The relative antigen-neutralizing capacity (avidity) of thyroglobulin antibodies in various thyroid diseases as measured by haemagglutination-inhibition with antibody-coated cells

Human sera which in a haemagglutination test with thyroglobulin-coated cells revealed thyroglobulin-antibody titres of 5⁵ or more were tested by a haemagglutination-inhibition technique with cells coated with highly purified rabbit antibody to human thyroglobulin. Theoretical considerations indicated that the titres obtained in this inhibition system would be influenced not only by the concentration of thyroglobulin-antibody, but also by the avidity of the antibody. Therefore, it should be possible to disclose differences in antibody avidity by comparing the inhibiting and agglutinating activity of the sera.

Based on these assumptions, sera from twenty-four patients with lymphadenoid goitre were found generally to contain highly avid thyroglobulin antibodies, although a decrease in avidity could apparently occur during the disease. Similar findings were made with sera from twenty-three patients with primary myxoedema, whereas sera from twelve thyrotoxic patients yielded relatively weaker inhibition reactions and were of a significantly lower avidity. Antibodies of very low avidity were found in five of seven cases with a clinical diagnosis of non-toxic goitre (or in all five cases of histologically verified non-toxic goitre), in two of three patients with cancer of the thyroid, and in two patients with subacute thyroiditis. These differences in reactivity of the thyroglobulin-antibodies may refer to different pathogenic mechanisms eliciting the autosensitization.

     

Antitissue antibodies in interstitial cystitis

Sera from thirty-three female patients with interstitial cystitis were studied for the presence of antitissue antibodies and a positive result was obtained in thirty-one cases (94%). Antinuclear antibodies detected by the immunofluorescence method were found in 85% of the sera in titres of 1:10 or higher. However, the LE-cell phenomenon was not seen in a single patient. complement-fixing antibodies to crude kidney homogenate occurred in 48% of the sera. Antibodies, with an incidence not exceeding that expected in control groups, were against smooth muscle, thyroglobulin and gastric parietal cells. None of the patients had mitochondrial or thyroid cytoplasmic antibodies, rheumatoid factors or biologic false-positive reactions for syphilis.

Bladder specific antibodies could not be demonstrated by the double layer immunofluorescence method.

The results indicate that interstitial cystitis belongs to that group of autoimmune diseases in which the disease is restricted to one organ, whereas the autoantibodies are non-organ specific.

     

Cell-mediated responses to heterologous and homologous thyroglobulin in guinea-pigs immunized with heterologous thyroid extracts

Immune cellular responses and circulating antibodies to heterologous and homologous thyroglobulin have been studied in two groups of guinea-pigs immunized with human or bovine thyroid extract in Freund's complete adjuvant. In animals immunized with human thyroid extract, the in vitro [2-¹⁴C]thymidine incorporation by lymphocytes and the inhibition of peritoneal exudate cell migration in the presence of human thyroglobulin were earlier and more marked than those to bovine thyroglobulin as observed in animals immunized with bovine thyroid extract. In the two groups of guinea-pigs no significant difference was found regarding the production of circulating antibodies.

Moreover cellular cross-reaction to homologous thyroglobulin could be detected in animals immunized with human but not in those immunized with bovine thyroid extract. Serological and cellular cross-reactions between human and bovine thyroglobulin were present in both groups of guinea-pigs.

Finally a significantly higher incidence of thyroid inflammatory lesions was found in the human thyroid extract immunized animals. The role of cell-mediated immune responses in initiating tissue damage in experimental thyroiditis is discussed.

     

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.     

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.     

Association of Sperm Antibodies With Other Autoantibodies in Infertile Men

PROBLEM: In many autoimmune diseases there is an increased incidence of other autoantibodies. However, the incidence of other autoantibodies in patients with seminal sperm antibodies is unknown. The most widely used tests to detect seminal and serum sperm antibodies are the mixed antiglobulin reaction (MAR) and the Tray agglutination test (TAT). METHOD: We therefore determined the incidence of antinuclear, antimitochondrial, thyroid peroxidase, and thyroglobulin antibodies, and rheumatoid factor in 147 patients investigated with MAR and 157 patients investigated with TAT. RESULTS: TAT positive patients had a significantly elevated incidence of antinuclear antibodies (χ² test, P < 0.005) and thyroglobulin antibodies (χ² test, P < 0.001). Thyroglobulin antibodies were increased in patients with MAR IgG > 40% and also significantly (χ² test, P < 0.05) increased in MAR IgA positive patients. Furthermore, thyroid peroxidase antibodies were only found in TAT positive patients. CONCLUSIONS: The consistently increased incidence of thyroid autoantibodies in infertile patients with sperm antibodies may indicate an increased risk for the development of autoimmune thyroid disease. This finding therefore suggests screening of patients with immunologic infertility for autoimmune thyroid disease and a further evaluation of the prognostic and pathophysiologic significance of thyroid autoantibodies in immunologic infertility.     

The release of thyroglobulin from the thyroid gland into thyroid lymphatics; the identification of thyroglobulin in the thyroid lymph and in the blood of monkeys by physical and immunological methods and its estimation by radioimmunoassay

The iodoprotein which was found in the lymph draining from the thyroid gland of monkeys has been identified as thyroglobulin, both by physical and by immunological techniques.

A sensitive and highly specific radioimmunoassay was developed by which thyroglobulin has been estimated in the thyroid lymph and in the blood of these animals.

Small but appreciable concentrations of thyroglobulin were found in thyroid venous and in peripheral blood. Non-thyroid lymph did not usually contain detectable concentrations of thyroglobulin but thyroglobulin was regularly found in thyroid lymph, sometimes in high concentrations. Thyroid stimulating hormone raised the concentration of thyroglobulin in the thyroid lymph still higher as did gentle massage of the tissues overlying the gland.

It was shown that the release of thyroglobulin into the thyroid lymph was a normal physiological process, for the possibility that it might have been released as a result of radiation or operative damage to the thyroid gland was excluded by experiments in which the need for administration of radioisotope to the animals was avoided and in which samples of lymph were obtained by cannulation of a cervical lymphatic trunk at some distance from the thyroid gland itself.

The implications of these findings are discussed in relation to the autoimmune phenomena seen in human thyroid disease.

     

Anti-thyroid peroxidase antibodies in thyroid disorders and non-thyroid autoimmune diseases.

A new commercial method for measurement of anti-thyroid peroxidase (anti-TPO DYNOtest, Henning, Berlin) was evaluated in normal subjects and in patients with autoimmune thyroid and non-thyroid diseases, and compared to an immune fluorescence method for measurement of anti-microsomal antibodies (MicAb), and a radioimmunological method for quantifying thyroglobulin antibodies (TgAb). The majority of normal subjects had anti-TPO levels below 52 U/ml and patients with Hashimoto's thyroiditis had levels above 200 U/ml, with a good correlation to MicAb. In other autoimmune thyroid diseases the correlation was less pronounced. In non-thyroid autoimmune diseases MicAb showed falsely positive reactions in the presence of other autoantibodies, e.g. mitochondrial antibodies. The present study indicates that the anti-TPO method should probably replace measurements of MicAb for routine clinical use, thus providing a sensitive, precise, antigen specific method with the ability to reveal quantitative fluctuations. The study also indicates that TgAb could be abolished in routine diagnosis of autoimmune thyroid diseases and be reserved for special clinical situations, research purposes as well as measurement in sera before evaluation of serum thyroglobulin levels.     

IgG subclass distribution of thyroglobulin antibodies in patients with thyroid disease

The IgG subclass distribution of thyroglobulin antibodies (TgAb) has been studied in Hashimoto and Graves’ patients by several investigators with conflicting results, in part explainable by methodological problems. We have recently developed a quantitative ELISA to measure in absolute terms the serum concentration of TgAb subclasses. The aim of the present study was to apply this method in a large series of patients with autoimmune as well as, for the first time, non-autoimmune thyroid diseases. We examined 28 patients with Hashimoto's thyroiditis, 30 with Graves’ disease, 21 with thyroid carcinoma and 18 with non-toxic goitre, all selected for the presence of TgAbs. The results indicated that TgAbs in thyroid diseases were not restricted to any particular isotype, but comprised all four IgG subclasses. IgG1 was represented similarly in the four groups. The same was true for IgG3, even though its contribution to the total antibody content was very small. IgG4 was the dominant subclass in patients with Graves’ disease, thyroid carcinoma and non-toxic goitre, probably reflecting a prolonged antigenic challenge. In Hashimoto's thyroiditis IgG2 was dominant, possibly because T helper lymphocytes infiltrating the thyroid are typically Th1 type.     

Serum autoantibodies and thyroid lymphocytic infiltration in endemic goitre.

Patients with thyroid diseases from areas of endemic goitre in Northern Italy were examined for thyroid antibodies by passive haemoagglutination. Of 40 schoolboys with goitre only one had thyroid antibodies (AT) in the blood. Among 182 adults with grade 1-2 goitre, examined within an area of low endemia, the frequency of AT was 7%, not significantly different from that found in the 286 persons with thyroid 'O' living in the same area. Among 181 adults with grade 2-3 goitre, examined within an area of serious endemia, the frequency of AT was 16%; the percentage went up to 24% in 144 patients operated on for goitre. AT frequency was 36% in 87 patients with toxic goitre, more than 70% in 97 patients with Graves' disease and 17% in 60 patients with cancer of the thyroid. AT occurred three times more frequently in women than in men. Microsomal antibodies were more frequently detected than anti-thyroglobulin antibodies: the opposite was true in thyroid cancer. Lymphocytic infiltration (IL) of the gland was observed in 45% of the 464 simple goitres and in 52% of the 60 cancers of the thyroid: it was more frequent and intense in women. Among the 144 patients operated on for goitre the frequency and the titre of AT progressed in parallel with the intensity of the lymphocytic infiltration. Patients with a greater lymphocytic infiltration and higher AT had a higher TSH. Multinodular non-toxic goitre and autoimmune lymphocytic thyroiditis can be present in the same thyroid gland and the clinical expression will depend on which condition predominates.     

Antibodies to salivary duct cells, and other autoantibodies, in patients with Sjögren''s syndrome and other idiopathic autoimmune diseases

Sera from thirty patients with Sjögren's syndrome were studied for the presence of antibodies to salivary duct cells. In sixteen cases (53%) a positive result was obtained.

The antibodies were present in the IgG globulins, in the IgM globulins also in nearly 50% of the IgG-positive cases, and rarely in the IgA globulins. One-third of the antibodies proved to be complement-fixing. No antibodies were found in normal controls matched for sex and age.

An antinuclear factor (ANF) was demonstrated in 77% of the sera. A rheumatoid factor was shown in 48% of the sera using a modified Waaler–Rose test and in 100% using a Latex fixation test. Antibodies to smooth muscle were present in 19%. Antibodies to skeletal muscle, gastric parietal cells, thyroid antigens, adrenocortex and mitochondria were found in frequencies which did not differ significantly from those in matched controls.

No correlation was demonstrated between antibodies to salivary duct cells and any of the other antibodies mentioned. Antibodies to salivary duct cells could only be absorbed with salivary gland tissue and not with other tissues. Antibodies to salivary duct cells were also found in patients with rheumatoid arthritis (22%), systemic lupus erythematosus (SLE) (18%) and myasthenia gravis (11%). They were extremely rare in patients with pernicious anaemia, autoimmune thyroiditis and idiopathic adrenocortical insufficiency. The antibodies could not be confirmed as being directed against the patient's own parotid tissue, probably due to loss of antigenic determinants as a result of the disease process. However, other findings support the opinion that Sjögren's syndrome is an idiopathic autoimmune disease.

     

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.     

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)     

Experimental thyroiditis in the rhesus monkey. IV. The role of thyroglobulin and cellular antigens

Nine normal rhesus monkeys were injected with homologous thyroid preparations, consisting either of a crude extract, partially purified thyroglobulin, or enzymatically dispersed viable cells. One monkey was injected with a preparation of heterologous human thyroid microsomes. The course of the disease was followed by periodic biopsies of the thyroid gland and by circulating antibodies. The latter were detected by tanned cell haemagglutination, complement fixation and cytotoxicity. The serum was also examined for levels of complement and for thyroid hormones.

Injection of partially purified monkey thyroglobulin resulted in the production of antibody both to thyroglobulin and to the cellular antigen. Inoculation of enzymatically dispersed viable thyroid cells led to a greater production of cytoplasmic antibody with a small and delayed production of antibody to thyroglobulin. Heterologous immunization of a monkey with human thyroid microsomes resulted in the production of autoantibodies to thyroid and minimal thyroid damage. There was considerable variation in antibody response and degree of tissue injury in different monkeys although injected with a similar antigen. There was no consistent association between circulating antibodies and pathological changes in the thyroid gland. Levels of complement varied but showed a definitive decrease in some animals with thyroiditis. There was no correspondence between tissue damage and protein bound iodine or thyroxine iodine.

     

Lymphocytic thyroiditis. II. The course of the disease in relation to morphologic, immunologic and clinical findings at the time of biopsy

Thirty-two patients with goitre and lymphocytic thyroiditis were followed for 1 1/2--19 years (average 7) after open surgical biopsy. Treatment with thyroid hormone was started when myxoedema was diagnosed. Five patients (group A) regained normal glandular size, remained euthyroid and had elevated antibody titres. Six patients (group B) continued to have goitre and elevated antibody titres and remained euthyroid. Thirteen patients (group C) developed myxoedema, while 8 (group D) demonstrated myxoedema at the time of biopsy. The patients in groups C and D had a higher average age and their biopsies showed more marked fibrosis compared with groups A and B. The goitre disappeared during treatment in 62% of the patients and the microsomal antibody titre also decreased in them, whereas the thyroglobulin antibody titre decreased in all treated patients. The results indicate that the degree of fibrosis in the thyroid gland is of overall importance for the prognosis with regard to glandular function. It seems evident that the treatment with thyroid hormone influences the autoimmune process so that the activity decreases.     

Circulating immune complexes in various thyroid diseases.

In a study of 171 patients with various thyroid diseases, circulating immune complexes (CIC), measured by a C1q solid phase radioassay, were detected in 26% of the patients as compared to 8% of the control subjects. CIC were found in 33--55% of the patients with a well defined thyroid autoimmune disorder (Hashimoto's goitre, asymptomatic thyroiditis, spontaneous myxoedema and Graves' disease) and also in the same proportion of patients with diffuse goitre. CIC were correlated to the presence of serum antibodies to microsomal thyroid antigen but not to their titre. No relationship was observed between CIC and the age or sex of the patients and the presence of exophthalmos, or between CIC and the different thyroid function tests or serum anti-thyroglobulin antibodies. CIC were found in untreated patients as well as in those treated with prednisone, methimazole or thyroxine.     

Studies on thyroid cell surface antigens using cultured human thyroid cells.

Human thyroid cells in primary culture were used for studies of thyroid cell surface antibodies in patients with thyroid autoimmune disorders. Radioiodinated IgG preparations containing thyroid microsomal antibody (TMAb), thyroid stimulating antibody (TSAb) and/or thyroglobulin antibody (TgAb) were tested for binding to thyroid cells. Binding was observed with radioiodinated IgG from patients with Graves' disease, Hashimoto's thyroiditis and idiopathic myxoedema containing TMAb, irrespective of the presence of TSAb and TgAb, while negative results were obtained with normal IgG. A dose-dependent inhibition of binding to thyroid cells was produced by the addition of the corresponding unlabelled IgG preparations. Evidence for tissue specificity was provided by the absence of binding to human skin fibroblasts used as controls. Preabsorption with human thyroid microsomes completely abolished the binding to thyroid cells of a radioiodinated TMAb positive IgG preparation, while only incomplete removal of the reactivity to thyroid microsomes was produced by preabsorption with thyroid cells. These data suggest that some but not all microsomal antigenic determinants are expressed on the thyroid cell surface. Binding to thyroid cells was also observed with purified TgAb, indicating that thyroglobulin antigenic determinants are present on the surface of thyroid cells. No evidence of binding was obtained with a TSAb positive Graves' IgG preparation with undetectable TMAb and TgAb. Unlabelled IgG preparations containing TMAb from patients with either Hashimoto's thyroiditis or idiopathic myxoedema were shown to inhibit the binding to thyroid cells of radioiodinated TMAb positive Graves' IgG and vice versa. These data indicate that antibodies present in these thyroid autoimmune disorders share common thyroid cell surface antigens. However, the binding of radioiodinated IgG from a patient with idiopathic myxoedema was only partially inhibited by Graves' or Hashimoto's IgG, suggesting that some of the thyroid cell surface antibodies of idiopathic myxoedema may not be detectable in other thyroid autoimmune disorders.     

An analysis of gastric parietal cell antibodies and thyroid cell antibodies in patients with pernicious anaemia and thyroid disorders

An analysis of immunoglobulins responsible for gastric parietal cell antibodies and for antibodies to thyroid cell has been performed in twenty-four patients with pernicious anaemia and thirteen patients with thyroid disorders. Immunofluorescent technique with conjugated antisera specific to each of the three main immunoglobulins and to β_1c-globulin was used.

IgG-globulin was responsible for gastric parietal cell antibodies in all patients investigated; IgA was found in gastric parietal cell antibodies of four thyroid patients but in none of the pernicious anaemia patients; IgM antibodies were found in two pernicious anaemia patients and in six thyroid patients. With regard to thyroid cell antibodies, IgG and IgA were both found responsible for antibody activity in thirteen cases and IgM in ten cases. In six patients, antibodies to thyroid cell were not β_1c-fixing, whereas all sera with gastric parietal cell antibodies fixed β_1c-globulin.

An obvious relationship could not be found either between the titres of the different types of antibodies within the same category of antibody, or between the titres of gastric parietal cell antibodies and thyroid cell antibodies in the same individual. An occasional relationship was found between the titres of IgG-parietal cell or thyroid cell antibodies and the capacity to bind β_1c-globulin.

These results demonstrate that each of the three main immunoglobulins may contribute to gastric parietal cell antibodies and to antibodies to thyroid cell.

     

Autoantibodies against complement C1q correlate with the thyroid function in patients with autoimmune thyroid disease

Autoantibodies against complement C1q (anti-C1q) have been well described in patients with systemic lupus erythematosus, where they correlate with the occurrence of severe lupus nephritis. However, data on anti-C1q in organ-specific autoimmune diseases are scarce. In order to determine the prevalence of anti-C1q in patients with autoimmune thyroid disorders (AITD) and a possible association with thyroid function, we measured prospectively anti-C1q in 23 patients with Graves' disease (GD) and 52 patients with Hashimoto's thyroiditis (HT). Anti-C1q levels were correlated with parameters of thyroid function and autoantibodies against thyroperoxidase, thyroglobulin and thyroid stimulating hormone (TSH) receptor. Twenty-one patients with multi-nodular goitre and 72 normal blood donors served as controls. We found elevated concentrations of anti-C1q more frequently in patients with AITD than in controls: seven of 23 (30%) patients with GD and 11 of 52 (21%) patients with HT, compared with one of 21 (5%) patients with multi-nodular goitre and six of 72 (8%) normal controls. Anti-C1q levels did not correlate with thyroid autoantibodies. However, in GD absolute levels of anti-C1q correlated negatively with TSH and positively with free thyroxine (FT4) and triiodothyronine (FT3). In contrast, in HT, anti-C1q correlated positively with TSH levels. No correlation between TSH and thyroid autoantibodies was found. In conclusion, we found an increased prevalence of anti-C1q in patients with AITD and their levels correlated with the thyroid function in both GD and HT. This correlation seems to be independent of thyroid autoantibodies. Therefore, anti-C1q might point to a pathogenic mechanism involved in the development of AITD that is independent of classical thyroid autoantibodies.     

The effect of thyroid antigens on the in vitro migration of leucocytes from patients with Hashimoto thyroiditis

A total of fifty-two patients with Hashimoto thyroiditis were tested for delayed hypersensitivity to thyroid antigens using the leucocyte migration test. The percentage of patients showing abnormal migration in the presence of crude thyroid extract, thyroglobulin, thyroid mitochondria and thyroid microsomes was 75, 44, 54 and 34% respectively. Fifty-three control patients were studied concurrently with the same antigens and the percentage showing abnormal migration was 4, 6, 6 and 6% respectively. The antigenic activity of the mitochondrial fraction was not organ specific; both liver and kidney mitochondria interfered with the migration of leucocytes from patients with Hashimoto thyroiditis.