Cross-reaction of eye muscle antibodies with thyroid tissue in thyroid-associated ophthalmopathy

1989 ◽  
Vol 122 (1) ◽  
pp. 201-NP ◽  
Author(s):  
D. Weightman ◽  
P. Kendall-Taylor
Keyword(s):  
Thyroid Disease ◽  
Autoimmune Thyroid Disease ◽  
Thyroid Tissue ◽  
Cross Reaction ◽  
Antigenic Determinants ◽  
Enzyme Linked Immunosorbent Assay ◽  
Western Blots ◽  
Eye Muscle ◽  
Autoimmune Thyroid ◽  
Thyroid Associated Ophthalmopathy

ABSTRACT The nature of the association of ophthalmopathy with autoimmune thyroid disease is not understood. Serum autoantibodies to eye muscle have previously been identified and in this study we have explored the hypothesis that there may be shared antigenic determinants between orbital and thyroid tissues. Sera were obtained from patients in whom eye muscle antibodies (EMAb) had been detected by an enzyme-linked immunosorbent assay (ELISA); the sera were preincubated with membrane preparations of thyroid or eye muscle, hepatic membranes being used as control. Tissue-binding antibodies were removed from serum by centrifugation and the supernatant serum was analysed using an indirect ELISA and by immunoblotting. In the ELISA, all sera gave a positive response for EMAb. In one serum, the binding was entirely non-specific. All sera showed significant neutralization of EMAb by eye muscle. In six sera there was reduction of EMAb after exposure to thyroidal antigens, indicative of cross-reaction. Western blotting confirmed the non-specific nature of the binding in one serum. In five of the remaining nine sera, protein bands were identified which interacted specifically with eye muscle and, in two of these, the same determinants were neutralized by preincubation with thyroid tissue. The Western blots confirmed the findings in the ELISA. The determinants recognized by IgG were variable between patients and no common antigen could be identified. This study demonstrates that, in some cases of thyroid-associated ophthalmopathy, there is cross-reaction of EMAb with thyroidal antigens, but this is variable and not found in every case. This may explain the association of the disease with autoimmune thyroid disease, at least in some cases. Journal of Endocrinology (1989) 122, 201–206

scholarly journals Analysis of expression and function of the inhibitory receptor ILT2 in lymphocytes from patients with autoimmune thyroid disease

2011 ◽  
Vol 165 (1) ◽  
pp. 129-136 ◽  
Author(s):  
Lesly Doníz-Padilla ◽  
Amalia E Paniagua ◽  
Pilar Sandoval-Correa ◽  
Adriana Monsiváis-Urenda ◽  
Susanna Leskela ◽  
...  
Keyword(s):  
Thyroid Disease ◽  
Autoimmune Thyroid Disease ◽  
Cell Cycle Progression ◽  
Mononuclear Cells ◽  
Thyroid Tissue ◽  
Interleukin 10 ◽  
Regulatory Function ◽  
Peripheral Blood Mononuclear ◽  
Autoimmune Thyroid ◽  
And Function

ObjectiveAutoimmune thyroid disease (AITD) is characterized by different defects in immunoregulatory mechanisms. The immunoglobulin-like transcript receptor 2 (ILT2) or leukocyte Ig-like receptor 1 (LIRB1/CD85j) exerts an important immunoregulatory role. We hypothesized that the lymphocytes from AITD patients have a diminished expression and function of ILT2. The aim of this study was to investigate the expression and function of ILT2 in lymphocytes from patients with AITD.Design and methodsIn this study, 18 patients with Hashimoto's thyroiditis (HT), 20 with Graves' disease, and 26 healthy controls were studied. ILT2 expression was analyzed by flow cytometry and immunohistochemistry in peripheral blood mononuclear cells (PBMC) and thyroid tissue. The regulatory function of ILT2 was assessed by an assay of inhibition of lymphocyte proliferation and by an analysis of cell cycle progression. The effect of ILT2 on cytokine synthesis was also evaluated.ResultsWe found a significant increased expression of ILT2 by lymphocytes in AITD patients. ILT2 was also detected in the leukocyte infiltrate of thyroid tissue from HT patients. On the contrary, a significant diminished inhibitory activity of ILT2 on cell proliferation was observed in AITD patients. In addition, PBMC from AITD patients showed a diminished synthesis of interleukin 10 on ILT2 engagement.ConclusionsThe abnormal expression and function of ILT2 detected in AITD suggests that this receptor may participate in the pathogenesis of this condition.

scholarly journals Variants of Interleukin-22 Gene Confer Predisposition to Autoimmune Thyroid Disease

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Rong-hua Song ◽  
Qian Li ◽  
Wen Wang ◽  
Qiu-ming Yao ◽  
Xiao-qing Shao ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Thyroid Disease ◽  
Gene Polymorphisms ◽  
Autoimmune Thyroid Disease ◽  
Direct Sequencing ◽  
Autoimmune Thyroid ◽  
Interleukin 22 ◽  
Sequencing Method ◽  
Thyroid Associated Ophthalmopathy ◽  
Direct Sequencing Method

As there are no previous studies on the interleukin-22 (IL-22) variants in autoimmune thyroid disease (AITD), the present study aimed to explore the association between polymorphisms of IL-22 and the predisposition to AITD. The study had 975 AITD patients, including 639 Graves’ disease (GD) and 336 Hashimoto’s thyroiditis (HT) individuals and 851 healthy cohorts. Ligase detection reaction (LDR) and direct sequencing method were used for genotyping the IL-22 gene polymorphisms at rs2046068, rs2227478, rs2227485, rs11611206, and rs1179251. In comparison to female controls, genotype CC of rs1179251 was increased in the female AITD patients. Alleles C at rs2046068, C at rs2227478, and C at rs1179251 linked to the susceptibility of HT males. Genotype CC in rs1179251 was higher in male HT. Variants at rs2046068, rs2227478, and rs1179251 were associated with the AITD teenagers. Besides, genotype GG in rs11611206 was correlated with thyroid-associated ophthalmopathy (TAO). Moreover, allele G at rs11611206 was associated with decreased risk for TAO by 28.9%. Similarly, genotype CC of rs1179251 and genotype GG of rs11611206 were associated with Graves’ ophthalmopathy (GO). Allele G in rs11611206 increased people with HT towards the predisposition of hypothyroidism. In conclusion, genetic variants of IL-22 are associated with the occurrence of AITD.

Genetic Risk Factors for Autoimmune Thyroid Disease might Affect the Susceptibility to and Modulate the Progression of Primary Biliary Cholangitis

2017 ◽  
Vol 26 (3) ◽  
pp. 245-252 ◽  
Author(s):  
Aleksander Kuś ◽  
Magdalena Arłukowicz Grabowska ◽  
Konrad Szymański ◽  
Ewa Wunsch ◽  
Małgorzata Milkiewicz ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Thyroid Disease ◽  
Autoimmune Thyroid Disease ◽  
Clinical Course ◽  
Assay Method ◽  
Enzyme Linked Immunosorbent Assay ◽  
Primary Biliary Cholangitis ◽  
Thyroid Peroxidase ◽  
Genome Wide Association Studies ◽  
Autoimmune Thyroid

Background & Aims: Patients with primary biliary cholangitis (PBC) frequently suffer from extrahepatic autoimmune conditions, of which autoimmune thyroid disease (AITD) is one of the most common. Previous studies identified several genetic variants increasing the odds of developing AITD. Here we investigate whether AITD-associated polymorphisms might also play a role in the development and clinical course of PBC and PBC associated with AITD (PBC-AITD).Methods: To this end, we prospectively recruited 230 patients with PBC and 421 healthy controls. Among recruited patients, 64 (30.9%) had PBC-AITD as diagnosed by elevated serum TPO-antibodies. In all subjects we genotyped 10 variants previously associated with AITD.Results: We detected significant associations between the PTPN22 polymorphism and risk of developing PBC (rs2476601, OR=1.43, P=0.035) as well as PBC-AITD (OR=1.74, P=0.028). The IL2RA polymorphism was associated with liver cirrhosis (rs41295061, OR=1.76, P=0.033) whereas the MMEL1 polymorphism increased the risk of requiring liver transplantation (rs2843403, OR=1.70, P=0.023). Although no significant differences in clinical or biochemical characteristics between patients with PBC and PBC-AITD were seen (all P>0.05), liver function tests and metabolic traits in PBC patients were significantly (all P<0.05) affected by the CTLA4 (rs3087243), MMEL1 (rs2843403), PTPN22 (rs2476601) and RNASET2 (rs9355610) variants.Conclusion: Our study demonstrates the existence of a genetic overlap between PBC and AITD. Apparently, genetic variants known to increase the AITD risk might affect the clinical course of PBC. On the other hand, AITD per se does not seem to significantly influence the natural history of PBC.Abbreviations: AITD: autoimmune thyroid disease; ALP: alkaline phosphatase; ALT: alanine transaminase; AMA: anti-mitochondrial autoantibodies; AST: aspartate aminotransferase; DM1: diabetes mellitus type 1; ELISA: enzyme-linked immunosorbent assay method; GGT: gamma-glutamyl transpeptidase; GD: Graves’ disease; GWAS: genome-wide association studies; HT: Hashimoto thyroiditis; HWE: Hardy-Weinberg equilibrium; Lyp: lymphoid-specific protein tyrosine phosphatase non-receptor type 22; OR: odds ratio; PBC: primary biliary cholangitis; RA: rheumatoid arthritis; SLE: systemic lupus erythematosus; TPOAb: thyroid peroxidase antibody; UDCA: ursodeoxycholic acid.

scholarly journals Association of MICA Alleles with Autoimmune Thyroid Disease in Korean Children

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Won Kyoung Cho ◽  
Min Ho Jung ◽  
So Hyun Park ◽  
In Cheol Baek ◽  
Hee-Baeg Choi ◽  
...  
Keyword(s):  
Thyroid Disease ◽  
Autoimmune Thyroid Disease ◽  
Healthy Controls ◽  
Complex Class ◽  
Related Gene ◽  
Korean Children ◽  
Autoimmune Thyroid ◽  
Histocompatibility Complex ◽  
Thyroid Associated Ophthalmopathy ◽  
Nkg2d Receptor

Background. Major histocompatibility complex class I chain-related gene A (MICA) is a ligand for the activating NKG2D receptor expressed on natural killer (NK) cells. We aimed to assess the association of MICA polymorphism with autoimmune thyroid disease (AITD) in Korean children.Methods. Eighty-one patients with AITD were recruited. We analyzed MICA polymorphisms by PCR-SSP and compared the results with those of 70 healthy controls.Results. In AITD, the allele frequencies of MICA*010 (OR=2.21; 95% CI, 1.30–3.76,P<0.003,Pc<0.042) were higher than those of controls. Patients who did not have thyroid-associated ophthalmopathy showed higher frequencies of MICA*010 (OR=2.99; 95% CI, 1.47–6.08,P<0.003,Pc<0.042) and lower frequencies of MICA*008 (OR=0.08; 95% CI, 0.01–0.62,P<0.001,Pc<0.014) compared to those of controls. HLA-B*46, which shows the strongest association with AITD compared with other HLA alleles, showed the strongest linkage disequilibrium with MICA*010. Analyses of the associations between MICA*010 and HLA-B*46 with AITD suggest an association of the MICA allele with AITD.Conclusions. Our results suggest that innate immunity might contribute to the pathogenesis of AITD.

scholarly journals Association of Autoimmune Thyroid Disease with Anti-GAD Antibody ELISA Test Positivity and Risk for Insulin Deficiency in Slowly Progressive Type 1 Diabetes

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Masahito Katahira ◽  
Hidetada Ogata ◽  
Takahiro Ito ◽  
Tsutomu Miwata ◽  
Megumi Goto ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Thyroid Disease ◽  
Autoimmune Thyroid Disease ◽  
Enzyme Linked Immunosorbent Assay ◽  
Acid Decarboxylase ◽  
Insulin Deficiency ◽  
Autoimmune Thyroid ◽  
Progressive Type ◽  
Significant Difference

The presence of antiglutamic acid decarboxylase antibody (GADA) is required for the diagnosis of slowly progressive type 1 diabetes (SPT1D). We examined the factors influencing GADA determination by radioimmunoassay (GADA-RIA) and by enzyme-linked immunosorbent assay (GADA-ELISA). Sixty patients with SPT1D and 154 patients with type 2 diabetes were examined by both GADA-RIA and GADA-ELISA and for the presence of autoimmune thyroid disease (AITD). We compared the clinical characteristics of these patients based on the positivity or negativity of GADA-RIA and GADA-ELISA, and the existence or nonexistence of AITD. Thirty of 60 (50.0%) GADA-RIA-positive patients were GADA-ELISA negative, whereas none of the 154 GADA-RIA-negative patients were GADA-ELISA positive. Concomitant AITD was significantly less in patients with GADA-RIA and without GADA-ELISA and was significantly more in patients with GADA-RIA and GADA-ELISA. In GADA-RIA-positive patients, there was no significant difference in the GADA-RIA titer among the GADA-ELISA-negative patients with and without AITD, and the GADA-ELISA-positive patients without AITD; whereas the frequency of insulin deficiency was significantly higher in the patients with AITD and/or GADA-ELISA than in those without AITD and GADA-ELISA. Examination of GADA-ELISA and AITD in GADA-RIA-positive patients might be useful in predicting insulin deficiency in these patients.

scholarly journals SUN-724 Associations of GPR174 and ITM2A Genes on X Chromosome with Early Onset Autoimmune Thyroid Disease in Korean

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Nayeong Lee ◽  
Wonkyoung Cho ◽  
Hyeri Shin ◽  
Yoonji Lee ◽  
Seulki Kim ◽  
...  
Keyword(s):  
X Chromosome ◽  
Thyroid Disease ◽  
Autoimmune Thyroid Disease ◽  
Nucleotide Polymorphisms ◽  
Autoimmune Thyroid Diseases ◽  
Single Nucleotide ◽  
Korean Children ◽  
Autoimmune Thyroid ◽  
Thyroid Associated Ophthalmopathy ◽  
Immune Related Genes

Abstract Background: Autoimmune thyroid diseases (AITDs) are female predominant and the biology of sexual dimorphism is not clearly understood. Recently, GPR174 and ITM2A on X chromosome have been newly suggested as autoimmune thyroid disease susceptible loci. Methods: Fourteen single nucleotide polymorphisms in immune related genes on X chromosome were analyzed in 108 Korean children (girls =90, boys =18) with AITD [Hashimoto disease (HD) = 40, Graves′ disease (GD) = 68, thyroid-associated ophthalmopathy (TAO) = 37, and non-TAO =60] with gender ratio matched normal control 106 controls (female = 43, male = 63). Results: In AITD, the frequencies of GPR174 rs3810711 T allele (OR=6.0, cP =0.000), GRP174 rs3827440 T allele (OR=6.0, cP =0.000), ITM2A-GPR174 rs5912838 A allele (OR=2.7, cP =0.001) were increased and of GPR174 rs3810711 CC genotype (OR=0.2, cP =0.000), GRP174 rs3827440 CC genotype (OR=0.2, cP =0.000), ITM2A-GPR174 rs5912838 CC genotype (OR=0.4, cP =0.000)were lower than controls. In GD, the frequencies of GPR174 rs3810711 T allele (OR=8.4, cP =0.000), GRP174 rs3827440 T allele (OR=8.4, cP =0.000), ITM2A-GPR174 rs5912838 A allele (OR=3.3, cP =0.000) were increased and GPR174 rs3810711 CC genotype (OR=0.1, cP =0.000), C allele (OR=0.5, cP =0.044), GRP174 rs3827440 CC genotype (OR=0.2, cP =0.000), C allele (OR=0.5, cP =0.044), ITM2A-GPR174 rs5912838 CC genotype (OR=0.4, cP =0.000) were lower than controls. In HD, the frequencies of GPR174 rs3810711 T allele (OR=3.9, cP =0.003), GRP174 rs3827440 T allele(OR=3.9, cP =0.003) were increased and GPR174 rs3810711 CC genotype (OR=0.3, cP =0.004), rs3827440 CC genotype (OR=3.9, cP =0.003) were lower than controls. In thyroid-associated ophthalmopathy, the frequencies of GPR174 rs3810711 T allele (OR=7.9, cP =0.000), GRP174 rs3827440 T allele (OR=7.9, cP =0.000), ITM2A-GPR174 rs5912838 A allele (OR=3.1, cP =0.001) were increased and of GPR174 rs3810711 CC genotype (OR=0.1, cP =0.000), GRP174 rs3827440 CC genotype (OR=0.1, cP =0.000), ITM2A-GPR174 rs5912838 CC genotype (OR=0.3, cP =0.014)were lower than controls. Conclusions. Our results suggest that polymorphisms of GPR174 and ITM2A genes on X chromosome might contribute to the pathogenesis of AITD.

Thyroid lymphomas in human thyroid tissue with autoimmune thyroid disease xenografted in severe combined immunodeficient mice

1994 ◽  
Vol 5 (3) ◽  
pp. 169-177
Author(s):  
Tetsuya Morita ◽  
Norio Yoshikawa ◽  
Fumito Akasu ◽  
Sylvia L. Asa ◽  
Naomi Miller ◽  
...  
Keyword(s):  
Thyroid Disease ◽  
Autoimmune Thyroid Disease ◽  
Thyroid Tissue ◽  
Human Thyroid ◽  
Autoimmune Thyroid ◽  
Immunodeficient Mice ◽  
Human Thyroid Tissue

Besondere Manifestationsformen der Autoimmunthyreopathie

Praxis ◽  
2002 ◽  
Vol 91 (27) ◽  
pp. 1151-1160
Author(s):  
Fajfr ◽  
Müller
Keyword(s):  
Thyroid Disease ◽  
Autoimmune Thyroid Disease ◽  
Chromosome 6 ◽  
Autoimmune Thyroid

Les maladies thyroïdiennes auto-immunes ou immunes (autoimmune thyroid disease, AITD) sont relativement fréquentes. Le terme de AITD comprend les thyréodites euthyroidiennes ou hypothyroïdiennes de Hashimoto avec ou sans goitre, les hyperthyroïdies classiques de Basedow et leurs variantes nettement plus rares euthyroïdiennes ou hypothyroïdiennes. Aucune des nombreuses classifications des AITD n'a pu s'imposer sur le plan international. La pathogénèse de toutes les formes d'AITD comprend une perturbation de la tolérance immune chez les individus prédisposés génétiquement (séquence HLA-DQAI*0501 sur le bras court du chromosome 6) qui provoque un processus auto-immun contre la glande thyroïdienne. Ces processus sont soit destructeurs ou inhibiteurs, soit stimulateurs, ce qui permet d'expliquer les formes très différentes de AITD. Dans de cas rares, ces processus peuvent se contrebalancer («balance hypotheseis»). Les anticorps anti-récepteurs TPO et TSH (TRAK) ont une place particulière dans le diagnostic des AITD. Les dosages de routine utilisent pour la mesure des TRAK des récepteurs qui ne peuvent pas différencier entre les anticorps stimulants ou bloquants contre les récepteurs TSH. C'est, entre autre pour ces raisons, que les résultats d'anticorps positifs ne sont utilisables qu'en connaissance de la clinique et / ou des paramètres de la fonction thyroïdienne. Ce travail présente quatre patients avec des formes plus complexes d'AITD et résume les connaissances actuelles.

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