Noninvasive biomarkers identify eosinophilic esophagitis: A prospective longitudinal study in children

Abstract

Background Esophageal histology is critical for diagnosis and surveillance of disease activity in eosinophilic esophagitis (EoE). A validated noninvasive biomarker has not been identified. We aimed to determine the utility of blood and urine eosinophil‐associated proteins to diagnose EoE and predict esophageal eosinophilia. Methods Blood and urine were collected from children undergoing endoscopy with biopsy. Absolute eosinophil count (AEC), plasma eosinophil‐derived neurotoxin (EDN), eosinophil cationic protein (ECP), major basic protein‐1 (MBP‐1), galectin‐10 (CLC/GAL‐10), Eotaxin‐2 and Eotaxin‐3, and urine osteopontin (OPN) and matrix metalloproteinase‐9 (MMP‐9) were determined. Differences were assessed between EoE and control, and with treatment response. The capacity to predict EoE diagnosis and esophageal eosinophil counts was assessed. Results Of 183 specimens were collected from 56 EoE patients and 15 non‐EoE controls with symptoms of esophageal dysfunction; 33 EoE patients had paired pre‐ and post‐treatment specimens. Plasma (CLC/GAL‐10, ECP, EDN, Eotaxin‐3, MBP‐1) and urine (OPN) biomarkers were increased in EoE compared to control. A panel comprising CLC/GAL‐10, Eotaxin‐3, ECP, EDN, MBP‐1, and AEC was superior to AEC alone in distinguishing EoE from control. AEC, CLC/GAL‐10, ECP, and MBP‐1 were significantly decreased in patients with esophageal eosinophil counts <15/hpf in response to treatment. AEC, CLC/GAL‐10, ECP, EDN, OPN, and MBP‐1 each predicted esophageal eosinophil counts utilizing mixed models controlled for age, gender, treatment, and atopy; AEC combined with MBP‐1 best predicted the counts. Conclusions We identified novel panels of eosinophil‐associated proteins that along with AEC are superior to AEC alone in distinguishing EoE from controls and predicting esophageal eosinophil counts.

Models and Tools for Investigating Eosinophilic Esophagitis at the Bench

“…In addition to peripheral blood eosinophils, there has been great interest in discovering non-invasive biomarkers for EoE in serum. Eotaxin-3, CLC, ECP, EDN, MBP, IL-15, and TGFβ1 have been reported to be elevated in EoE ( 16 , 60 , 64 , 65 ). Ishihara et al.…”

“…In addition to peripheral blood eosinophils, there has been great interest in discovering non-invasive biomarkers for EoE in serum. Eotaxin-3, CLC, ECP, EDN, MBP, IL-15, and TGFb1 have been reported to be elevated in EoE (16,60,64,65). Ishihara et al found that BCA-1, HCC-1, CTACK, SDF-1, MIP3B, and SCCA2 were elevated in EoE patients, but there was large overlap between patients with EoE and other eosinophilic gastrointestinal diseases (66).…”

Galectin-10 as a Potential Biomarker for Eosinophilic Diseases

“…Furuta et al [ 86 ]. and Ackerman et al [ 87 ]. measured galectin-10 concentrations in esophageal luminal samples from patients with eosinophilic esophagitis and found that these concentrations correlated well with eosinophilic inflammation in tissue.…”

Applications of Artificial Intelligence to Eosinophilic Esophagitis

“…Artificial intelligence combined with large datasets has the potential to improve the effectiveness of biomarker panels beyond linear regression. Wechler et al used a random forest model to combine six eosinophil associated proteins in the blood and two urine biomarkers to accurately predict EoE 84% of the time [44]. Their model also found a new biomarker with significant association with positive EoE.…”