Interactions between cytokines and others soluble factors (hormones, antibodies. . .) can play an important role in the development of thyroid pathogenesis.The purpose of the present study was to examine the possible correlation between serum cytokine concentrations, thyroid hormones (FT4 and TSH) and auto-antibodies (Tg and TPO), and their usefulness in discriminating between different thyroid conditions. In this study, we investigated serum from 115 patients affected with a variety of thyroid conditions (44 Graves' disease, 17 Hashimoto's thyroiditis, 11 atrophic thyroiditis, 28 thyroid nodular goitre and 15 papillary thyroid cancer), and 30 controls. Levels of 17 cytokines in serum samples were measured simultaneously using a multiplexed human cytokine assay. Thyroid hormones and auto-antibodies were measured using ELISA. Our study showed that IL-1 serum concentrations allow the discrimination between atrophic thyroiditis and papillary thyroid cancer groups (p = 0.027).
Autoimmune thyroid diseases (AITDs), including Graves' disease (GD) and Hashimoto thyroiditis, are associated with human MHC polymorphisms. The present study analysed two polymorphisms within tumour necrosis factor (TNF) genes (TNF-308 A/G SNP and TNFb (CT)n microsatellite) in a sample of 106 GD patients and 199 controls from the Tunisian population. The present study was designed to investigate genetic association of these polymorphisms (taken separately or considered as a haplotype) with GD development. Statistical analysis confirmed the association between the TNF-308 A allele and GD (p = 0.002), previously reported in a Tunisian familial study. The data from the present study suggest that the TNF-308 A allele plays a role in GD pathogenesis in the Tunisian population. This association was further confirmed by a meta-analysis on eight published studies (p < 0.0001). Haplotype analysis with GD revealed an associated haplotype (TNFb3-TNF-308 G haplotype: chi2 = 13.16; p = 0.0003).
Autoimmune thyroid diseases (AITD), which include Hashimoto thyroiditis (HT), Graves' disease (GD) and primary idiopathic myxoedema (PIM), are recognized by their clinical and genetic heterogeneity. In this study, we have carried on a global approach gathering 20 year genetic and clinical data on a Tunisian multigenerational family (Akr). Our purpose was search for a combined genotype involved in AITD susceptibility using 33 gene polymorphisms. The Akr pedigree is composed of more than 400 members distributed on 10 generations. Clinical follow-up was performed by appreciation of the thyroid gland and measurement of both thyroid hormone and auto antibody levels. We used FBAT software to test for association between gene polymorphisms and AITDs. Clinical follow-up has showed that the number of AITD patients has increased from 25 to 78 subjects subdivided on 51 cases of GD, 22 PIM and 5 HT. Concerning genetic analysis, our study has revealed new gene association when compared with our previous analysis (considering single genes). Thus, PTPN22, TG and VDR gene polymorphisms have became associated with p-values ranging from 4.6 10− 2 to 4 10− 3 when considered with other genes on the same chromosome; giving evidence for gene interaction. The most significant association was found with the MHC region (p = 7.15 10− 4). Moreover, and among gene polymorphisms explored, our analysis has identified some of them as AITD biomarkers. Indeed, PDS gene polymorphisms were associated with either exophthalmia or goiter (p-values from 10− 2 to 10− 3). In conclusion, our study gives evidence for gene interaction in AITD development confirming genetic complexity of these diseases.
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