It has been reported that receptor-bound blocking type TSH receptor antibody (TRAb) can be converted to the stimulating type by anti-human IgG antibodies. To evaluate the relationship between the conversion of receptor-bound blocking type TRAb to the stimulating type and the biological activity of blocking type TRAb, we compared converting activities of blocking type TRAb from 10 patients with primary nongoitrous hypothyroidism with both the doses of blocking type TRAb which show 50% inhibition of 125I-bTSH binding to the TSH receptor and those which show 50% inhibition of TSH-stimulated cAMP production in cultured rat thyroid cells (FRTL-5). The additions of anti-human IgG antibody to FRTL-5 cell-bound blocking IgGs resulted in the increase in cAMP production in a dose-dependent manner and the converting activities (percent increase of cAMP production) also depended on the doses of blocking IgGs. The converting activities were significantly correlated with the doses of blocking IgGs which showed 50% inhibition of 125I-bTSH binding to the TSH receptor (r = 0.71, p = 0.011). And these converting activities were also significantly correlated with the doses of blocking IgGs which showed 50% inhibition of TSH-stimulated cAMP increase (r = 0.81, p = 0.002), and were negatively correlated with thyroid stimulation blocking antibody activities (r = 0.58, p = 0.02). We have demonstrated that all cell-bound blocking type TRAb were converted to the stimulating type by anti-human IgG antibody and the degree of conversion was negatively correlated with the biological activity of blocking type TRAb.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult ; Aged ; Antibodies/*immunology ; Autoantibodies/*immunology ; Binding, Competitive ; Female ; Humans ; Immunoglobulin G/*immunology ; Immunoglobulins, Thyroid-Stimulating ; Middle Aged ; Receptors, Thyrotropin/*immunology ; Thyroid Gland/*immunology

Autoantibodies ; blood ; immunology ; Child ; Diagnosis, Differential ; Humans ; Radiography ; Radionuclide Imaging ; Thyroid Diseases ; blood ; diagnosis ; diagnostic imaging ; Thyroid Function Tests ; methods ; Thyroid Gland ; diagnostic imaging ; immunology ; Thyroid Hormones ; blood

OBJECTIVETo investigate the effect of cigarette smoking on thyroid gland volume, thyroid function and thyroid autoantibodies in the areas with different iodine intakes.

METHODSA cross-sectional epidemiological study in Panshan (mild iodine-deficient area), Zhangwu (more than adequate iodine intake area) and Huanghua (iodine-excessive area) was conducted in 3761 subjects in 1999.80.2 % of them were followed up in 2004. Questionnaires, thyroid function, thyroid autoantibodies, urinary iodine concentration,and thyroid B ultrasound were performed.

RESULTSThe prevalence of goiter was higher in smokers than in non-smokers (15.1% vs. 11.5%, P< 0.05). The average thyroid volume was higher in smokers with phenomenon more obvious in Panshan and Huanghua areas. Data from logistic analysis showed that smoking cigarette was an independent risk factor of goiter. There was no difference in serum TSH and Tg level between smokers and non-smokers. The positive rate of TPOAb (>100 IU/ml) was higher in smokers than in non-smokers(10.8% vs. 9.0 % , P <0.05) and was especially obvious in Huanghua area. Smoking was a independent risk factor of increasing positive rate of TPOAb. During the prospective observation,it was found that the incidence of positive TPOAb(>,100 IU/ml) was 7.4% in the subjects that were from non-smokers turning to smokers and 2.9% in those whose smoking behavior did not change. Logistic analysis indicated that the shifting from non-smoking to smoking was independent risk factor for the increase on high incidence of positive TPOAb.

CONCLUSIONSmoking cigarette was a independent risk factor of goiter. Smoking was also a risk factor of increasing TPOAb positive rate. Shifting from not smoking to smoking was an independent risk factor of increasing high incidence of positive TPOAb.

Autoantibodies ; blood ; Cross-Sectional Studies ; Female ; Goiter ; blood ; epidemiology ; immunology ; physiopathology ; Humans ; Incidence ; Male ; Smoking ; adverse effects ; Thyroid Function Tests ; Thyroid Gland ; physiopathology ; Thyroid Hormones ; blood

Subclinical hypothyroidism (SCH) is a common clinical condition, whereas it's natural course has not been identified distinctly. We evaluated the natural history of 169 SCH patients over 5-yr and the prognostic factors including thyroid autoantibodies and thyroid ultrasonographic (USG) findings related to develop overt hypothyroidism. After 5 yr, 47.3% of patients showed normalization of TSH, while 36.7% of patients remained persistence of high level of TSH, and overt hypothyroidism developed in 11.2% of patients. There were painless thyroiditis (2.9%) and hyperthyroidism (1.7%) during 5 yr follow-up. The thyroid nodule was seen in 48.6% of patients. Most of patients had 1 to 2 nodules whereas only 3% of patients with thyroid nodule had more than 6 nodules. Overt hypothyroidism patients had more heterogenous echogenecity in USG compared to patients with normalization or persistent SCH (76.5% vs 50.0% vs 35.0%, P = 0.048) and higher prevalence positive anti-thyroid peroxidase (anti-TPO Ab) and anti-thyroglobulin antibody (anti-Tg Ab) and titer of anti-TPO Ab than other two groups. The cut off values for prediction of overt hypothyroidism were TSH > 7.45 microIU/mL, free T4 < 1.09 ng/dL and Anti-TPO Ab > 560 IU/mL. SCH has various courses and initial TSH, free T4, presence of thyroid autoantibody, titer of thyroid autoantibody; and thyroid USG findings can serve as a prognostic factor for progression of overt hypothyroidism. These parameters suggest consideration to initiate thyroid hormone treatment in SCH.
Asymptomatic Diseases/*epidemiology ; Autoantibodies/blood/immunology ; Disease Progression ; Female ; Humans ; Hyperthyroidism/epidemiology ; Hypothyroidism/*epidemiology ; Male ; Middle Aged ; Prevalence ; Prospective Studies ; Republic of Korea/epidemiology ; Thyroglobulin/immunology ; Thyroid Function Tests ; Thyroid Gland/immunology ; Thyroid Nodule/epidemiology ; Thyroiditis/epidemiology ; Thyrotropin/*blood

We studied ninety cases of thyroid glands both histopathologically and by immunohistochemical methods in patients with Graves' disease using B and T cell markers to evaluate the role of lymphocytic subpopulation. Females were affected more frequently than males with a ratio of 6.5:1, and usually the females were younger than the males at the time of surgery. The heavier the lymphocytic infiltration, the higher was the percentage of germinal center formation or fibrosis. The degree of lymphocytic infiltration was also related to the titers of antithyroglobulin or antimicrosomal antibodies. T cells were mostly scattered individually or in small groups between the follicles; however, in the severely infiltrated group, the major pattern was in clusters. T8 positive cells were more abundant than T4 positive cells, and their distribution pattern was accordant with T11 positive cells. Immunoglobulin synthesizing B cells were positively stained in 47 of 94 cases tested and IgG was the most predominant. In the mild and moderate lymphocytic infiltration groups, IgM was mostly stained at the mantle zone or in the lymphoid cluster of the interfollicular stroma, whereas IgM positive cells were present exclusively in the germinal center of the severely infiltrated group. The results of our study indicate that the major lymphocyte subpopulation in Graves' disease is B lymphocytes, and the degree of T lymphocytic infiltration correlated better with titers of antimicrosomal antibody than antithyroglobulin.
Adolescent ; Adult ; Child ; Female ; Graves' Disease/immunology/*pathology ; Human ; Immunoglobulins/metabolism ; Lymphocytes/immunology/pathology ; Male ; Middle Age ; Support, Non-U.S. Gov't ; Thyroid Gland/immunology/pathology

OBJECTIVETo investigate the prevalence of positive thyroid antibodies in children with type 1 diabetes mellitus (T1DM) and its influencing factors.

METHODSThe clinical data of T1DM children who were treated in the Children's Hospital of Zhejiang University from May 2005 to April 2011 were retrospectively studied. The relationships of thyroid globulin antibody (TGAb) and thyroid peroxidase antibody (TPOAb) with cytokines IL-2, IL-4, IL-6, IL-10, TNF and IFN-γ were evaluated, and the percentages of CD3+, CD4+ and CD8+ T-lymphocytes in peripheral blood were examined.

RESULTSA total of 186 T1DM children with complete data of both TGAb and TPOAb were included in the study, among whom 143 with normal TGAb and TPOAb levels and 43 (23.1%) presented with positive thyroid antibody (including 21 cases with both positive TGAb and positive TPOAb). Eighteen cases (9.7%) were diagnosed as autoimmune polyglandular syndrome type 3 variant (APS3v). Significantly more patients in the positive thyroid antibody group had a family history of diabetes than in the negative thyroid antibody group (27.9% vs 14.7%; P<0.05). The average age of the positive thyroid antibody group was 10.1±3.2 years, which was significantly greater than that in the negative thyroid antibody group (8.1±4.0 years) (P<0.05). The IL-2 level (4.48 ±1.27 pg/mL vs 2.82 ±0.84 pg/mL, P<0.05) and the percentage of peripheral CD3+ T-lymphocyte[(61±11)% vs (66±11)%; P<0.05] were also different between the positive and negative thyroid antibody groups.

CONCLUSIONSGenetic background and abnormal function of T-lymphocytes (especially higher IL-2 level) may be involved in the elevated prevalence of positive thyroid antibody in T1DM children.

Adolescent ; Autoantibodies ; blood ; Child ; Cytokines ; blood ; Diabetes Mellitus, Type 1 ; immunology ; Female ; Humans ; Male ; Polyendocrinopathies, Autoimmune ; etiology ; T-Lymphocytes ; immunology ; Thyroid Gland ; immunology

OBJECTIVEAbnormal maternal thyroid function is associated with preterm birth. However, this association stays dubious in relevant individual studies for ethnic difference reasons and lack of direct supporting data. This study aimed to evaluate the relationship between preterm birth and thyroid dysfunction or autoimmunity based on ethnic differences.

METHODSRelevant studies were identified through searches of MEDLINE, Excerpta Medica, Wan Fang, China Biological Medicine disc, and China National Knowledge Infrastructure from inception to June 15, 2016. Original articles in which an incidence or prevalence of thyroid dysfunction or autoimmunity before second trimester of pregnancy could be extracted were included.

RESULTSThirty-two unique studies were included for the final meta-analysis. Patients involved were divided into two groups: Group 1 (G1) and Group 2 (G2) comprising of Asian and Caucasian populations, respectively. Positive thyroid antibodies were associated with the occurrence of preterm birth in both G1 [odds ratio (OR): 3.62, 95% confidence interval (CI): 2.83-4.65] and G2 (OR: 1.35, 95% CI: 1.17-1.56); hypothyroidism, only in G2 (OR: 1.20, CI: 1.09-1.33); and subclinical hypothyroidism or hypothyroxinemia, in neither group.

CONCLUSIONThyroid autoimmunity may be a more favorable factor leading to preterm birth among pregnant women of different ethnicities, compared with thyroid dysfunction.

Autoimmune Diseases ; ethnology ; immunology ; physiopathology ; Autoimmunity ; Female ; Humans ; Infant, Newborn ; Male ; Pregnancy ; Pregnancy Complications ; ethnology ; immunology ; physiopathology ; Premature Birth ; ethnology ; immunology ; physiopathology ; Thyroid Diseases ; ethnology ; immunology ; physiopathology ; Thyroid Gland ; physiopathology

OBJECTIVETo evaluate the clinical validity of anti-thyroperoxidase antibody (anti-TPOAb) and anti-thyroglobulin antibody (anti-TgAb).

METHODSerum levels of anti-TPOAb and anti-TgAb were assayed using chemiluminescence immunoassay in 434 subjects, including 51 patients with Hashimoto's thyroiditis, 58 with Graves' disease, 68 with nodular goiter, 56 with thyroid adenoma and carcinoma, 56 with subacute thyroiditis, 65 with euthyroid non-thyroid endocrine disease, 35 with euthyroid non-thyroid autoimmune diseases, and 45 euthyroid controls.

RESULTSThe highest level and most positive results of serum anti-TgAb and anti-TPOAb were observed in patients with Hashimoto's thyroiditis (median 373 and 6 974 U/ml, positive rate 84.3% and 86.3%), followed by patients with Graves' disease (median 84 and 1 369 U/ml, positive rate 44.8% and 72.4%). Serum anti-TgAb and anti-TPOAb were also more common in patients with subacute thyroiditis and other autoimmune diseases than in the controls.

CONCLUSIONThe assay of serum anti-TPOAb and anti-TgAb by chemiluminescence immunoassy are useful in the differential diagnosis of autoimmune thyroid disease.

Adenoma ; blood ; Adolescent ; Adult ; Aged ; Autoantibodies ; blood ; Female ; Graves Disease ; blood ; Hashimoto Disease ; blood ; Humans ; Iodide Peroxidase ; immunology ; Male ; Middle Aged ; Thyroglobulin ; immunology ; Thyroid Gland ; immunology ; Thyroid Neoplasms ; blood ; Thyroiditis, Subacute ; blood

OBJECTIVETo explore the role of natural killer T (NK T) cells in the pathogenesis of Graves' disease.

METHODSNK T cell deficient mice and wild BALB/c mice were immunized with cells expressing TSH receptor once every two weeks 6 times. Two weeks after the final immunization, the mice were killed and serum thyroxine levels, anti-TSH receptor antibodies and thyroid pathological changes were examined.

RESULTSThe mean levels of TT(4) and TRAb in the immunized NK T cell deficient group were slightly elevated but significantly different from those of the non-immunized control group, while comparable to those in the immunized wild group. There were no significant changes of the activity levels of TSAb or TSBAb in the immunized NK T cell deficient mice compared to those in immunized wild control mice. Thyroids from immunized NK T cell deficient mice showed mild hypertrophy of some follicles as compared with non-immunized control mice. This change was comparable to immunized wild control mice.

CONCLUSIONNK T cells may not be involved in the pathogenesis of Graves' disease.

Animals ; CHO Cells ; Cricetinae ; Female ; Graves Disease ; etiology ; immunology ; Immunization ; Killer Cells, Natural ; physiology ; Mice ; Mice, Inbred BALB C ; Receptors, Thyrotropin ; immunology ; Thyroid Gland ; pathology

OBJECTIVETo observe the effects of iodine on the level of CD4/CD8 cells and the production of thyroglobulin autoantibody (TGAb) and thyroid peroxidase autoantibody (TPOAb) in Wistar rats and to investigate the role of iodine in thyroid autoimmunity.

METHODSRat models with different iodine intakes including low iodine (LI,), normal iodine (NI,), 5 times normal iodine (5HI), 10 times normal iodine (10HI), 50 times normal iodine (50HI) and 100 times normal iodine (100HI) were established. The amount of iodine intake per rat per day in every group was about < 1, 6.15, 30.75, 61.50, 307.50, 615.00 microg separately. The levels of CD4 and CD8 immune cells in peripheral blood were measured by using flow cytometry. Radioimmunoassay (RIA) was used to determine the titers of TGAb and TPOAb in the serum.

RESULTSIn peripheral blood, the level of CD4 cells in LI group was (57.9 +/- 4.3)%, being much higher than in NI group (51.2 +/- 4.9)%. When the level of CD8 cells in 100HI group was (18.4 +/- 3.1)% showing significantly lower than in NI group (26.5 +/- 4.1)%, thus making the ratio of CD4/CD8 cells in the above two groups (LI: 2.4 +/- 0.40 and 100 HI: 2.7 +/- 0.4) higher than in NI group (1.9 +/- 0.3). As comparing with NI group (2099 +/- 220) CPM, the level of TGAb in LI group (1510 +/- 221) CPM was significantly decreased; while in 50HI group (3986 +/- 286) and 100HI group (3550 +/- 378) CPM, the levels of TGAb were both increased, and the levels of TPOAb in 10HI group (2066 +/- 184) CPM and in 50HI group (2141 +/- 163) CPM were both distinctly lower than in NI group (2372 +/- 245) CPM.

CONCLUSIONSIodine might exert influence on the level of CD4/CD8, and thus the production of thyroid antibodies might directly or indirectly take part in the process of thyroid autoimmunity. Both low iodine and 100 times normal iodine intakes might activate the immune state on some degrees. The effects of iodine on immune responses of TG and TPO antigen in thyroid autoimmunity might not be completely the same.

Animals ; Autoantibodies ; immunology ; Autoimmunity ; drug effects ; CD4-CD8 Ratio ; Drug Overdose ; Iodine ; adverse effects ; deficiency ; Rats ; Rats, Wistar ; Thyroid Gland ; drug effects ; immunology