mRNA-Seq reveals novel molecular mechanisms and a robust fingerprint in Graves' disease
| Autor: | Rauf Latif, Xiaoming Yin, Terry F. Davies, Ravi Sachidanandam, Syed A. Morshed, Ruijin Shi |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
medicine.medical_specialty
Pathology Endocrinology Diabetes and Metabolism Graves' disease medicine.medical_treatment Clinical Biochemistry Thyroid Gland Context (language use) Human leukocyte antigen Tissue Banks Biology Biochemistry Transcriptome Endocrinology Internal medicine medicine Humans RNA Messenger Thyroid Epithelial Cells JCEM Online: Advances in Genetics Sequence Analysis RNA Histocompatibility Testing Biochemistry (medical) Thyroid Thyroidectomy medicine.disease Graves Disease medicine.anatomical_structure Cytokines PAX8 Signal Transduction |
| Zdroj: | The Journal of clinical endocrinology and metabolism. 99(10) |
| ISSN: | 1945-7197 |
| Popis: | Context: The immune response in autoimmune thyroid disease has been shown to occur primarily within the thyroid gland in which the most abundant antigens can be found. A variety of capture molecules are known to be expressed by thyroid epithelial cells and serve to attract and help retain an intrathyroidal immune infiltrate. Objective: To explore the entire repertoire of expressed genes in human thyroid tissue, we have deep sequenced the transcriptome (referred to as mRNA-Seq). Design and Patients: We applied mRNA-Seq to thyroid tissue from nine patients with Graves' disease subjected to total thyroidectomy and compared the data with 12 samples of normal thyroid tissue obtained from patients having a thyroid nodule removed. The expression for each gene was calculated from the sequencing data by taking the median of the coverage across the length of the gene. The expression levels were quantile normalized and a gene signature was derived from these. Results: On comparison of expression levels in tissues derived from Graves' patients and controls, there was clear evidence for overexpression of the antigen presentation pathway consisting of HLA and associated genes. We also found a robust disease signature and discovered active innate and adaptive immune signaling networks. Conclusions: These data reveal an active immune defense system in Graves' disease, which involves novel molecular mechanisms in its pathogenesis and development. |
| Databáze: | OpenAIRE |
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