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Eosinophilic esophagitis (EoE) is often misdiagnosed as GERD; therefore, the goal of the current study is to establish a non-invasive diagnostic and monitoring biomarker that differentiated GERD from EoE. Reports indicates that IL-15 responsive iNKT cells and tissue specific IgE have a critical in EoE pathogenesis, not in GERD. Therefore, we tested the hypothesis that the panel of IL-15-responsive T cell and IgE receptors may be novel non-invasive biomarkers for EoE. Accordingly, the receptors of IL-15 responsive T cells (Vα24, Jα18, γδT, αβT) and IgE (FcεRI & FcεRII) were examined. The data indicates that blood mRNA levels of Vα24, Jα18, γδ T, αβ T and FcεRI are significantly reduced in EoE compared to the GERD patients and normal individuals. The ROC curve analysis indicated FcεRII, Jα18 and δ TCR are the positive predictors that discriminate EoE from GERD. Thus, these molecules will be a novel non-invasive diagnostic biomarker for EoE. • Decreased blood IL-15Rα mRNA levels differentiate EoE and GERD patient.. • Decreased blood mRNA levels of IL-15 responsive γδ T cells receptors differentiate EoE and GERD patient. • Decreased blood mRNA levels of IL-15 responsive iNKT cell receptors and IgE receptors differentiate EoE and GERD patient. • The levels of blood T cell receptors mRNA in EoE & GERD with perfect ROC curves establishes non-invasive biomarker for EoE. [ABSTRACT FROM AUTHOR]