Kate Johnson

February 25, 2015

HOUSTON — In patients with eosinophilic esophagitis, microRNAs in the saliva might one day be used to diagnose and manage the disease, according to a pilot study.

"The technology we used to measure miRNAs is readily available and already inexpensive," said senior investigator Faoud Ishmael, MD, from Pennsylvania State University College of Medicine in Hershey.

"It's possible that a commercial assay could be available within the next 5 years or so," he told Medscape Medical News.

The pilot study, presented here at the American Academy of Allergy, Asthma & Immunology 2015, is part of the ongoing search for noninvasive biomarkers of eosinophilic esophagitis, especially in children.

"The problem with eosinophilic esophagitis is that the only way to diagnose and monitor response is to perform invasive endoscopies to biopsy the esophagus, which can be difficult and possibly dangerous," said Dr Ishmael.

But miRNAs, which are made by most cells in the body and are secreted into saliva and other body fluids, could serve as a "fingerprint" of the disease, he suggested.

"They are important regulators of inflammation, and their expression is altered in diseases such as eosinophilic esophagitis. About 2000 miRNAs have been discovered in humans so far, but only about 100 to 150 are easily detectable in biofluids, and the pattern of expression of these 100 or so varies across many diseases," he explained.

Detectable in Biofluids

The study involved 15 adults with eosinophilic esophagitis. Each provided saliva samples at the time of diagnostic esophageal biopsy and after 2 months of swallowed fluticasone therapy.

Expression profiles from untreated eosinophilic esophagitis patients were compared with those from healthy control subjects. There was a significant relation between eosinophil count and the expression of miR-3613-3p (P = .005), but not the expression of miR-4668 (P = .06) or miR-570-3p, reported investigator Theodore Kelbel, MD, from the Penn State Hershey Medical Center.

After treatment, there was a significant reduction in the expression of miR-3613-3p and miR-4668 (P < .05) in eosinophilic esophagitis patients, but the expression of miR-570-3p did not change.

The expression of miR-3613-3p and miR-4668, however, did not reach the levels seen in the control group.

"Perhaps this is just a function of patients only being 2 months on therapy. If they'd been on therapy longer, maybe levels would have continued to go down," said Dr Kelbel.

"We are now performing these studies in larger numbers of patients to confirm that our findings are valid and clinically useful," Dr Ishmael reported.

The investigators found that miRNAs might be involved in asthma, and might have similar diagnostic potential in that disease. Dr Ishmael said they are hopeful that, in the future, "these miRNAs could be manipulated for a generation of new anti-inflammatory therapies."

These findings suggest that "noninvasive diagnosis and/or eosinophilic esophagitis status monitoring may be possible in the near future," said Ting Wen, PhD, from Cincinnati Children's Hospital.

However, "whether this noninvasive approach will replace the current conventional method depends on the reproducibility and the to-be-proven specificity of the test," he told Medscape Medical News. "There is still a long way to go."

Dr Wen and his colleagues recently developed the eosinophilic esophagitis diagnostic panel, a molecular test that is currently used on biopsied tissue when the initial esophageal biopsy results are ambiguous.

A reliable noninvasive biomarker for the disease could "save patients the time, cost, and suffering of obtaining at least five esophageal biopsies," he pointed out.

Other approaches currently being developed include blood miRNA, exhaled breath condensate miRNA, and esophageal lavage cytokine levels, Dr Wen reported. "All of these hold strong potential," he said.

Dr Ishmael, Dr Kelbel, and Dr Wen have disclosed no relevant financial relationships.

American Academy of Allergy, Asthma & Immunology (AAAAI) 2015: Abstract 250. Presented February 21, 2015.


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