Clinicopathologic and gene expression analysis of initial biopsies from patients with eosinophilic esophagitis refractory to therapy
HUMAN PATHOLOGY
Authors: Siddique, Ayesha S.; Corney, David C.; Mangray, Shamlal; Lombardo, Kara A.; Chen, Sonja; Marwaha, Alexander S.; Resnick, Murray B.; Herzlinger, Michael; Matoso, Andres
Abstract
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 6 months 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 presenting symptoms among groups. The number of eosinophils/high-power field among nonresponders 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 with reflux at a false discovery rate < 0.05, including overexpression of ALOXI 5, CCL26, FCER2, RTNLB, and RNASE2, and underexpression of DSG1. EoE patients refractory to therapy or who relapsed showed a trend toward higher ALOXI 5 expression compared with 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 versus 3-fold; P < .01). In conclusion, the number of eosinophils/high-power field in the initial biopsy inversely correlates with therapy response. Overexpression of RTNLB in refractory-to-therapy patients and overexpression of ALOXI.5 and CCL26 suggest that they are critical in the EoE pathogenesis. (C) 2017 Elsevier Inc. All rights reserved.
Asthma-related SNP in FCER2 is associated with increased expression of IL-4R on human B cells
INTERNATIONAL JOURNAL OF IMMUNOGENETICS
Authors: Chan, M. A.; Gigliotti, N. M.; Meng, J.; Rosenwasser, L. J.
Abstract
A SNP (rs2228137) (R62W) in FCER2 has been linked with severe exacerbations in asthmatics. Transfectants expressing the SNP exhibited increased IL-4Ra expression after stimulation through CD23 compared with wild-type. Our data suggest that the SNP may favour increased IgE production through increased responsiveness to IL-4 in patients possessing this genotype.