REGULATION OF EXPERIMENTAL AUTOIMMUNE THYROIDITIS: INFLUENCE OF NON‐<i>H‐2</i> GENES

Beisel, Kirk W.; Kong, Yi‐chi M.; Babu, KV Sreedhar; David, Chella S.; Rose, Noel R.

doi:10.1111/j.1744-313x.1982.tb00981.x

Cited by 32 publications

(13 citation statements)

References 29 publications

(25 reference statements)

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“…Susceptibility to EAT in mice was traditionally thought to be influenced only by the mouse class II MHC genes (39,56). However, further studies have shown that other genes outside the MHC gene complex must be involved in the susceptibility to EAT in mice (57,58). Moreover, one study (59) has shown that induction of EAT by immunization with Tg from different strains of mice had a profound effect on the degree of thyroiditis developed, suggesting that alterations in the sequence͞structure of mTg were important for the development of EAT.…”

Section: Discussionmentioning

confidence: 99%

Amino acid substitutions in the thyroglobulin gene are associated with susceptibility to human and murine autoimmune thyroid disease

Ban

Greenberg

Concepcion

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

174

131

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The 8q24 locus, which contains the thyroglobulin (Tg) gene, was previously shown to be strongly linked with autoimmune thyroid disease (AITD). We sequenced all 48 exons of the Tg gene and identified 14 single-nucleotide polymorphisms (SNPs). Case control association studies demonstrated that an exon 10 -12 SNP cluster and an exon 33 SNP were significantly associated with AITD (P < 0.01). Haplotype analysis demonstrated that the combination of these two SNP groups was more significantly associated with AITD (P < 0.001). Gene-gene interaction studies provided evidence for an interaction between HLA-DR3 and the exon 33 SNP, giving an odds ratio of 6.1 for Graves' disease. We then sequenced exons 10,12, and 33 of the mouse Tg gene in 19 strains of mice. Fifty percent of the strains susceptible to thyroiditis had a unique SNP haplotype at exons 10 and 12, whereas none of the mouse strains that were resistant to thyroiditis had this SNP haplotype (P ‫؍‬ 0.01). We concluded that Tg is a susceptibility gene for AITD, both in humans in and in mice. A combination of at least two Tg SNPs conferred susceptibility to human AITD. Moreover, the exon 33 SNP showed evidence for interaction with HLA-DR3 in conferring susceptibility to Graves' disease.Graves' disease ͉ Hashimoto's disease ͉ thyroiditis T he autoimmune thyroid diseases (AITDs), including Graves' disease (GD) and Hashimoto's thyroiditis (HT), are among the most common human autoimmune diseases with recent data showing a prevalence of clinical AITD of up to 1% in the U.S. population (1, 2). The hallmark of GD is the production of thyroid-stimulating hormone receptor (TSHR)-stimulating antibodies causing hyperthyroidism, whereas HT is characterized by the apoptosis of thyrocytes, leading to hypothyroidism (reviewed in refs. 3 and 4). However, despite their contrasting clinical presentations, GD and HT share many features in common, mainly, infiltration of the thyroid by T cells and production of antithyroid autoantibodies [antithyroglobulin and anti-thyroid peroxidase (TPO) antibodies] (3-5). AITDs are complex diseases, which are caused by an interaction between susceptibility genes (6-8) and nongenetic factors, such as infection (9-12). This paradigm is based on solid epidemiologic evidence demonstrating a genetic predisposition to AITDs, including: (i) familial clustering (13); (ii) a sibling risk ratio ( s ) of Ͼ10 (7, 14); (iii) a high concordance rate in monozygotic twins when compared with dizygotic twins (15-18); and (iv) the presence of thyroid autoantibodies, which are markers of subclinical AITD, in up to 50% of siblings of patients with AITD (19,20).We have previously performed a whole-genome scan in a dataset of 102 multiplex, multigenerational AITD families (540 individuals; refs. 21-23). Three loci on chromosomes 6p, 8q, and 10q showed evidence for linkage with the entire AITD dataset giving maximum multipoint heterogeneity logarithm of odds (lod) scores of 2.0, 3.5, and 4.1, respectively. The 8q24 locus was also reported to be linked with AITD in a dat...

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Section: Discussionmentioning

confidence: 99%

Amino acid substitutions in the thyroglobulin gene are associated with susceptibility to human and murine autoimmune thyroid disease

Ban

Greenberg

Concepcion

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

174

131

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“…In the mouse model of experimental autoimmune thyroiditis (EAT), induced by thyroglobulin, genes within and without the major histocompatibility complex (MHC) locus have been implicated in the regulation of the disease process (Kuppers et al 1988 a;Vladutiu and Rose, 1971;Tomazic et al 1974;Ben-Nun et al, 1980;Beisel et al 1982aBeisel et al , 1982b. Genetic loci outside the MHC locus that influence EAT have not been mapped.…”

Section: Introductionmentioning

confidence: 99%

The IgG2a antibody response to thyroglobulin is linked to the Igh locus in mouse

et al. 1994

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The IgG-subclass usage by several strains of mice in the response to immunization with mouse thyroglobulin (mTg) was examined in the experimental autoimmune thyroiditis model. While the subclass usage by most mouse strains was similar, the Ighb allotype-bearing mice consistently produced lower IgG2a levels to mTg. Using CBA-Ighb congenic and recombinant inbred strains of mice, the lower level of IgG2a in the Ighb mouse was mapped to the Igh locus. The regulation of IgG2a appeared to be cis controlled, as the CBA x C57BL/6F1 mouse also produced reduced IgG2a of the Ighb (B6) allotype but not of the Ighj (CBA) allotype.

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“…Further studies on Tg-mediated EAT localized control of susceptibility in the H-2A region of the H-2k haplotype (Beisel et al 1982a). Genetic influences on EAT development have also been attributed to the K or the D region of the H-2 complex (Maron and Cohen 1979;Ben-Nun et al 1980;Maron and Cohen 1980;Kong et al 1979) and to non-H-2 genes (Beisel et al 1982b). …”

mentioning

confidence: 99%

H-2Ek expression influences thyroiditis induction by the thyroglobulin peptide (2495-2511)

Chronopoulou

Carayanniotis

1993

Immunogenetics

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REGULATION OF EXPERIMENTAL AUTOIMMUNE THYROIDITIS: INFLUENCE OF NON‐H‐2 GENES

Cited by 32 publications

References 29 publications

Amino acid substitutions in the thyroglobulin gene are associated with susceptibility to human and murine autoimmune thyroid disease

Amino acid substitutions in the thyroglobulin gene are associated with susceptibility to human and murine autoimmune thyroid disease

The IgG2a antibody response to thyroglobulin is linked to the Igh locus in mouse

H-2Ek expression influences thyroiditis induction by the thyroglobulin peptide (2495-2511)

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