1.Progress of pathogenesis and clinical treatment of Hashimoto's thyroiditis.
Qing GAO ; Li-Xin JIAN ; Jin-Guo XU ; Wen-Lin LI ; Zhi-Wei JIAN ; Su-Hua PAN
China Journal of Chinese Materia Medica 2012;37(20):3003-3006
Hashimoto's thyroiditis (HT) is a autoimmune disease that is highly incident year by year. Its clinical manifestations are alternative hyperthyroidism or hypothyroidism, relatively high Th1, excessively low Th2 and constantly increasing TGAb and TMAB. Currently, the disease is still difficult to be cured, and instable thyroid function makes it harder to be treated. Therefore, this essay makes a summary analysis on domestic and foreign studies on HT's pathogenesis, clinical manifestations and treatment, resulting that pure supplement or immunosuppressive therapy is hard to achieve notable efficacy, while existing traditional Chinese medicines could only mitigate clinical symposiums but did not reduce inflammation. Therefore, to look for methods and drugs for adjusting immunity imbalance by decreasing Th1 cell factors and increasing Th2 cell factors is significant to HT treatment to some extent.
Animals
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Autoantibodies
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immunology
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Female
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Humans
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T-Lymphocytes, Helper-Inducer
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immunology
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Thyroiditis, Autoimmune
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drug therapy
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immunology
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pathology
2.Immunological Study on Autoimmune Postpartum Thyroiditis.
Hyeon Man KIM ; Kap Bum HUH ; Hyun Chul LEE ; Sung Kil LIM ; Kiil PARK ; Jung Koo YOUN ; Sang Yong LEE
Yonsei Medical Journal 1986;27(4):276-282
Autoimmune postpartum thyroiditis (PPT) has been thought of as one of the organ-specific autoimmune diseases. The present study was designed to investigate whether the immunological changes during the postpartum period might induce this disease, by comparing the circulating lymphocyte subsets and antibody-dependent cell-mediated cytotoxicity (ADCC) between normal postpartum women and PPT patients. The results were as follows: 1) No significant differences in the circulating total T lymphocyte population, or suppressor T lymphocyte subsets, or in Th/Ts ratio were found among 25 PPT patients, 11 normal postpartum women and 11 normal non-pregnant women. 2) In PPT patients, helper T lymphocyte subsets were fewer in proportion than those of normal postpartum or non-pregnant women. However, B lymphocyte population (19.7 +/- 7.8%) and ADCC activity (.41 +/- 13) in PPT patients were comparable to those in normal postpartum women (18.3 +/- 4.8%, .42 +/- .11), although they were significantly greater than those in normal normal non-pregnant women (13.3 +/- 5.9%, .29 +/- .07). In conclusion, the enhancement of immune activities observed in PPT patients was comparable to that in normal postpartum women, suggesting that some other causative or triggering factors might be responsible for the occurrence of this disease.
Adult
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Antibody-Dependent Cell Cytotoxicity
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B-Lymphocytes/immunology
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Female
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Human
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Pregnancy
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Puerperal Disorders/immunology*
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T-Lymphocytes/immunology
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Thyroiditis, Autoimmune/immunology*
3.The tumor necrosis factor beta * 1 allele is linked significantly to HLA-DR8 in Koreans with atrophic autoimmune thyroiditis who are positive for thyrotropin receptor blocking antibody.
Jae Hoon CHUNG ; Bo Youn CHO ; Hong Kyu LEE ; Tai Gyu KIM ; Hoon HAN ; Chang Soon KOH
Journal of Korean Medical Science 1994;9(2):155-161
The localization and functional characteristics of tumor necrosis factor(TNF) beta gene raise the possibility that it may be involved in the susceptibility to autoimmune thyroid diseases. To investigate whether a TNF beta gene polymorphism is associated with autoimmune thyroiditis, we analyzed the TNF beta gene polymorphism with the restriction enzyme NcoI in 48 Korean patients with atrophic autoimmune thyroiditis [23 were found to be thyrotropin binding inhibitor immunoglobulin(TBII) positive, 25 TBII negative], 52 goitrous autoimmune thyroiditis, and 129 healthy controls. Two TNF beta alleles were identified from the restriction fragment length polymorphism studies of amplified genomic DNA. In atrophic autoimmune thyroiditis patients positive for TBII, 7 of 23 patients were homozygous for the TNF beta * 1 allele, 3 were homozygous for the TNF beta * 2 allele, and 13 were TNF beta * 1/2 heterozygous compared to controls(P = 0.20). Also, there were no associations between the TNF beta gene polymorphism and either TBII-negative atrophic autoimmune thyroiditis or goitrous autoimmune thyroiditis. Of the HLA-class II antigens, the frequency of HLA-DR8 was significantly greater among the 23 Korean patients with TBII-positive atrophic autoimmune thyroiditis compared to control subjects (Pc = 0.003). When the HLA-DR8 positive patients with TBII-positive atrophic autoimmune thyroiditis and controls were analyzed separately, the DR8 positive patients with TBII-positive atrophic autoimmune thyroiditis had more homozygotes for the TNF beta * 1 allele(6/12, 50.0%) and no homozygotes for the TNF beta * 2 allele, as compared to the DR8 negative patients with TBII-positive atrophic autoimmune thyroiditis and DR8 positive controls(P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Alleles
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*Genetic Linkage
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HLA-DR Antigens/*genetics
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Humans
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Korea
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Lymphotoxin-alpha/*genetics
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*Polymorphism, Genetic
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Receptors, Thyrotropin/*immunology
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Thyroiditis, Autoimmune/*genetics
4.Immune intervention effects on the induction of experimental autoimmune thyroiditis.
Weihong CHEN ; Hanhua LIN ; Muti WANG
Journal of Huazhong University of Science and Technology (Medical Sciences) 2002;22(4):343-354
To explore immune intervention effects of the combined use of cycloporin A (CsA) and 1, 25-dihydroxyvitamin D3[1,25(OH)2D3] at low doses on experimental autoimmune thyroiditis (EAT), porcine thyroglobulin (pTG) was injected into a CBA mouse at the dose of 100 micrograms on day 0 and day 14 to establish the model of EAT. The immune prevention group from day 0 to day 28, and treatment group from day 10 to day 38 were daily administered CsA (10 mg/kg) intragastrically and/or 1,25(OH)2D3 (0.2 microgram/kg) i.p. After immunized by pTG, the mice were sacrificed on day 28 and day 38 to examine their thyroid gland pathologically, and to check the levels of serum porcine thyroglobulin antibodies (pTGAb), porcine thyromicrosomal antibodies (pTMAb). The incidences of EAT in the immune prevention group and treatment group, with administration of low dose of CsA and 1,25(OH)2D3, were decreased respectively by 44.44% and 37.50%. Those of severe disease in the two groups were decreased respectively by 71.43% and 60.32%. The levels of serum pTGAb and pTMAb in the immune prevention group were lower than those of the positive control group. It was concluded that combined use of CsA and 1,25(OH)2D3 at low doses could effectively prevent EAT with a synergic effect.
Animals
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Antibodies
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blood
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Calcitriol
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therapeutic use
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Cyclosporine
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therapeutic use
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Drug Synergism
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Female
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Mice
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Mice, Inbred CBA
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Thyroglobulin
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immunology
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Thyroiditis, Autoimmune
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drug therapy
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immunology
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prevention & control
5.Multifactorial analysis of effects of mothers' autoimmune thyroid disease on their infants' intellectual development.
Hong ZHU ; Zheng-yan ZHAO ; You-jun JIANG ; Li LIANG ; Ji-yue WANG ; Hua-qing MAO ; Chao-chun ZOU ; Li-qin CHEN ; Yi-ping QU
Chinese Journal of Pediatrics 2005;43(5):340-344
OBJECTIVETo analyze factors relevant to retarded intellectual development in infants born to mothers with autoimmune disease of thyroid.
METHODSAll the term newborns born to mothers with autoimmune thyroid disease (selection criteria) without asphyxia in all county, city, and provincial hospitals in Zhejiang province (except for Ningbo City) from July 2001 to June 2003 were enrolled through Zhejiang provincial neonatal disease screening network system. The control group was consisted of the neonates who were born to mothers without thyroid disease in these hospitals during the same period. Heel capillary blood samples were collected from the neonates older than 3 days in local hospitals and sent to the center of Zhejiang provincial neonatal disease screening network system. TSH levels were measured by Time Difference Fluorescent Analysis Device (1420 II type, EGG Company, US). If the level of TSH was higher than 9 mU/L, their mothers were called back to the center with their infants within 3 days. If the level of TSH was normal, they were called back to hospitals at age of 28 - 35 days of infants. The pattern of maternal thyroid disease, duration, thyroid function, the history of maternal drug administration, maternal age, gestational age and body weight of the neonates were recorded. The neonatal and maternal serum thyroid function tests were re-performed and the serum TPOAb, TGAb, TRAb and TSAb levels in both neonates and their mothers were measured as well. A 1-year follow-up study was done and all these subjects were investigated by means of Gesell development schedules by special investigators at the age of 1, 3, 6 and 12 months. The results were expressed as developmental quotient. Case-sectional study was performed. Statistical analyses were conducted using SPSS software. The multiple logistic regression analysis was used to analyze factors which might have effect on infantile personal-social ability, adaptive ability, gross motor ability or the fine-motor ability. One-way ANOVA was used to compare those five subfields ability followed by LSD multiple comparisons and Dunnet's C test was used when variances were not equal. Correlation analysis was used to compare the anti-thyroid antibody between neonates and their mothers.
RESULTSPoor personal-social ability, adaptive ability, gross motor ability and fine motor ability of infants born to mothers with autoimmune thyroid diseases were found as compared to the infants born to healthy mothers (P < 0.01). Moreover, the infants born to mothers with Hashimoto's thyroiditis had significantly poorer fine motor ability and adaptive ability than those born to mothers with Grave's disease (P < 0.05). The Spearman correlation coefficients of TPOAb, TGAb, TRAb and TSAb were 0.636, 0.574, 0.619 and 0.473, respectively, and all the P values were lower than 0.01.The multifactor logistic regression analysis showed that infantile TPOAb levels and maternal TRAb levels were associated with infantile personal-social ability, adaptive ability, and gross motor; while maternal TPOAb levels and thyroid function during gestation were associated with infantile fine-motor ability (P < 0.05).
CONCLUSIONMaternal autoimmune thyroid diseases during pregnancy had adverse effects on intellectual development of infants. The maternal levels of TPOAb, TRAb and thyroid status were associated with the infantile personal-social ability, adaptive ability, gross motor and fine motor development. In order to reduce the effect on infant, it is necessary to treat adequately the maternal autoimmune thyroid diseases during pregnancy.
Adult ; Autoantibodies ; blood ; Female ; Humans ; Infant, Newborn ; Intellectual Disability ; etiology ; Intelligence ; Iodide Peroxidase ; immunology ; Pregnancy ; Pregnancy Complications ; Risk Factors ; Thyroiditis, Autoimmune ; complications
6.Autoantibodies against thyroid hormones and their influence on thyroxine determination with chemiluminescence immunoassay in dogs.
Marion PIECHOTTA ; Michael ARNDT ; Hans Otto HOPPEN
Journal of Veterinary Science 2010;11(3):191-196
Autoantibodies against thyroxin (T4AA) and triiodothyronine (T3AA) are present in dogs with autoimmune thyroiditis and have been reported to interfere with immunoassays. The objectives of this study were to determine the frequency of autoantibodies and to determine whether interference occurs by T4AA, using a non-immunological method (high performance liquid chromatography, HPLC) for thyroxin (T4) measurement. Based on clinical symptoms, T4 and thyroid stimulating hormone (TSH) concentration, 1,339 dogs were divided into six groups: Group 1: hypothyroid (n = 149); Group 2: subclinical thyroiditis (n = 110); Group 3: suspicious for non thyroidal illness (n = 691); Group 4: biochemical euthyroid (n = 138); Group 5: hypothyroid dogs under substitution therapy (n = 141); Group 6: healthy dogs (n = 110). The incidence of T4AA and T3AA, determined using radiometric assay, was low (0.5% and 3.8%) and higher in hypothyroid dogs compared to dogs suspicious for hypothyroidism (Group 2-4) (p<0.05). T4AA was not detected in dogs with normal T4 and elevated TSH. T4 concentrations of T4AA positive samples determined using HPLC were comparable to results obtained by chemiluminescence immunoassay. These findings indicate that the probability of interference of T4AA leading to falsely elevated T4 concentration in the T4 assay seems to be low.
Animals
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Autoantibodies/*immunology
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Chemiluminescent Measurements/methods/*veterinary
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Chromatography, High Pressure Liquid/veterinary
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Dog Diseases/*diagnosis/*immunology
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Dogs
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Immunoassay/methods/*veterinary
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Thyroid Hormones/*immunology
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Thyroiditis, Autoimmune/diagnosis/immunology/*veterinary
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Thyroxine/*blood
7.Selenium supplementation alleviates autoimmune thyroiditis by regulating expression of TH1/TH2 cytokines.
Long TAN ; Zhong Na SANG ; Jun SHEN ; Yun Tang WU ; Zhai Xiao YAO ; Jin Xiang ZHANG ; Na ZHAO ; Wan Qi ZHANG
Biomedical and Environmental Sciences 2013;26(11):920-925
Animals
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Autoantibodies
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blood
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Cytokines
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biosynthesis
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Dose-Response Relationship, Drug
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Female
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Immunohistochemistry
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Rats
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Rats, Inbred Lew
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Selenium
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administration & dosage
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therapeutic use
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Th1 Cells
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drug effects
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immunology
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Th2 Cells
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drug effects
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immunology
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Thyroid Gland
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drug effects
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immunology
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pathology
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Thyroiditis, Autoimmune
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drug therapy
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immunology
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Trace Elements
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administration & dosage
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therapeutic use
8.Xiaoyin recipe ( ) for psoriasis induces a Th1/Th2 balance drift toward Th2 in peripheral blood mononuclear cells of experimental autoimmune thyroiditis rats.
Xiao-Guang XU ; Hong ZHANG ; Xin-Ling BI ; Jun GU ; Yu-Ling SHI ; Qiang HOU
Chinese journal of integrative medicine 2012;18(2):137-145
OBJECTIVETo explore the regulatory mechanism of Xiaoyin Recipe () on the T helper 1/T helper 2 (Th1/Th2) immune balance.
METHODSThirty-six experimental animals were divided into three groups, 12 rats in each group: blank control group (B group), negative control group (N group), and Xiaoyin Recipe treatment group (T group). The latter two groups received immunization of experimental autoimmune thyroiditis (EAT), and T group were treated with Xiaoyin Recipe for a month. Then, the expression of Th1-Th2-related genes in peripheral blood mononuclear cells (PBMCs) were screened with Oligo GEArray Rat Th1-Th2-Th3 Microarray. The expressions of tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), T-box expressed in T-cells (T-bet), and GATA-binding protein-3 (GATA-3) were detected by real-time polymerase chain reaction (RT-PCR).
RESULTSGene array screening showed that compared to N group, in T group after Xiaoyin Recipe treatment, 3 genes were upregulated in EAT rats, including interleukin-27 receptor alpha (IL-27rα), glomulin (Glmn), and GATA-3, while 38 genes were downregulated, such as CD28, IL-18, signal transducer, and activator of transcription 1 (STAT1), T-bet, TNF receptor superfamily member 4 (TNFRSF4), TNF ligand superfamily member 5 (TNFSF5), and TNF receptor superfamily member 5 (TNFRSF5). While RT-PCR showed that there was an increased level of TNF-α mRNA (P<0.01), an elevated ratio of T-bet/GATA-3, and a decreased level of IL-10 mRNA in PBMC of N and T group compared to B group (P <0.01); and after treatment with Xiaoyin Recipe, IL-10 mRNA level increased (P <0.01), while TNF-α mRNA level and T-bet/GATA-3 ratio decreased in T group compared to N group (P <0.01).
CONCLUSIONXiaoyin Recipe for psoriasis could induce a Th1/Th2 balance drift toward Th2 in PBMC of EAT rats and thus improve the conditions.
Animals ; Autoantibodies ; blood ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; GATA3 Transcription Factor ; genetics ; metabolism ; Gene Expression Regulation ; drug effects ; Interleukin-10 ; genetics ; metabolism ; Psoriasis ; blood ; drug therapy ; immunology ; pathology ; Rats ; Rats, Wistar ; T-Box Domain Proteins ; genetics ; metabolism ; Th1-Th2 Balance ; drug effects ; Th2 Cells ; drug effects ; immunology ; Thyroiditis, Autoimmune ; blood ; drug therapy ; immunology ; pathology ; Tumor Necrosis Factor-alpha ; genetics ; metabolism
9.CMV-hFasL transgenic mice prevent from experimental autoimmune thyroiditis.
Zhen-lin ZHANG ; Bo LIN ; Lu-yang YU ; Li-he GUO
Chinese Medical Journal 2005;118(13):1087-1092
BACKGROUNDPrevious studies showed that the role of Fas ligand (FasL) is not consistent in the pathogenesis of autoimmune thyroiditis. This study was designed to investigate the effects of FasL on the pathogenesis of experimental autoimmune thyroiditis (EAT) using CMV-human FasL (hFasL) transgenic mice.
METHODSTransgenic mice ubiquitously expressing hFasL were used as an animal model of EAT by injection of porcine thyroglobulin (pTg). Expression of hFasL was detected by RT-PCR and Western blot. The activity of hFasL transgenic thyrocytes killing Jurket cells was determined. CMV-hFasL transgenic mice and wild type (WT) mice were immunized with pTg and killed 28 days later to evaluate the lymphocytic infiltration of their thyroids. The number of CD4+ and CD8+ lymphocytes from the spleen was detected using FACS. The serum interferon-gamma (IFN-gamma) concentration was measured by ELISA.
RESULTShFasL expression in the thyroid of CMV-hFasL transgenic mice was confirmed. After co-incubation of Jurket thymocytes with thyroid tissues of CMV-hFasL transgenic mice, the percentage of apoptotic cells in the CMV-hFasL transgenic thyroid group was significantly higher than that of the control WT thyroid group [(23.4 +/- 4.3)% vs (6.6 +/- 2.5)%, P < 0.01]. On day 28 after immunization with pTg, the infiltration index of lymphocytes in thyroids of the CMV-hFasL transgenic mice was significantly lower than that of the WT mice [(1.0 +/- 0.5) vs (2.1 +/- 0.7), P < 0.001]. Moreover, the number of CD4+ and CD8+ lymphocytes of the spleen and serum IFN-gamma concentration were significantly decreased in the CMV-hFasL transgenic mice.
CONCLUSIONSFasL plays an important role in the pathogenesis of autoimmune thyroiditis. Transgenic mice ubiquitously expressing hFasL may strongly inhibit lymphocytic infiltration of the thyroid of EAT and ameliorate the course of this disease.
Animals ; Blotting, Western ; CD4-CD8 Ratio ; Cytomegalovirus ; genetics ; Fas Ligand Protein ; Female ; Humans ; Interferon-gamma ; blood ; Jurkat Cells ; Membrane Glycoproteins ; physiology ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Promoter Regions, Genetic ; Reverse Transcriptase Polymerase Chain Reaction ; Thyroid Gland ; metabolism ; Thyroiditis, Autoimmune ; immunology ; prevention & control