmune thyroid disease both in Hashimoto's thyroiditis and in Graves' disease and suggest that NK cells might have an important role for the control of disease activity in autoimmune thyroid disease.     

Assays of TSH-receptor antibodies in 576 patients with various thyroid disorders: their incidence, significance and clinical usefulness

The incidence and the significance of TSH-receptor antibodies in Graves' disease and in various thyroid disorders have been evaluated. TSH-binding inhibiting antibodies (TBIAb) and thyroid stimulating antibodies (TSAb) were detected in a large proportion of Graves' disease patients (TBIAb in 68.8% and TSAb in 77.8%), in a small number of patients with idiopathic myxoedema or Hashimoto's thyroiditis, and were not detected in patients with endemic euthyroid goitre, differentiated thyroid carcinoma and toxic adenoma. Furthermore, TSH-receptor antibodies were present in some patients with toxic multinodular goitre (TBIAb in 12.7% and TSAb in 15.9%). When TSH-receptor and other thyroid autoantibodies were compared, it was found that 13 of the 15 Graves' patients with negative tests for thyroglobulin and thyroid microsomal antibodies were positive for TSH-receptor antibodies. On the other hand, 9 of the 11 patients with toxic multinodular goitre who had positive TSH-receptor antibody tests, also had serum thyroglobulin and/or thyroid microsomal antibodies. No significant differences in the prevalence of TSH-receptor antibodies were found in Graves' patients irrespective of the presence of ophthalmopathy or pretibial myxoedema. Elevated TBIAb activity at the end of anti-thyroid drug treatment was found in 52.9% of Graves' patients who subsequently relapsed, while in Graves' patients in remission TBIAb was always negative. TSH-receptor antibody results were not predictive of the outcome of radioiodine treatment in Graves' disease. Finally no correlation could be found between TBIAb and TSAb in Graves' disease and Hashimoto's thyroiditis. In conclusion: the high incidence of TSH-receptor antibodies in Graves' disease confirms their pathogenetic role in the development of hyperthyroidism; TSH-receptor antibodies in Graves' disease are not significantly associated with the presence of ophthalmopathy or pretibial myxoedema; TSH-receptor antibody assays may be useful for the diagnosis of Graves' disease in the absence of other signs of autoimmunity. TBIAb seems to be a good predictor of relapse in Graves' patients treated with anti-thyroid drugs; a fraction of toxic multinodular goitre could be a nodular variant of Graves' disease.     

Serum immunoglobulin levels in thyroid disease

Serum levels of IgG, IgA and IgM were assayed by radial immunodiffusion in 261 patients with eight categories of thyroid disease. These composed eighty-three patients with a first episode of untreated active Graves' disease (toxic diffuse goitre), ten with relapsed Graves' disease, seventeen with thyrotoxicosis due to a multinodular goitre, forty-nine with Hashimoto's thyroiditis, twenty-eight with primary (non-goitrous) myxoedema, forty with non-toxic goitre, eighteen with an adenoma and sixteen with euthyroid ophthalmopathy.

Eighteen (21·7%) patients with a first episode of Graves' disease had abnormally high IgG levels whereas eight (80%) of those who had relapsed after a course of Carbimazole had high levels. Those Graves' disease patients with raised IgG levels had a significantly higher 24-hr radioiodine uptake than those with normal levels. Eight (16·3%) patients with Hashimoto's thyroiditis had abnormally high levels of IgG associated with a higher incidence of thyroglobulin autoantibodies. Very few (<6%) patients with primary myxoedema, non-toxic goitre and adenoma had abnormal levels. Euthyroid patients with ophthalmopathy had a significantly lower mean IgG level than the corresponding mean level found in the group with active Graves' disease.

However, despite the differences between groups described above, there were no significant differences of mean IgG, IgA and IgM levels in seven of the eight groups when compared with normal subjects. Only the group with relapsed Graves' disease had a significantly higher mean IgG. None of the patients studied had abnormal IgM or IgA levels.

     

Circulating antibodies to DNA-related antigens in patients with autoimmune thyroid disorders.

A high prevalence of antibodies to double-stranded DNA (AbDNAds) has been recently reported in serum of patients with autoimmune thyroid disorders, but the specificity of this finding has been questioned. For this reason, the prevalence of several antibodies to DNA-related nuclear antigens (AbDRENA) has been evaluated in sera of patients with autoimmune and non-autoimmune thyroid disease. The study group included: 46 Graves' disease patients, 28 Hashimoto's thyroiditis patients, 25 patients with toxic nodular goitre and 11 with non-toxic nodular goitre. Twenty-eight Graves' patients were retested during methimazole (MMI) therapy, and 5 after radioiodine administration. Twenty-two patients with systemic lupus erythematosus and 28 normal subjects served as positive and negative controls, respectively. AbDRENA included: AbDNAds by RIA or immunofluorescence (IF); antibodies to single-stranded DNA (AbDNAss) and antibodies to histone (AbHist) by ELISA methods; antibodies to nuclear antigens (ANA) by immunofluorescence. RIA values were considered to be abnormal when 2 SD above the mean of normal controls. In our study 13% of Graves' patients were positive for AbDNAds by RIA: all of them had negative tests by IF; 11% were positive for AbDNAss, 2% for AbHist and 7% for ANA. A comparable prevalence of positive results for AbDNAds by RIA, with negative IF tests, was found in Hashimoto's thyroiditis patients. No significant changes of antibody levels were observed in Graves' patients during MMI treatment or after radioiodine administration. A positivity for AbDNAds or AbDNAss was found in 8% of patients with toxic nodular goitre, but in none of those with non-toxic goitre.(ABSTRACT TRUNCATED AT 250 WORDS)