Novel Insights Into Tissue-Specific Biochemical Alterations in Pediatric Eosinophilic Esophagitis Using Raman Spectroscopy

INTRODUCTION: Elucidating esophageal biochemical composition in eosinophilic esophagitis (EoE) can offer novel insights into its pathogenesis, which remains unclear. Using Raman spectroscopy, we profiled and compared the biochemical composition of esophageal samples obtained from children with active (aEoE) and inactive EoE (iEoE) with non-EoE controls, examined the relationship between spectral markers and validated EoE activity indices. METHODS: In vitro Raman spectra from children with aEoE (n = 8; spectra = 51) and iEoE (n = 6; spectra = 48) and from non-EoE controls (n = 10; spectra = 75) were acquired. Mann-Whitney test was used to assess the differences in their Raman intensities (median [interquartile range]) and identify spectral markers. Spearman correlation was used to evaluate the relationship between spectral markers and endoscopic and histologic activity indices. RESULTS: Raman peaks attributable to glycogen content (936/1,449 cm(−1)) was lower in children with aEoE (0.20 [0.18–0.21]) compared with that in non-EoE controls (0.24 [0.23–0.29]). Raman intensity of proteins (1,660/1,209 cm(−1)) was higher in children with aEoE compared with that in non-EoE controls (3.20 [3.07–3.50] vs 2.91 [2.59–3.05]; P = 0.01), whereas that of lipids (1,301/1,260 cm(−1)) was higher in children with iEoE (1.56 [1.49–1.63]) compared with children with aEoE (1.40 [1.30–1.48]; P = 0.02). Raman peaks attributable to glycogen and lipid inversely correlated with eosinophilic inflammation and basal zone hyperplasia. Raman mapping substantiated our findings. DISCUSSION: This is the first study to identify spectral traits of the esophageal samples related to EoE activity and tissue pathology and to profile tissue-level biochemical composition associated with pediatric EoE. Future research to determine the role of these biochemical alterations in development and clinical course of EoE can advance our understanding of EoE pathobiology.