Subtyping Idiopathic Uveitis by Gene Expression
By Lynda Seminara
Selected By: Richard K. Parrish II, MD
Journal Highlights
American Journal of Ophthalmology, February 2021
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Rosenbaum et al. set out to test the hypothesis that idiopathic uveitis may have subtypes, based on gene expression. They found that gene expression profiling was 85% accurate when uveitis was associated with one of four systemic diseases.
The authors used RNA sequencing to characterize the gene expression profile in peripheral blood collected from patients with uveitis associated with axial spondyloarthritis (n = 17), sarcoidosis (n = 13), inflammatory bowel disease (n = 12), or tubulointerstitial nephritis (n = 10). They also determined gene expression levels for 18 healthy control subjects.
In addition, peripheral blood gene expression was characterized for 38 patients with idiopathic uveitis to determine if a likely diagnosis could be established from the transcriptional signature. A high-dimensional negative binomial regression model was used to compare each disease group with the control subjects, and the 20 most distinctive genes for each diagnosis were extracted. All told, 80 genes were extracted; of these, 75 were found to be unique. From these unique genes, the authors devised a classification algorithm by fitting a gradient boosting tree with fivefold cross-validation. They assessed the algorithm’s utility by calculating diagnostic probability for each case of idiopathic uveitis.
Overall, gene expression profiling was 85% accurate when the uveitis was ascribed to one of the four diseases. Although many patients with idiopathic uveitis may not have one of these systemic diseases, the gene expression profile helped determine the probable diagnosis in 11 of the 38 idiopathic cases (29%).
The original article can be found here.