Prevention of experimental autoimmune thyroiditis through the anti-idiotypic network.

The central goal in the therapy of autoimmune diseases is to develop potent tools able to exert specific control of the immune response to self Ag. Anti-Id may provide such specific immunodulators because the relevance of the idiotypic network in autoimmunity is well documented. We now describe the protective immunity against experimental autoimmune thyroiditis induced exclusively by a thyroglobulin (Tg)-specific cytotoxic T cell clone and show that this down-regulation occurs through the generation of anti-Id antibodies (Ab) (Ab2Beta) which recognize the paratope of a anti-Tg mAb (Ab1) specific to the pathogenic epitope of the Tg molecule. We further analyze the various steps of the Ab responses (Ab1, Ab2, and Ab3) in terms of poly-, mono-, and autospecificities for the pathogenic epitope of the Tg molecule and for the idiotope of the related Ab.     

Th1 cytokines in autoimmune thyroiditis

This study was performed on a lot of 51 patients and intends to correlate the autoimmune thyroiditis to the synthesis of Th1 cytokines and to the activation of T lymphocytes. We find out that CD25, an activation marker of T lymphocytes, is significantly increased in these patients. We also find out that certain cytokine serum levels are increased (IL-2, TNF-alpha, IFN-gamma). These cytokines correspond to the secretor profile of the Th1 subset. Mononuclear cell culture supernatants showed an increased level of IL-2 and TNF-alpha in samples stimulated with ConA in comparison to unstimulated samples from the same patient, suggesting the existence of an expansioned Th1 and CD8+ cytotoxic population.     

Atrophic, autoimmune thyroiditis in infancy. A case report

Autoimmune thyroiditis in infancy is a very rare condition. Only 1 case has been reported previously. In the present patient an acquired primary hypothyroidism with high titers of thyroid microsomal antibodies was diagnosed at the age of 7 months. The patient died at 9 months of age in a sepsis-like condition. Autopsy revealed an atrophic thyroiditis. The more severe and complex clinical picture of autoimmune thyroiditis in infancy compared to that later in childhood is discussed.     

Selenium in the treatment of autoimmune thyroiditis

We recently conducted a prospective, placebo-controlled clinical study, where we could demonstrate, that a substitution of 200 microg sodium selenite for three months in patients with autoimmune thyroiditis reduced thyroid peroxidase antibody (TPO-Ab) concentrations significantly. Forty-seven patients from the initially 70 patients agreed to participate in a follow-up cross-over study for further six months. One group (n = 13), which initially received selenium continued to take 200 microg sodium selenite (Se-Se), one group stopped taking selenium (Se-0) ( n = 9), another group which received placebo started to take 200 microg selenium (n = 14) (Plac-Se) and the last group was without selenium substitution (Plac-0) (n = 11). TPO-Ab concentrations were measured at beginning and the end of the study. In the Se-Se group, the TPO-Ab concentrations further significantly p = 0.004) decreased from 625 +/- 470 U/ml to 354 +/- 321 U/ml, in the Se-0 group the TPO-Ab concentrations increased significantly p = 0.017) from 450 +/- 335 to 708 +/- 313 U/ml. In the placebo group, the TPO-Ab concentrations in those patients who were followed without selenium substitution were unchanged (1351 +/- 940 vs. 1724 +/- 1112 U/ml, p = 0.555). In contrast, the patients who received 200 microg sodium selenite after placebo, the TPO-Ab concentrations decreased significantly (p = 0.029) from 1182 +/- 723 to 643 +/- 477 U/ml.     

Effect in neonatal thymectomy on experimental autoimmune thyroiditis in guinea pigs.

These studies examined the effect of neonatal thymectomy on the induction of experimental autoimmune thyroiditis (EAT) in the guinea pigs. Thymectomy was found to result in a consistent and profound inhibition of the development of lesions of EAT in both strain 2 and strain 13 guinea pigs. Thymectomized guinea pigs also had reduced antibody titers to guinea pig thyroglobulin (GPTG), while delayed hypersensitivity reactions to GPTG were less markedly affected by thymectomy. Thymectomized guinea pigs had significant functional peripheral T cells as evidenced by normal responses of lymph node cells to T cell mitogens. These results indicate that a T cell subpopulation which is sensitive to neonatal thymectomy is required for the development of EAT and antithyroglobulin antibody in the guinea pig.     

Transfer of experimental autoimmune thyroiditis with T cell clones

We have investigated three T lymphocyte clones isolated from CBA/CaJ mice primed with mouse thyroid extract (MTE) in adjuvant. All three clones are L3T4+, Ig-, and Lyt2- and proliferate to MTE, mouse thyroglobulin (MTG) and rat thyroid extract. Clones A7 and B7 transfer thyroiditis to irradiated (475 rad) syngeneic mice, but not to normal recipients. The thyroid lesion induced by the B7 clone is characterized by the infiltration of both mononuclear and polymorphonuclear cells. The thyroiditis is transient in that lesions are apparent 7 and 14 days after transfer, but thyroids return to normal by day 21. Clone B7 showed helper activity for trinitrophenyl-keyhole limpet hemocyanin-primed B cells in vitro when stimulated with trinitrophenyl-MTG and also stimulated the production of anti-MTG antibody in recipient mice. Clone A7 induced thyroid lesions characterized by infiltration of the thyroid with mononuclear cells, with virtually no polymorphonuclear cell infiltration. This clone has shown no helper activity following stimulation with trinitrophenyl-MTG. The third clone (D2) proliferates to and shows helper activity to MTG, but fails to transfer thyroiditis to syngeneic, irradiated mice. On continuous culture, clone B7 lost its surface Thy. The loss of Thy appears unrelated to the ability to transfer thyroiditis since subclones of B7 with markedly different percentages of Thy+ cells transferred disease equally well.     

DNA content of Hurthle cell nodules in autoimmune thyroiditis

Hurthle cells are found in thyroid neoplasms and in reactive nodules in thyroiditis or goitrogenic processes. Cytometric studies have evaluated Hurthle cell neoplasms but not their reactive counterparts. DNA content of Hurthle cells in 22 cases of autoimmune thyroiditis was measured by flow cytometry and image content of Hurthle cells in 22 cases of autoimmune thyroiditis was measured by flow cytometry and image processing using nuclei extracted from paraffin-embedded tissue after microdissection of the Hurthle cell nodules. All 22 autoimmune thyroiditis Hurthle cell nodules were diploid, including 16 without associated neoplasms and six with associated malignant neoplasms (four papillary carcinomas, one follicular carcinoma and one follicular adenoma with papillary carcinoma). Concordance between flow cytometry and image processing was 100%. These findings indicate that the markedly atypical Hurthle cells in autoimmune thyroiditis are diploid by DNA quantitation. This suggests that atypia in Hurthle cells due to reactive or neoplastic processes may be differentiated by quantitative DNA analysis.     

Natural history of

Negative effects of human presence and activities on breeding success and survival of many water bird species are well documented. The New Zealand dabchick (Poliocephalus rufopectus) is a protected endemic New Zealand grebe, confined to the North Island mainland and classified as vulnerable. A third of the total New Zealand dabchick population live on the lakes of the central volcanic plateau, where there is potential conflict between humans and dabchicks. We used data from two independent surveys describing the distribution of New Zealand dabchicks to investigate the effect that human-made structures (i.e. jetties and houses) and human recreational activities (i.e. boating) have on the numbers of New Zealand dabchick pairs, chicks and nests in the bays of Lake Rotoiti, Tarawera and Okareka. Our results suggest that human-made structures and recreational activities are not significantly affecting the numbers and distribution of New Zealand dabchick pairs or nests at this time. Furthermore, the number of human-made structures was positively correlated with the number of chicks in the sampled bays. Humans and dabchicks may be distributed similarly around the lakes because factors such as wind exposure and shoreline topography made certain sites preferable for both species. Alternatively, humanmade structures may provide protected nesting environments and/or cover for chicks from predators, refuges from harassment by other bird species, or other benefits. Pairs may therefore be able to raise chicks to the fledging stage more successfully. However, little is currently known about dabchick life history or population dynamics. We recommend that a method of capturing and marking be developed so that further monitoring of behavioural and population changes can be carried out. It is also necessary to conduct research on how boats and human activities at jetties affect incubating dabchicks and their young during the nesting phase.     

Elevated prolactin to cortisol ratio and polyclonal autoimmune activation in Hashimoto's thyroiditis.

Cortisol and prolactin, which are considered to have an immunomodulatory effect, and selected autoantibodies were determined in Hashimoto's thyroiditis. 37 patients (8 males and 29 females) (54 +/- 13.8 years) and an equal number of sex- and age-matched normal subjects (52.6 +/- 14.2 years) were studied. None of the 74 subjects suffered from any other immunological, infectious, hepatic, renal or malignant diseases. Patients with Hashimoto's thyroiditis exhibited significantly higher (p < 0.016) prolactin values (14.0 +/- 3.8 ng/ml) than did control subjects (6.5 +/- 1.3 ng/ml). In contrast, cortisol levels were lower in Hashimoto's thyroiditis (13.5 +/- 3.2 microg/dl) vs. normal state (16.0 +/- 1.13 microg/dl), (p < 0.05). The prevalence of anti-TPO and anti-Tg antibodies was 100 % and 43 % in the patients with Hashimoto's disease. In contrast, no subject of the control group was positive for anti-TPO, although 9 subjects (24 %) were positive for anti-Tg autoantibodies. The percentage of positive autoantibodies to nucleus, smooth-muscle, and parietal cells in the patients (36.0, 10.9 and 18.5 %, respectively) was higher than that in healthy group (11.0 and 0 % respectively). Notably, neither group was positive for antibodies against double-stranded DNA or mitochondria. In conclusion, our results provide evidence for a polyclonal activity in Hashimoto's thyroiditis, an organ-specific autoimmune disease, associated with an altered prolactin-adrenocortical status. Such information should initiate longitudinal studies to clarify the exact time sequence of these events related to the disease's activity.