MRNA-Seq reveals novel molecular mechanisms and a robust fingerprint in Graves' disease

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 beexpressedby thyroid epithelial cells and servetoattract 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 with12 samples of normal thyroid tissue obtained from patients having a thyroid nodule removed. The expression for each gene was calculated from the sequencing databy taking the median of the coverage across the lengthof the gene.The expressionlevels 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 anactive immune defense system in Graves' disease, which involves novel molecular mechanisms in its pathogenesis and development.