Details

Autor(en) / Beteiligte

• Rosenbaum, James T.
• Harrington, Christina A.
• Searles, Robert P.
• Fei, Suzanne S.
• Zaki, Amr
• Arepalli, Sruthi
• Paley, Michael A.
• Hassman, Lynn M.
• Vitale, Albert T.
• Conrady, Christopher D.
• Keath, Puthyda
• Mitchell, Claire
• Watson, Lindsey
• Planck, Stephen R.
• Martin, Tammy M.
• Choi, Dongseok

Titel

Identifying RNA Biomarkers and Molecular Pathways Involved in Multiple Subtypes of Uveitis

Ist Teil von

• American journal of ophthalmology, 2021-06, Vol.226, p.226-234

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2021

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• •Uveitis is a heterogeneous collection of diseases.•Despite the heterogeneity of uveitis, specific RNA transcripts expressed by cells in peripheral blood as well as pathways involving multiple genes are common to different forms of uveitis.•The shared expression of mRNA from different forms of uveitis is consistent with a prior publication based on peripheral blood and thus independently validated.•Transcripts that are implicated in multiple forms of uveitis could suggest therapeutic targets that could benefit multiple forms of uveitis. Uveitis is a heterogeneous collection of diseases. We tested the hypothesis that despite the diversity of uveitides, there could be common mechanisms shared by multiple subtypes, and that evidence of these common mechanisms may be detected as gene expression profiles in whole blood. Cohort study. Ninety subjects with uveitis including axial spondyloarthritis (n = 17), sarcoidosis (n = 13), inflammatory bowel disease (n = 12), tubulointerstitial nephritis with uveitis (n = 10), or idiopathic uveitis (n = 38) as well as 18 healthy controls were enrolled, predominantly at Oregon Health & Science University. RNA-Seq data generated from peripheral, whole blood identified 19,859 unique transcripts. We analyzed gene expression pathways via Kyoto Encyclopedia of Genes and Genomes and Gene Ontology (GO). We validated our list of upregulated genes by comparison to a previously published study on peripheral blood gene expression among 50 subjects with diverse forms of uveitis. Both the Kyoto Encyclopedia of Genes and Genomes and GO analysis identified multiple shared pathways or GO terms with a P value of <.0001. Almost all pathways related to the immune response and/or response to an infection. A total of 119 individual transcripts were upregulated by at least 1.5-fold and false discovery rate <.05, and 61 were downregulated by similar criteria. Comparing mRNA from our study with a false discovery rate <.05 and the prior report, we identified 10 common gene transcripts: ICAM1, IL15RA, IL15, IRF1, IL10RB, GSK3A, TYK2, MEF2A, MEF2B, and MEF2D. Many forms of uveitis share overlapping mechanisms. These data support the concept that a single therapeutic approach could benefit diverse forms of this disease.