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Masaki Asakage, Yoshihiko Usui, Marina Ogawa, Naoyuki Yamakawa, Kazuhiko Umazume, Rei Nemoto, Hiroshi Goto, Naoya Nezu, Masahiko Kuroda; Comprehensive genetic analysis of IgG4-related ophthalmic diseases by RNA sequencing. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3434.
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© ARVO (1962-2015); The Authors (2016-present)
High-throughput RNA sequencing (RNA-Seq) uses massively parallel sequencing that allows unbiased analysis of both genome-wide transcription levels and mutation status of tumors. Immunoglobulin G4-related ophthalmic disease (IgG4-ROD) is a fibroinflammatory disease characterized by enlargement of ocular adnexal tissues, infiltration of IgG4-positive plasmacytes, and elevated serum IgG4 levels. Comprehensive analysis of gene abnormalities in IgG4-ROD may play an important role in discovering new biomarkers and establishing treatments. However, strategy for analysis is still in the development stage. In this study, we analyzed RNA expression levels in biopsy specimens of IgG4-ROD.
This study included 3 patients who were diagnosed with IgG4-ROD at Tokyo Medical University Hospital. Total RNA was extracted from specimens obtained by biopsy and per-tumor adipose tissues as control, and quantified using NextSeq 500 (Illumina). CLC Genomics Workbench was used to analyze the data.
By comparing RNA expression levels in the biopsy specimens with those in control tissues and extracting genes with an expression ratio of 16 or more and an expression difference of 16 or more, expression differences were observed in 221 genes. Pathway analysis with these genes revealed a difference in pathways related to immune systems, extracellular matrix organization, signal transduction, hemostasis, metabolism, vesicle-mediate transport, cellular responses to external stimuli, disease, developmental biology, metabolism of proteins, gene expression (transcription), transport of small molecules, neuronal system, metabolism of RNA, and muscle contraction. Among them we identified seven known and novel candidate genes that were associated with IgG4-ROD.
In biopsy specimens of IgG4-ROD, we identified novel gene abnormalities that are associated with extracellular matrix degradation, B cell receptor signaling pathways, receptor of Epsterin-Barr virus, immunoglobulin, B cell development, and many cellular processes. These data may contribute to future development of new biomarkers for diagnosis and molecular-targeted drugs to treat this refractory disease.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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