Genetic studies have identified the HLA and CTLA4 regions as susceptibility loci for the development of common autoimmune thyroid diseases (AITDs), including Graves' disease and autoimmune hypothyroidism.
Here we identify polymorphisms of the cytotoxic T lymphocyte antigen 4 gene (CTLA4)--which encodes a vital negative regulatory molecule of the immune system--as candidates for primary determinants of risk of the common autoimmune disorders Graves' disease, autoimmune hypothyroidism and type 1 diabetes.
The aim of this study was to determine whether allelic association was present between the A-G single nucleotide polymorphism (SNP) at position 49 in exon 1 of the CTLA-4 gene and autoimmune hypothyroidism.
Recent studies have demonstrated an association of a microsatellite polymorphism [variant lengths of a dinucleotide (AT)n repeat] lying in exon 3 of the CTLA-4 gene, specifically a 106-bp allele, with autoimmune disorders, such as Graves' disease, autoimmune Addison's disease and autoimmune hypothyroidism.
Recent studies have demonstrated an association between a microsatellite polymorphism of the CTLA-4 gene, specifically a 106 base pair allele, and both Graves' disease and autoimmune hypothyroidism.
These results confirm that the CTLA-4 gene, or one closely associated with it, confers susceptibility to Grave's disease but is not specific as the CTLA-4 106 allele is also associated with autoimmune hypothyroidism.
A cross-sectional study was performed in 278 patients (140 patients treated for differentiated thyroid carcinoma (DTC) and 138 with autoimmune hypothyroidism (AIH)) genotyped for the TSHR-Asp727Glu polymorphism.
In Graves' disease, antibodies directed against the thyrotropin receptor (TSH-R) lead to the development of glandular overactivity, while in autoimmune hypothyroidism, cell-mediated and humoral thyroid injury leads to destruction of thyroid tissue and thyroid hormone deficiency.
We investigated whether the associations between HLA alleles of patients with autoimmune hypothyroidism varied according to the presence or absence of TSH receptor-blocking antibody (TRBab).
Our results suggest +49A/G and CT60 polymorphism of CTLA4 and E33 polymorphism of TG may be genetic risk factors for autoimmune hypothyroidism susceptibility and down regulation of both forms of CTLA4 advocates the crucial role of CTLA4 in pathogenesis of autoimmune hypothyroidism.
Individuals with positive thyroid peroxidase antibodies (TPOAbs) have an increased risk of autoimmune hypothyroidism (Hashimoto's thyroiditis), as well as autoimmune hyperthyroidism (Graves' disease).
It was concluded that: TS patients are at higher than average risk of developing AITD not only in adolescence and adult age but also in childhood; hypothyroidism, mainly subclinical, is the most frequent thyroid dysfunction; elevated TPO-ab and/or TG-ab alone do not imply thyroid dysfunction; TS-ab or TSHB-ab are always associated with thyroid dysfunction although most cases of autoimmune hypothyroidism are not due to the latter antibody.
It was concluded that: TS patients are at higher than average risk of developing AITD not only in adolescence and adult age but also in childhood; hypothyroidism, mainly subclinical, is the most frequent thyroid dysfunction; elevated TPO-ab and/or TG-ab alone do not imply thyroid dysfunction; TS-ab or TSHB-ab are always associated with thyroid dysfunction although most cases of autoimmune hypothyroidism are not due to the latter antibody.
Our results suggest +49A/G and CT60 polymorphism of CTLA4 and E33 polymorphism of TG may be genetic risk factors for autoimmune hypothyroidism susceptibility and down regulation of both forms of CTLA4 advocates the crucial role of CTLA4 in pathogenesis of autoimmune hypothyroidism.
In summary, we report that oncocytes are the result of an increased immunoproteasome expression secondary to a chronic inflammatory milieu, and suggest LMP2 as a novel therapeutic target for the treatment of oncocytic lesions and autoimmune hypothyroidism.
Autoimmune thyroid diseases (AITDs) including Graves disease (GD) and autoimmune hypothyroidism (AH) are associated with TNF genes polymorphisms.TNF molecules bind to TNFRI and TNFRII.
The authors previously reported the results of a clinical trial in which some patients with metastatic prostate cancer treated with flt3 ligand developed autoimmune hypothyroidism with thyroid-specific antibodies.
Graves' disease (GD) is associated with the histocompatibility leucocyte antigen (HLA) haplotype A*01-B*0801-DRB1*0301-DQA1*0501-DQB1*0201 (or B8/DR3) whereas autoimmune hypothyroidism (AIH) has been weakly associated with HLA DRB1*03, *04 and *11/*12 alleles (or DR3, DR4 and DR5).
Graves' disease (GD) is associated with the histocompatibility leucocyte antigen (HLA) haplotype A*01-B*0801-DRB1*0301-DQA1*0501-DQB1*0201 (or B8/DR3) whereas autoimmune hypothyroidism (AIH) has been weakly associated with HLA DRB1*03, *04 and *11/*12 alleles (or DR3, DR4 and DR5).
Graves' disease (GD) is associated with the histocompatibility leucocyte antigen (HLA) haplotype A*01-B*0801-DRB1*0301-DQA1*0501-DQB1*0201 (or B8/DR3) whereas autoimmune hypothyroidism (AIH) has been weakly associated with HLA DRB1*03, *04 and *11/*12 alleles (or DR3, DR4 and DR5).
Analysis showed a reduced frequency of the variant t allele in the IL-4 promoter polymorphism (position 590) in patients with GD and in the entire patient group (GD and AIH) compared with the control group [corrected P (Pc) = 0.00004 and Pc < 0.00001 for GD and all patients, respectively].
All three patients positive for Pmel17 antibodies (aged 50-63 years) had had vitiligo of the symmetrical type for > 1 year and all of them also had an associated autoimmune disorder: GD in one and autoimmune hypothyroidism in two.