Clinicopathologic and gene expression analysis of initial biopsies from patients with eosinophilic esophagitis refractory to therapy

Publication date: Available online 4 September 2017
Source:Human Pathology
Author(s): Ayesha S. Siddique, David C. Corney, Shamlal Mangray, Kara A. Lombardo, Sonja Chen, Alexander S. Marwaha, Murray B. Resnick, Michael Herzlinger, Andres Matoso
Some patients with eosinophilic esophagitis (EoE) do not respond to therapy. The clinicopathologic characteristics, and gene expression profile at time of presentation could help predict response to therapy. Refractory EoE was defined as persistence of symptoms and biopsies with histologic features of EoE after 6months of therapy with proton pump inhibitors and topical corticosteroids. Initial biopsies from refractory EoE patients (n=21), responder to therapy (n=8), patients who relapsed (n=6), and reflux controls (n=24) were studied. RNA was isolated from a subset of cases and gene expression analysis of 285 genes involved in inflammation was performed using NanoString technology. There was no difference in the presentating symptoms among groups. The number of eosinophils/HPF amongst non-responders was higher (66±15) than responders (39±8; P<.0001) and similar to patients who relapsed (62±11). Six genes were expressed by at least 4-fold compared to reflux at a false discovery rate (FDR)<0.05, including overexpression of ALOX15, CCL26 and FCER2, RTNLB, and RNASE2, and underexpression of DSG1. EoE patients refractory to therapy or who relapsed showed a trend towards higher ALOX15 expression compared to patients with good response to therapy (364.4 and 425 fold change, P=.097 and P=.07). RTNLB was significantly overexpressed in patients who were refractory to therapy versus those who responded favorably (10-fold vs. 3-fold; P<.01). In conclusion, the number of eosinophils/HPF in the initial biopsy inversely correlates with therapy response. Overexpression of RTNLB in refractory to therapy patients and overexpression of ALOX15 and CCL26 suggest they are critical in the EoE pathogenesis.



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