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 ; *Genetic Linkage ; HLA-DR Antigens/*genetics ; Humans ; Korea ; Lymphotoxin-alpha/*genetics ; *Polymorphism, Genetic ; Receptors, Thyrotropin/*immunology ; Thyroiditis, Autoimmune/*genetics

Objectives, recent epidemiologic studies in humans suggest an increased prevalence of thyroiditis associated with the excessive administration of iodine. More than three times of recommended daily intake of iodine was observed among people in North America. These people generally presented higher level of anti-thyroglobulin antibody, anti-thyroperoxidase antibody, serum thyroid-stimulating hormone and exacerbation of lymphocytic infiltration in thyroid, which indicated the overconsumption of iodine could induce hypothyroidism and enhance the autoimmune response. However, the precise mechanism of excessive iodine intake induced autoimmune thyroid disease remains largely unknown. Over half a century has elapsed since the 1956 identification of thyroglobulin antibodies and the devising of the first experimental model of autoimmune thyroiditis. Since then an incredible amount of experimental work has led to an ever deeper understanding of the nature of thyroid auto-antigens, the main immune mechanisms responsible for Hashimoto's thyroiditis and graves' disease, their genetics, and therir environmental risk factor. Yet, in the majority of genetically predisposed people the individual trigger of thyroid autoimmunity remains obscure. Similarly, effective prevention strategies still remain to be established and, hopefully, will be the target of future studies.
Antibodies ; Autoimmunity ; Genetics ; Graves Disease ; Humans ; Hypothyroidism ; Iodine ; Models, Theoretical ; North America ; Prevalence ; Recommended Dietary Allowances ; Risk Factors ; Thyroglobulin ; Thyroid Diseases ; Thyroid Gland* ; Thyroiditis ; Thyroiditis, Autoimmune ; Thyrotropin

OBJECTIVETo study the immunoglobulin gene rearrangement patterns in Hashimoto's thyroiditis (HT) and primary thyroid lymphoma (PTL), and to analyze the relationship between the two diseases.

METHODSFormalin-fixed and paraffin-embedded tissues of 11 cases of PTL and 38 cases of HT as well as their clinical data, were retrieved. The latter group was further subcategorized into classic HT and suspicious PTL. Gene rearrangement studies for immunoglobulin heavy chains and light chains were carried out by polymerase chain reaction (PCR) using VH, FR3A and FR3kappa primers.

RESULTSThere was an increasing trend in immunoglobulin gene rearrangement rate for classic HT (10.7%), suspicious PTL (40.0%) and PTL (72.7%) groups. In general, a female predilection was observed. This sex predilection however was less obvious in the PTL group. There was no relationship between serum antibody (both thyroglobulin and thyroid peroxidase) titers and gene rearrangement patterns.

CONCLUSIONSHT and PTL show morphologic overlaps and may not be clearly distinguished on the basis of light microscopy alone. PCR-based immunoglobulin gene rearrangement study may be helpful in the detection of cases with early lymphomatous transformation of HT.

Female ; Gender Identity ; Gene Rearrangement ; Hashimoto Disease ; genetics ; Humans ; Lymphoma ; genetics ; pathology ; Male ; Middle Aged ; Sex Characteristics ; Thyroid Neoplasms ; genetics ; pathology ; Thyroiditis, Autoimmune ; genetics

OBJECTIVETo investigate the relationship between CYP27B1 gene promoter polymorphism and autoimmune thyroid diseases.

METHODSA case-control study including 158 patients with Graves' disease (GD), 174 patients with Hashimoto's thyroiditis (HT) and 172 matched controls was conducted. Three genotypes of CYP27 B1 gene -1260 site (CC, AA and AC) were determined by restriction fragment length polymorphism (PCR-RFLP) assay and confirmed by sequencing.

RESULTSThe genotypic distribution of CYP27 B1 gene-1260 site showed no deviation from Hardy-Weinberg equilibrium. The genotype and allele frequencies of -1260A/C were CC34.3%, AA19.2%, AC46.5%, C57.6%, and A42.4% in the control group, 48.1%, 13.3%, 38.6%, 67.4%, and 32.6% in GD group, and 47.1%, 10.3%, 42.5%, 68.4%, and 31.6% in HT group, respectively. Significant difference was found in the genotype and allele frequencies in -1260A/C polymorphism between GD and the control groups (Chi2=6.80, P<0.05 for genotype frequencies, and Chi2=6.79, P<0.05 for allele frequencies) and between HT and the control groups (Chi2=8.39, P<0.05 for genotype frequencies, and Chi2=8.71, P<0.05 for allele frequencies).

CONCLUSIONCYP27 B1 promoter -1260 polymorphism is associated with GD or HT in Chinese Han population.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase ; genetics ; Adolescent ; Alleles ; Child ; Female ; Gene Frequency ; Genotype ; Graves Disease ; genetics ; Hashimoto Disease ; genetics ; Humans ; Linkage Disequilibrium ; Male ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length ; Promoter Regions, Genetic ; genetics ; Thyroiditis, Autoimmune ; genetics

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

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