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Altered expression of CTLA4, CD28, VDR and CD45 mRNA in T-cells of patients with Hashimoto's thyroiditis - a pilot study

Introduction: CD28/T-cell receptor (TCR)/cytotoxic T-lymphocyte antigen 4 (CTLA4) complex controls T-cell tolerance and autoimmunity in Hashimoto’s thyroiditis (HT). In addition, CD45 protein tyrosine phosphatase (PTPase) and vitamin D receptor (VDR) cooperatively interact with the TCR complex to affect autoimmune processes central to the pathogenesis of HT. Nevertheless, their role in HT aetiology has been less well established. In this study, we aimed to explore mRNA expression levels of CTLA4, CD28, CD45 and VDR in T-cells, across different outcomes of HT. Material and methods: The study included 45 HT patients and 13 euthyroid, healthy controls. T-lymphocytes were isolated from peripheral blood mononuclear cells, total mRNA was extracted from T-cells and gene expression was studied by reverse transcription- polymerase chain reaction (RT-PCR) and ImageQuant method relative to glyceraldehyde-3-phosphate dehydrogenase RT-PCR products. Results: A nominally higher expression level of VDR, CTLA4, CD28 and CD45RAB mRNA was found in unsorted T- lymphocytes of healthy controls when compared to the HT patients. No difference was observed between hypothyroid/untreated, spontaneously euthyroid and LT4-treated HT patients. VDR mRNA expression was linked to both T3 levels and CTLA4 gene expression, whilst CD45RB mRNA expression coincided with CTLA4 and CD28 transcript levels. Conversely, older age and lower T3 levels were associated with increased abundance of CD45R0 isoform in HT patients. Conclusions: The results suggest a cross talk between endocrine and immune functions in HT pathology: an altered peripheral T cell mRNA profile with reduced VDR, CTLA4, CD28 and CD45RAB transcript levels is accompanied by age-related shift from naive to memory/late- differentiated T cell CD45R mRNA signature and associated with thyroid hormone status in the HT patients.

Hashimoto disease ; CD4 positive T lymphocytes ; vitamin D3 receptor ; CD28 antigen ; cytotoxic T-lymphocyte-associated antigen 4 ; CD45 antigen

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