Transcriptome analysis of thyroid tissue in patients with Hashimoto’s disease using next-generation sequencing: case–control study

Aim: Hashimoto’s thyroiditis (HT) is a common but poorly understood autoimmune disease. Here, we aimed to identify differentially expressed genes and biological signaling pathways associated with HT by comparing whole genome transcriptomes from affected and healthy donors. Methods: As part of a case–control design, we analyzed thyroid tissue RNA sequencing libraries from the Genotype-Tissue Expression Project (v8 release). Donors were divided into two demographically and technically matched groups according to the presence (n = 31) or absence of histopathologically confirmed HT in their thyroid tissue samples (n = 73). Differential gene expression analysis was performed, followed by pathway enrichment profiling (Hallmark, Kyoto Encyclopedia of Genes and Genomes). Results: In total, we identified 2,809 upregulated genes and 2,348 downregulated genes (fold change > 1.5, Benjamini-Hochberg adjusted P < 0.05). HT was characterized by pathways associated with T- and B-cell signaling, antigen processing, cytokine-cytokine receptor interactions, phagocytic responses, and cell death. The transition to HT was accompanied by a decreased expression of gene sets related to cell junctions, cell polarity, epithelial and anabolic processes, redox homeostasis, mitochondrial health, and Hippo signaling. Loss of endothelial cell characteristics and positional markers of perivascular fibroblasts followed closely thereafter. Conclusions: The local expansion of cellular, humoral and innate immunity is a hallmark of HT. Cell death dominated the scene, followed by signs of epithelial, endothelial and stromal remodeling of thyroid tissue. This included reciprocal contraction of the terminally differentiated epithelium and (perivascular) endothelium amidst increasing autoimmune activity. Widespread changes in gene activity were observed in various homeostatic processes, including cell metabolism, cellular energetics, and anabolic and catabolic metabolic pathways.