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Cytokines and growth factors participate in immune responses, and the pathogenesis of autoimmune diseases. Herein, we simultaneously examined differential levels of 29 circulating factors to determine their associations in female patients with overt autoimmune thyroid disease (AITD). We enrolled 40 patients with Graves’ disease (GD), 20 patients with Hashimoto’s thyroiditis (HT), and 14 healthy controls. Twenty-nine circulating factors were simultaneously measured. GD patients with low thyroid-stimulating hormone at the time of sample collection were defined as having active GD. B-cell activating factor (BAFF) levels were associated with GD and HT (p = .001 and .001, respectively) and interferon (IFN)-α levels were higher in the HT group than in the control group (p = .021). Significant associations of serum BAFF and tumour necrosis factor (TNF)-α levels with free thyroxin (FT4) were present in HT (r = −0.498, p = .026, and r = 0.544, p = .013, respectively). Meanwhile, there were significant associations of FT4 with interleukin (IL)-4 and eotaxin levels in GD (r = 0.354, p = .025 and r = 0.384, p = .014, respectively). In active GD, serum BAFF and eotaxin level were correlated with FT4 levels (r = 0.465, p = .034, and r = 0.463, p = .035, respectively). In conclusion, BAFF is the best circulating indicator to identify GD and HT among all chosen 29 biomarkers, and it could be used to predict the disease severity in HT and active GD. Meanwhile, IFN-α could be another reliable parameter for recognising HT.

Autoimmune thyroid diseases (AITDs), including Hashimoto’s disease (HD) and Graves’ disease (GD), are archetypes of organ-specific autoimmune diseases, but the prognosis of patients with AITD varies. Autoimmune diseases, including AITDs, are believed to develop in response to both genetic and environmental factors. Interleukin (IL)-6 plays a major role in B cell differentiation and T cell proliferation, and methylation of the IL6 gene is associated with IL-6 production. To clarify the role of IL6 gene methylation in the pathogenesis and prognosis of AITDs, we measured the methylation levels of −666, −664, −610, −491 and −426 CpG sites in the IL6 gene. We measured the methylation levels of 5 CpG sites in 29 patients with HD, 31 patients with GD and 16 healthy volunteers using pyrosequencing. The methylation level at each of the −664, −491 and −426 CpG sites was negatively correlated with the age at the time of sampling. Multiple regression analysis indicated that patients with HD, including severe or mild HD, showed higher methylation levels at the −426 CpG site than control subjects. Patients with intractable GD showed lower methylation levels at the −664 and −666 CpG sites than patients with GD in remission. In conclusion, IL6 gene methylation levels were related to the susceptibility to HD and the intractability of GD.

Non-alcoholic fatty liver disease (NAFLD) has been studied with inflammation and immune, but the link with thyroid autoimmunity is unreported. This study aimed to explore the direct association of NAFLD with thyroid autoimmune disease (AITD) among participants with normal thyroid stimulating hormone (TSH) levels. The data were obtained from a cross-sectional study (SPECT-China). A total of 7982 participants were enrolled. Participants underwent several checkups including peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb), thyroid, and liver ultrasonography (US). The prevalence of NAFLD was higher in TPOAb and/or TgAb positive [TPO/TgAb (+)] group and TPOAb and/or TgAb together with US positive [TPO/TgAb (+) and US (+)] group for both genders. After full adjustment, binary logistic analysis showed the presence of NAFLD was positively associated with the serum level of TPOAb in men (p

Background: The aim was to determine prevalence and age at seroconversion of thyroid autoimmunity in relation to islet autoantibodies, gender and HLA-DQ genotypes in children with increased risk for type 1 diabetes followed from birth. Methods: In 10-year-old children (n = 1874), blood samples were analysed for autoantibodies against thyroid peroxidase (TPOAb), thyroglobulin (TGAb), glutamic acid decarboxylase 65 (GADA), Zink transporter 8 (ZnT8R/W/QA), insulinoma-associated protein-2 (IA-2A), insulin (IAA) and HLA-DQ genotypes. Prospectively collected samples from 2 years of age were next analysed for TPOAb, and TGAb and, finally, in confirming samples at 11–16 years of age along with TSH and FT4. Frequencies were tested with Chi-square or Fischer’s exact tests, autoantibody levels with Wilcoxon and correlations between autoantibody levels with Spearman’s rank correlation test. Results: The prevalence of thyroid autoimmunity was 6.9%, overrepresented in girls (p

Cytokines and growth factors participate in immune responses, and the pathogenesis of autoimmune diseases. Herein, we simultaneously examined differential levels of 29 circulating factors to determine their associations in female patients with overt autoimmune thyroid disease (AITD). We enrolled 40 patients with Graves' disease (GD), 20 patients with Hashimoto's thyroiditis (HT), and 14 healthy controls. Twenty-nine circulating factors were simultaneously measured. GD patients with low thyroid-stimulating hormone at the time of sample collection were defined as having active GD. B-cell activating factor (BAFF) levels were associated with GD and HT (p =.001 and.001, respectively) and interferon (IFN)-α levels were higher in the HT group than in the control group (p =.021). Significant associations of serum BAFF and tumour necrosis factor (TNF)-α levels with free thyroxin (FT4) were present in HT (r = −0.498, p =.026, and r = 0.544, p =.013, respectively). Meanwhile, there were significant associations of FT4 with interleukin (IL)-4 and eotaxin levels in GD (r = 0.354, p =.025 and r = 0.384, p =.014, respectively). In active GD, serum BAFF and eotaxin level were correlated with FT4 levels (r = 0.465, p =.034, and r = 0.463, p =.035, respectively). In conclusion, BAFF is the best circulating indicator to identify GD and HT among all chosen 29 biomarkers, and it could be used to predict the disease severity in HT and active GD. Meanwhile, IFN-α could be another reliable parameter for recognising HT. [ABSTRACT FROM AUTHOR]

The microRNA (miRNA) biogenesis pathway is regulated by specific proteins and enzymes, including Dicer, Drosha, DGCR8, Exportin 5 and the Argonaute (AGO) family. In this study, we investigated the AGO family, which is the primary component of RISC (RNA-induced silencing complex) and directly binds to microRNA. We examined the association of polymorphisms in AGO family genes with AGO expression and with the development and prognosis of autoimmune thyroid diseases. We genotyped AGO1 rs636832A/G, AGO2 rs7005286C/T, AGO2 rs11166985A/G and AGO2 rs2292779C/G polymorphisms in 184 Graves’ disease (GD) patients, 195 Hashimoto’s disease (HD) patients and 122 healthy volunteers using the polymerase chain reaction-restriction fragment length polymorphism method. We also examined the expression of AGO1 and AGO2 mRNAs in peripheral blood mononuclear cells (PBMC) obtained from 52 GD patients, 41 HD patients, and 25 healthy volunteers using quantitative RT-PCR methods. The G allele of AGO1 rs636832 and the A allele of AGO2 rs11166985 polymorphisms were significantly more frequent in GD patients than in healthy controls. The A allele of AGO2 rs11166985 was also significantly more frequent in intractable GD patients than in controls. The C carrier (CC + CG genotypes) and C allele of AGO2 rs2292779 polymorphism were significantly more frequent in intractable GD patients than in patients with GD in remission. Expression of AGO1 mRNA in PBMC was significantly higher in AITD patient than in controls, and that of AGO2 mRNA in PBMC was significantly higher in intractable GD patients than in patients with GD in remission. Furthermore, the expression levels of both the AGO1 and AGO2 genes were significantly correlated with the proportions of Th17 cells in PBMC. In conclusion, the polymorphisms of the AGO1 and AGO2 genes, the expression levels of which correlated with the proportion of Th17 cells, were associated with the development and prognosis of GD. The AGO2 rs2292779 C carrier and C allele were associated with the intractability of GD.

Introduction: The aim of the study was to assess serum levels of sFasL as a marker of thyroid dysfunction in children with autoimmune thyroid disease (AITD). Design: The group comprised 45 newly diagnosed children with Hashimoto’s thyroiditis and Graves’ disease versus euthyroid control group: 11 with hypothyroidism (10 girls and 1 boy, aged 12.2 ± 1.9 years), 19 children with hyperthyroidism (15 girls and 4 boys, aged 12.4 ± 4.9 years) and 15 healthy subjects (7 girls and 8 boys, aged 10.5 ± 4.8 years). Methods: Thyroid function (TSH, fT4, fT3), autoimmune (ATG, ATPO, TRAb) and anthropometric (weight, height, BMI, BMI-SDS, Cole index) parameters were evaluated. sFasL concentration was measured by ELISA. Nonparametric statistical test and ROC analysis were performed to assess the data. Results: We found no significant differences in serum concentrations of sFasL between boys and girls in the studied groups. Significantly higher sFasL levels (median 0.26 ng/ml) were identified in children with hypothyroidism compared with the control group (median 0.06 ng/ml, p

Autoimmune thyroid diseases (AITDs), including Hashimoto's disease (HD) and Graves' disease (GD), are archetypes of organ-specific autoimmune diseases, but the prognosis of patients with AITD varies. Autoimmune diseases, including AITDs, are believed to develop in response to both genetic and environmental factors. Interleukin (IL)-6 plays a major role in B cell differentiation and T cell proliferation, and methylation of the IL6 gene is associated with IL-6 production. To clarify the role of IL6 gene methylation in the pathogenesis and prognosis of AITDs, we measured the methylation levels of −666, −664, −610, −491 and −426 CpG sites in the IL6 gene. We measured the methylation levels of 5 CpG sites in 29 patients with HD, 31 patients with GD and 16 healthy volunteers using pyrosequencing. The methylation level at each of the −664, −491 and −426 CpG sites was negatively correlated with the age at the time of sampling. Multiple regression analysis indicated that patients with HD, including severe or mild HD, showed higher methylation levels at the −426 CpG site than control subjects. Patients with intractable GD showed lower methylation levels at the −664 and −666 CpG sites than patients with GD in remission. In conclusion, IL6 gene methylation levels were related to the susceptibility to HD and the intractability of GD. [ABSTRACT FROM AUTHOR]

Background: The aim was to determine prevalence and age at seroconversion of thyroid autoimmunity in relation to islet autoantibodies, gender and HLA-DQ genotypes in children with increased risk for type 1 diabetes followed from birth. Methods: In 10-year-old children (n = 1874), blood samples were analysed for autoantibodies against thyroid peroxidase (TPOAb), thyroglobulin (TGAb), glutamic acid decarboxylase 65 (GADA), Zink transporter 8 (ZnT8R/W/QA), insulinoma-associated protein-2 (IA-2A), insulin (IAA) and HLA-DQ genotypes. Prospectively collected samples from 2 years of age were next analysed for TPOAb, and TGAb and, finally, in confirming samples at 11-16 years of age along with TSH and FT4. Frequencies were tested with Chi-square or Fischer's exact tests, autoantibody levels with Wilcoxon and correlations between autoantibody levels with Spearman's rank correlation test. Results: The prevalence of thyroid autoimmunity was 6.9%, overrepresented in girls (p < .001) also having higher TPOAb levels at 10 years (p = .049). TPOAb was associated with GADA (p = .002), ZnT8R/W/QA (p = .001) and IA-2A (p = .001) while TGAb were associated with ZnT8R/W/QA (p = .021). In boys only, TPOAb were associated with GADA (p = .002), IA-2A (p = .001), ZnT8R/W/QA (p = .001) and IAA (p = .009), and TGAb with GADA (p = .013), IA-2A (p = .005) and ZnT8R/W/QA (p = .003). Levels of IA-2A correlated to both TPOAb (p = .021) and to TGAb (p = .011). In boys only, levels of GADA and TGAb correlated (p = .009 as did levels of IA-2A and TPOAb (p = .013). The frequency and levels of thyroid autoantibodies increased with age. At follow-up, 22.3% had abnormal thyroid function or were treated with thyroxine. Conclusions: Thyroid autoimmunity and high TPOAb levels were more common in girls. In contrast, in boys only, there was a strong association with as well as correlation between levels of thyroid and islet autoantibodies. It is concluded that while girls may develop autoimmune thyroid disease (AITD) independent of islet autoantibodies, the risk for thyroid disease in boys may be linked to concomitant islet autoimmunity. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) has been studied with inflammation and immune, but the link with thyroid autoimmunity is unreported. This study aimed to explore the direct association of NAFLD with thyroid autoimmune disease (AITD) among participants with normal thyroid stimulating hormone (TSH) levels. The data were obtained from a cross-sectional study (SPECT-China). A total of 7982 participants were enrolled. Participants underwent several checkups including peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb), thyroid, and liver ultrasonography (US). The prevalence of NAFLD was higher in TPOAb and/or TgAb positive [TPO/TgAb (+)] group and TPOAb and/or TgAb together with US positive [TPO/TgAb (+) and US (+)] group for both genders. After full adjustment, binary logistic analysis showed the presence of NAFLD was positively associated with the serum level of TPOAb in men (p < .001) and TgAb in women (p = .001). Both TPO/TgAb (+) and TPO/TgAb (+) and US (+) were associated with an increased risk of NAFLD in both genders [TPO/TgAb (+): odds ratio (OR) 1.474, 95% confidence interval (CI) 1.102, 1.970 in men and OR 1.308, 95%CI 1.061, 1.612 in women; TPO/TgAb (+) and US (+): OR 1.796, 95%CI 1.143, 2.820 in men and OR 1.380, 95%CI 1.058, 1.801 in women]. Thus, we got a conclusion that the prevalence of NAFLD was positively associated with the level and the positivity of TPOAb and TgAb among participants with normal TSH levels. This is the first report suggesting that there might exist common pathways in the pathogenesis of NAFLD and thyroid autoimmunity. [ABSTRACT FROM AUTHOR]

The microRNA (miRNA) biogenesis pathway is regulated by specific proteins and enzymes, including Dicer, Drosha, DGCR8, Exportin 5 and the Argonaute (AGO) family. In this study, we investigated the AGO family, which is the primary component of RISC (RNA-induced silencing complex) and directly binds to microRNA. We examined the association of polymorphisms in AGO family genes with AGO expression and with the development and prognosis of autoimmune thyroid diseases. We genotypedAGO1rs636832A/G,AGO2rs7005286C/T,AGO2rs11166985A/G andAGO2rs2292779C/G polymorphisms in 184 Graves’ disease (GD) patients, 195 Hashimoto’s disease (HD) patients and 122 healthy volunteers using the polymerase chain reaction-restriction fragment length polymorphism method. We also examined the expression ofAGO1andAGO2mRNAs in peripheral blood mononuclear cells (PBMC) obtained from 52 GD patients, 41 HD patients, and 25 healthy volunteers using quantitative RT-PCR methods. The G allele ofAGO1rs636832 and the A allele ofAGO2rs11166985 polymorphisms were significantly more frequent in GD patients than in healthy controls. The A allele ofAGO2rs11166985 was also significantly more frequent in intractable GD patients than in controls. The C carrier (CC + CG genotypes) and C allele ofAGO2rs2292779 polymorphism were significantly more frequent in intractable GD patients than in patients with GD in remission. Expression ofAGO1mRNA in PBMC was significantly higher in AITD patient than in controls, and that of AGO2 mRNA in PBMC was significantly higher in intractable GD patients than in patients with GD in remission. Furthermore, the expression levels of both theAGO1andAGO2genes were significantly correlated with the proportions of Th17 cells in PBMC. In conclusion, the polymorphisms of theAGO1andAGO2genes, the expression levels of which correlated with the proportion of Th17 cells, were associated with the development and prognosis of GD. TheAGO2rs2292779 C carrier and C allele were associated with the intractability of GD. [ABSTRACT FROM PUBLISHER]

Introduction: The aim of the study was to assess serum levels of sFasL as a marker of thyroid dysfunction in children with autoimmune thyroid disease (AITD).Design: The group comprised 45 newly diagnosed children with Hashimoto’s thyroiditis and Graves’ disease versus euthyroid control group: 11 with hypothyroidism (10 girls and 1 boy, aged 12.2 ± 1.9 years), 19 children with hyperthyroidism (15 girls and 4 boys, aged 12.4 ± 4.9 years) and 15 healthy subjects (7 girls and 8 boys, aged 10.5 ± 4.8 years).Methods: Thyroid function (TSH, fT4, fT3), autoimmune (ATG, ATPO, TRAb) and anthropometric (weight, height, BMI, BMI-SDS, Cole index) parameters were evaluated. sFasL concentration was measured by ELISA. Nonparametric statistical test and ROC analysis were performed to assess the data.Results: We found no significant differences in serum concentrations of sFasL between boys and girls in the studied groups. Significantly higher sFasL levels (median 0.26 ng/ml) were identified in children with hypothyroidism compared with the control group (median 0.06 ng/ml,p < 0.001) and in comparison to a group of children with hyperthyroidism (median 0.14 ng/ml,p < 0.05). ROC analysis indicates that sFasL effectively discriminated hypothyroid and healthy children (area under the curve/AUC = 0.897;p < 0,001; sensitivity: 100%, specificity: 73.3%), as well as both clinically opposing states: hyperthyroidism and hypothyroidism among themselves (AUC = 0.833;p= 0,003; sensitivity: 94,7%, specificity: 72.7%).Conclusions: Our work shows that sFasL may be useful marker in the assessment of thyroid dysfunction in children with autoimmune thyroid disease. [ABSTRACT FROM PUBLISHER]

Dicer and Drosha are RNase III enzymes that are necessary for the biogenesis of most miRNAs. However, there are no reports on the association of Dicer and Drosha with the pathogenesis of autoimmune thyroid disease (AITD). We genotypedDICERrs3742330A/G and rs1057035T/C as well asDROSHArs644236C/T and rs10719C/T polymorphisms in 255 Hashimoto's disease (HD) patients, in 255 Graves' disease (GD) patients and in 128 healthy controls by the polymerase chain reaction (PCR)- restriction fragment length polymorphism (RFLP) method. We also examined the expression ofDICERandDROSHAgene in peripheral blood mononuclear cells (PBMCs) by quantitative RT-PCR (qRT-PCR) methods. The TT genotype of theDICERrs1057035 polymorphism was less frequent in GD patients (p = 0.0098) than in healthy subjects. The CC genotype ofDROSHArs644236 polymorphism were more frequent in GD patients than in HD patients (p = 0.0171). The gene expression ofDICERwas lower in patients with AITD compared with that in control subjects (p = 0.0064) and was lower in patients with GD in remission than in patients with intractable GD (p = 0.0213). In addition, the expression ofDROSHAwas lower in patients with AITD than that in control subjects (p < 0.0001) and was lower in patients with severe HD than in patients with mild HD (p = 0.0440). In conclusion, theDICERrs1057035 TT genotype andDROSHArs644236 CC genotype were associated with the development of GD and the differentiation between GD and HD, respectively. The expression levels ofDICERandDROSHAgenes were low in AITD and differed depending on the intractability of GD and the severity of HD, respectively. [ABSTRACT FROM AUTHOR]

Chemokines induce leukocyte chemotaxis and contribute to chronic inflammation. To clarify the association between functional polymorphisms in genes encoding some chemokines and the pathogenesis of Autoimmune thyroid disease (AITD), we genotypedIL8−251T/A, Regulated upon Activation, Normal T cell Expressed and presumably Secreted (RANTES) − 403G/A, −28C/G,MIGrs2276886G/A,IP10−1596C/T, Monocyte Chemoattractant Protein1 (MCP1) − 2518G/A andIL16−295T/C polymorphisms. We genotyped these polymorphisms using the PCR-RFLP method in 149 Graves’ disease (GD) patients, including 59 patients with intractable GD and 53 patients with GD in remission, as well as 131 Hashimoto’s disease (HD) patients, including 54 patients with severe HD, 46 patients with mild HD and 99 healthy controls. TheIL8−251TT genotype andMIGrs2276886 A allele were more frequent in patients with AITD (p = 0.0139 andp = 0.0005, respectively). TheRANTES − 403AA and −28GG genotypes were less frequent in patients with AITD (p = 0.0164 andp = 0.0221, respectively). TheMCP1−2518GG genotype was more frequent in HD patients (p = 0.0323). TheMIGrs2276886 AG genotype was less frequent in patients with intractable GD (p = 0.0051). Interestingly, the age of onset in GD patients with theRANTES − 28CC genotype was younger than in those with −28CG and GG genotypes (p = 0.0028). In this study, we first reported that the polymorphisms inIL8, RANTESandMIGgenes are associated with the development of AITD, and that theMIGrs2276886 AG genotype is associated with the intractability of GD. TheRANTES − 28CC genotype is associated with young onset of GD. [ABSTRACT FROM PUBLISHER]

Former studies have revealed the link between the tumor necrosis factor (TNF) receptor-associated factor 1 (TRAF1) polymorphisms and autoimmunity. In the present study, we took an opportunity to investigate the association between TRAF1 and autoimmune thyroid disease (AITD) in order to find a new susceptibility gene. A total of 1029 AITD patients [677 Graves’ disease (GD) patients and 352 Hashimoto thyroiditis (HT) patients] and 899 controls were enrolled. We used matrix-assisted laser desorption ionization-time of flight mass spectrometer (MALDI-TOF-MS) to detect the polymorphisms of rs4836834, rs10760130, rs10818488, rs2239658, rs2900180. We also explored the association between polymorphisms and clinical subphenotypes. Genotype frequencies of the five loci in all AITD patients were significantly different from those of controls. Genotype frequencies of rs10760130, rs2239658 and rs2900180 in GD patients were significantly different from controls. Allele analysis found that T allele of rs4836834, G allele of rs10760130, A allele of rs10818488, T allele of rs2239658 and T allele of rs2900180 were significantly higher in GD and AITD patients. No significant differences were found between HT patients and controls. Haplotype analysis found three haplotypes including ACAGC, TTGAT and TCGAC. ACAGC frequencies were significantly lower in GD and HT patients. However, TTGAT frequency was only significantly higher in GD patients. No significant results were found between polymorphisms and clinical subphenotypes. Our study reveals TRAF1 as a susceptibility gene of AITD in Chinese Han population. [ABSTRACT FROM PUBLISHER]

Autoimmune thyroid disease (AITD) is a multifactorial organ-specific autoimmune disorder, and both genetic susceptibility and environmental factors are involved in its etiology. TNFAIP3 encodes the ubiquitin-modifying enzyme (A20), a key regulator of inflammatory signaling pathways. The aim of the present study was to evaluate the association between TNFAIP3 gene polymorphisms and AITD in Chinese Han population. Three single nucleotide polymorphisms (SNPs) in TNFAIP3 gene locus (rs598493, rs610604 and rs661561) were detected in a set of 667 patients with AITD and 301 controls in Han Chinese population using the Matrix Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometer (MALDI-TOF-MS) Platform. Compared with those of the controls, the frequencies of GG genotype of rs598493, the AA genotype of rs610604, the allele G and GG genotype of rs661561 were significantly increased in Graves' disease (GD) patients. However, the frequencies of AG genotype of rs598493 and AC genotype of rs610604 were significantly decreased in GD patients. The ATC haplotype (rs598493, rs661561 and rs610604) was associated with a decreased risk of GD. No significant differences in the three SNPs were observed between HT patients and controls. Our study shows a clear association between the polymorphisms of TNFAIP3 gene and GD, not HT, suggesting that TNFAIP3 gene is likely to be a genetic susceptibility factor to GD. [ABSTRACT FROM AUTHOR]

A study of IgG4 autoantibody levels in juvenile thyroid disease patients showed evidence of heritability using the ROMP screening method. These levels increased with time despite the fact that total IgG antibody decreased with time. Evidence of heritability was demonstrated only in patients with high titers of autoantibodies to both thyroglobulin (Tg) and thyroperoxidase (TPO) unlike family members who may show high titers of one or the other and be asymptomatic at the time of sampling. Since high and low IgG4 levels give different heritability plots, these findings may represent a more severe fibrotic form of thyroiditis with a distinct genetic background. Hence a simple predictive approach is offered by this screening tool for the disease in patients and family members which may be helpful in the future to identify IgG4-related thyroiditis early in the course of disease without the requirement for biopsy. [ABSTRACT FROM AUTHOR]

Using a simple screening technique called regression of offspring on mid-parent (ROMP) to examine the role of IgG subclasses in affected and unaffected siblings of children and adolescents with autoimmune thyroid disease and their parents, both total-restricted and subclass-restricted autoantibodies to thyroglobulin (Tg) were assayed quantitatively for each of the IgG subclasses. There was a significant correlation of anti-Tg titer of probands with parental titers in thyrotoxicosis (TT), ( R2  ==  0.569, p  ==  0.001), but not in chronic lymphocytic thyroiditis. The most striking correlation was in TT patients of African-American ancestry, ( R2  ==  0.9863, p  ==  0.0007). Additional insight is provided by examining the contributions of the IgG subclasses individually, particularly those whose concentrations appear not to have direct influence on the total IgG titers. Thus, using small numbers of patients, and assaying the IgG subclass distributions, as well as any other immunoglobulin isotypes that are significantly altered in autoantibody assays, ROMP can be performed rapidly to ascertain which quantifiable parameters may be usefully extended to predict disease onset and progression. [ABSTRACT FROM AUTHOR]

Thyroid peroxidase antibodies (TPOAbs) in patients with Hashimoto's thyroiditis (HT) predominantly react with two immunodominant regions (IDR-A, IDR-B). Theoretically, as shown for the level of TPOAbs, the autoantibody epitopic recognition of the IDRs could be under genetic control. To examine this, we compared the distribution of TPOAb epitopic fingerprints between healthy monozygotic (MZ) co-twins and siblings to patients with clinically overt HT with a control group of euthyroid subjects, matched for sex and age, but without autoimmune thyroid disease (AITD) among their first-degree relatives. Two ELISAs based on competition with rabbit antisera were used to determine the IDR specificities in 23 patients with HT, 6 MZ co-twins, 8 siblings to patients with HT, and 11 healthy euthyroid subjects without predisposition to AITD. The fraction of TPOAbs recognizing IDR-A was 19, 18, and 9% in HT patients, MZ-co-twins, and siblings, respectively, which was higher than the 0% found in the group of healthy subjects without predisposition to AITD ( p  ==  0.007 vs. HT; p  ==  0.1078 vs. MZ co-twin and p  ==  0.069 vs. siblings). Moreover, the IDR-A fraction differed between healthy MZ-co-twins and ordinary siblings (18% vs. 9%, p  ==  0.0127). In conclusion, our data indicate that the propensity to produce autoantibodies directed against the IDR-A epitope of TPO is genetically determined. This finding may have implications with respect to inheritance of autoantibody specificities in other autoimmune diseases. [ABSTRACT FROM AUTHOR]

We analyzed three functional 5' un-translated region β-defensin 1 (DEFB1) single nucleotide polymorphism (SNPs) in a group of 170 type 1 diabetes (T1D) patients. In order to evaluate the SNPs influence on the disease onset and the development of other autoimmune disorder, such as celiac disease (CD) and autoimmune thyroid disease (AITD), patients were stratified according to the presence of AITD, CD, and both AITD and CD. As control group, we studied 191 healthy children and adolescent not presenting a familiar historic of T1D, CD or AITD. DEFB1 SNPs were in Hardy-Weinberg equilibrium both in healthy controls and T1D patients, as well in the T1D patients stratified according to the presence of other autoimmune disorder(s). Allele, genotype, and haplotype frequencies of T1D patients globally considered were comparable to healthy controls ones. No evidence of any association of DEFB1 SNPs with the onset of AIDT, CD, and both AITD and CD on T1D patients was evidenced. Only a minor trend was found for an increased frequency of the - 20 G allele in T1D patients only presenting AITD vs. T1D patients not presenting AITD or CD, as well as an increase of those haplotypes comprising the - 20 G allele when compared with the GCA haplotype. We also evaluated the influence of functional DEFB1 SNPs on the age of T1D onset: no significant statistical conclusion was achieved. Further studies are envisaged, in order to elucidate the possible role of functional DEFB1 polymorphisms in the onset of TD1 and other autoimmune-related disorders. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to assess thyroid function as well as the prevalence and clinical value of anti-thyroid antibodies in patients with rheumatoid arthritis (RA). Methods: Seventy patients with active RA (ACR criteria), 9 males and 61 females, mean age 47 years (range 15-77) were analyzed. Anti-thyroperoxidase (TPOAb) and anti-thyroglobulin antibodies (TgAb) were tested using radioimmunoassay. Free thyroxine (FT4) and free triiodothyronine (FT3) and thyroid-stimulating hormone (TSH) serum levels were measured using electro-immunochemiluminescence (ECLIA, Elecsys Roche). Clinical variables, including tender and swollen joint count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), anti-cyclic citrullinated peptide antibody (anti-CCP) and antinuclear antibodies (ANA) were also evaluated. Statistics were performed by the SPSS statistical software for Windows. Results: Twenty-six patients (37%) with RA were positive for TPOAb and 16 (23%) for TgAb. In 5 (7.1%) patients TSH level was slightly elevated, ranging between 4.52 and 15.65 UI/ml. The increase of TSH levels was associated with normal FT4 in 3 cases (4.2%) and with reduced FT4 in 2 cases (2.8%). One patient (1.5%) had low TSH serum value along with normal FT4. No differences in clinical and serological data between anti-thyroid positive and negative patients were observed. Conclusion: Our study shows an increased prevalence of anti-thyroid antibodies in RA patients with a low prevalence of hormonal alterations. However, anti-thyroid antibodies do not seem to identify any peculiar RA phenotype. [ABSTRACT FROM AUTHOR]

The role of cytokines in the pathogenesis of autoimmune thyroid disease (ATD) has been extensively investigated over the past years. In patients with ATD, these molecules can be found in both the thyroid and sites of extrathyroidal complications of the disease. Cytokines can affect the autoimmune process through a number of mechanisms including recruitment of inflammatory cells and upregulation of molecules essential for perpetuation of the inflammatory response in the affected site. In addition, cytokines can interfere with thyroid hormone synthesis, implicating them directly in thyroid dysfunction found in ATD patients. Also, these molecules can modulate the function of cells in orbital tissue, which results in localised oedema, indicating a central role for cytokines in the development of proptosis, the cardinal feature of thyroid associated ophthalmopathy. [ABSTRACT FROM AUTHOR]

Monoclonal antibody (MAbs) is a powerful and essential tool to perform studies concerning antigens and antibodies at molecular level. MAbs to major thyroid specific autoantigens, thyroglobulin (Tg), thyroid peroxidase (TPO) and TSH receptor (TSHR), have been prepared and applied for a variety of investigations including the structure of antigens and antibodies, the expression of antigens, the epitopes of antibodies, the functional regions of antigens, mutated antigens in congenital diseases, and clinical applications to diagnosis of various thyroid diseases. Recently, sodium iodide symporter (NIS) was identified and became a potential thyroid autoantigen related to autoimmune thyroid disease, although few MAbs to NIS have been prepared. In this manuscript, I primarily focus on studies concerning MAbs to three major thyroid specific autoantigens, Tg, TPO and TSHR, and summarize studies using the mAbs. [ABSTRACT FROM AUTHOR]

To determine the prevalence of autoimmune thyroid disease (AITD) in children and adolescents with type 1 diabetes mellitus (DM), and assess whether the development of AITD is correlated with specific DQ-A and DQ-B loci of the HLA class II antigens, we analyzed thyroid function using anti-thyroid antibodies and HLA-DQ-A and -DQ-B polymorphisms in 69 patients with type 1 DM, in 75 normal healthy controls, and in 21 patients with AITD but without type 1 DM. Eighteen patients (26%) in the diabetic patients had AITD. In the diabetic patients, DQA1*0301 and DQB1*0302 occurred more frequently than in controls [DQA1*0301: OR=1.939, 95% CI=1.210-3.109 ( P =0.008, P c (corrected P ) <0.05); DQB1*0302: OR=2.558, 95% CI=1.354-4.832 ( P =0.005, P c >0.05 )]. Compared with controls, non-diabetic subjects with AITD showed higher frequency of DQA1*0301 ( P c <0.05) and DQB1*0601 ( P c >0.05), but these alleles were not contributing factors in the development of AITD in diabetic patients. In diabetic patients, DQB1*0201, known as susceptible allele of type 1 DM was not a contributing factor in the development of AITD in diabetic patients. Unlike DQB1*0201, DQB1*0401 was more frequently found in diabetic patients with AITD than in controls [ OR=4.053, 95% CI=1.607-10.221 ( P =0.0017, P c <0.05 )] or than in non-diabetic AITD patients [ OR=15.769, 95% CI=1.905-130.530 ( P =0.002, P c <0.05 )]. In non-diabetic subjects, DQB1*0401 did not provide susceptibility for AITD. Our results suggest that HLA DQB1*0401 is a predisposing genetic marker for the development of AITD in patients with type 1 DM in Korea. [ABSTRACT FROM AUTHOR]