الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Hashimoto’s thyroiditis (HT) is part of a spectrum of thyroid autoimmune conditions, the pathogenesis is still not fully understood but it’s mostly interaction of environmental factors with genetic susceptibility associated with immunological dysregulation.
Both cellular and humoral immunity play a role in HT pathogenesis. Defects in T regulatory cells and increased activation of follicular helper T cells may have a role in disease initiation. Infiltrating lymphocytes can be directly cytotoxic to thyroid follicular cells (TFC) or may affect cell viability/function indirectly through cytokine production, which alters TFC integrity and modulates their metabolic and immune function. Thyroid peroxidase and thyroglobulin antibodies are present in the majority of HT patients. Recent work has identified DNA frag, generated following cell death, and micro RNA as potential factors in HT pathogenesis.
MicroRNAs are a series of small noncoding RNAs. They constitute about three percent of the whole genome. About ninety percent genes could be regulated by microRNAs. They could regulate the target genes through binding to the target genes’ 3 0 -UTR. They play important roles in the cell proliferation, apoptosis and other biological processes
MiR-375 was first identified as a pancreatic islet-specific miRNA regulating insulin secretion. However, further study revealed that miR-375 is a multifunctional miRNA participating in pancreatic islet development, glucose homeostasis, mucosal immunity, lung surfactant secretion and tumorogenesis.
However, very limited studies are available for role of microRNAs in HT. The aim of this study was to assess the role of miRNA-375 in pathogenesis of Hashimoto’s thyroiditis and to clarify this, relative expression of microRNA-375 was assessed in 35 female Hashimoto’s thyroiditis patients (group I) in comparison to 15 healthy female subjects (group II).
The results showed that relative quantification of plasma microRNA-375 expression level in our study ranged from 0.7 to 35 in Hashimoto’s thyroiditis patients (group I) with a mean value (5.0 ± 7.52) while in healthy subjects (group II) ranged from 0.3 to 2.2 with a mean value (1.17 ± 0.61). The relative expression of microRNA-375 was higher in group I versus group II.
Also, microRNA-375 relative expression and level of TSH was found to be positively correlated to relative expression of microRNA-375, while miRNA expression was inversely correlated with T3 and T4 although, it didn’t reach a statistical significance with T4 and these results link microRNA-375 and hypothyroidism frequently found in HT cases.
A statistical significant positive correlation was found between expression levels of miRNA -375 and anti-TPO Abs.
Several studies investigate the role of microRNA-375 in the different types of cancers including DTC. In our study a total of 11 nodules in 9 patients with Hashimoto’s thyroiditis (group I) were detected. 9/ 11 nodules were eligible for FNAC according to the ultrasound characteristics of thyroid nodules & estimated malignancy risk as proposed by ATA guidelines. (261) 1 case was non-diagnostic and refused to repeat FNAC, 2 cases were benign, 1 case was reported as atypia of unknown significance ,3 cases were reported as follicular neoplasms and 2 cases were suspicious for malignancy according to the Bethesda cytopathological classification of thyroid nodules. (262) 6 cases were sent to surgery, where the gross pathology of the submitted specimens showed 1 cases with hyperplastic nodule, 2 cases consistent with PTC and 3 cases with follicular thyroid carcinoma.
We studied the relative expression of microRNA-375 in Hashimoto’s thyroiditis patients , patients with nodules (proved DTC) and healthy subjects and the mean of relative microRNA-375 expression was (5.96 ± 8.53), (2.22 ± 0.97) and (1.17 ± 0.61) respectively.