ArticleClinical and translational gastroenterology2026
Replication of Endotypes in Eosinophilic Esophagitis Using a Curated Gene Panel Compared to Bulk Sequencing and Assessing Stability Over Time.
Article in Clinical and translational gastroenterology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
introductionIt is unknown whether eosinophilic esophagitis (EoE) endotypes can be replicated using whole transcriptome data or if endotypes persist after treatment. We investigated endotypes with a curated gene panel and bulk sequencing and assessed endotype stability after topical steroid (tCS) treatment.
methodsWe analyzed specimens collected during a randomized trial of tCS for newly diagnosed EoE. Bulk RNA-seq was performed on pretreatment and post-treatment esophageal biopsies. For pretreatment samples, we used the EoE diagnostic panel (EDP) to assess previously described endotypes. We then identified endotypes using consensus clustering from the top 1,500 most variable genes from bulk sequencing. This process was repeated for post-treatment samples, and pretreatment/post-treatment comparisons were made. Clinical characteristics were assessed by endotype.
resultsWe replicated the 3 previously reported EDP EoE endotypes. EoEe1 was mild and treatment responsive compared with e2 and e3 (95% histologic response [<15 eos/hpf] vs 59% and 59%; P = 0.01), whereas e2/e3 had more severe endoscopic findings. Two endotypes predominated in bulk sequencing data. Compared with cluster 1, cluster 2 trended to more histologic response (76% vs 59%; P = 0.08) and endoscopic findings were milder. After treatment, endotypes did not persist; gene expression was dependent on histologic response. DISCUSSION: We replicated the 3 EDP-based endotypes in newly diagnosed patients with EoE, although clinical correlations were not as strong as previously reported. Using bulk sequencing data, 2 endotypes were noted. Post-treatment gene expression changes after tCS therapy suggest that endotype is best assessed at diagnosis and before treatment.
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