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Figure 4. miR-21 regulates T cell polarization through direct targeting of IL-12p35. IL-12p35 is one subunit of the IL-12 cytokine that
promotes differentiation of naïve T cells towards T helper type 1 cells, instead of T helper type 2. Through post-transcriptional regulation,
miR-21 is able to inhibit IL-12p35, also inhibiting Th1 immunity and shifting T cell polarization and function towards T helper type 2

Figure 5. miR-223 is predicted to bind to the 3’ UTR of the transcript for protease inhibitor, SPINK7, leading to barrier damage and
dysfunction in the esophageal epithelium. SPINK7 is required for normal epithelial cell differentiation and protection of the esophagus
from harsh, food-derived proteases. miRWalk 2.0 predicts that miR-223 can target SPINK7 for degradation. A resulting deficiency of
SPINK7 can lead to increased damage of the esophageal epithelium in EoE

EXTRACELLULAR MIRNAS [PLASMA AND SALIVARY MIRNAS] AS NONINVASIVE
BIOMARKERS
The current standard of care for EoE patients is surveillance by esophagogastroduodenoscopy with biopsy. In
children, recurrent endoscopy can be challenging, traumatic and a substantial financial burden for families
[38]
and adult patients alike. These barriers necessitate a search for non-invasive diagnostics and biomarkers .
Dubbed a liquid biopsy, circulating or plasma miRNAs constitute one potential option for a non-invasive
biomarker to monitor disease progression and responses to therapy. Work by T.X. Lu and colleagues in 2012
identified miR-146a, miR-146b and miR-223 as the most abundant circulating miRNAs in plasma differen-
tially expressed between EoE and healthy individuals. Interestingly, miR-146a and miR-223 levels reverse in
EoE patients who achieved remission with glucocorticoids; whereas, elevated miR-146b plasma levels persist
with remission [32,39] . Not only are these miRNAs stable and detectable in the blood of human subjects, these
findings also provide proof-of-concept for future clinical use of miRNAs as non-invasive biomarkers In Lu’s
study, miR-146a and miR-223 had positive predictive values of 0.82 and 0.77 and negative predictive values
of 0.73 and 0.64, respectively. Taken together, this work demonstrates that a simple blood draw with miRNA
profiling could lead to rapid screening and sensitive detection of disease state and treatment responsiveness
[32]
in EoE patients . Moreover, this work is a promising alternative to recurrent, invasive endoscopies and bi-
opsies that are the current standard of care. The lack of current diagnostic tools to assess inflammation and
manage treatment of EoE patients necessitates further investigation of plasma miRNA biomarkers, specifi-
cally miR-146a and miR-223.

Saliva may be yet another source of biomarkers. Extracellular miRNAs are detectable in the oronasaopha-
ryngeal cavity and can also be obtained non-invasively without endoscopy. Although limited, a few recent
pilot studies hint at the potential to reliably detect different miRNAs signatures in saliva of EoE patients vs.
[40]
controls [40,41] . Kelbel et al. analyzed miRNA expression in saliva samples from 15 adult patients with EoE
and 17 healthy controls. They observed increased in miR-570-3p, miR-3613-5p, miR-4668-5p, and miR-30a-