Blood levels of long non-coding RNAs may be NMOSD biomarkers

These molecules are known to help regulate gene activity

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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A squirting dropper is shown next to vials of blood.

Certain long non-coding RNAs (lncRNAs) — a family of molecules that can regulate gene activity — tied to immune function were at significantly higher levels in the blood of people with neuromyelitis optica spectrum disorder (NMOSD) compared with the general population, a study reports.

All four evaluated markers — NEAT1, PANDAR, TUG1, and MEG3 — also accurately distinguished NMOSD patients from other adults, with MEG3 having the best diagnostic use.

Researchers believe their work may position these lncRNAs as disease biomarkers for NMOSD.

The study, “Significant up‑regulation of lncRNAs in neuromyelitis optica spectrum disorder,” was published in Scientific Reports.

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Four lncRNAs studied all linked to inflammation or immune function

Long non-coding RNAs are a class of molecules that regulate gene activity to influence protein production. In particular, certain ones affect the growth and activity of immune cells, and have been implicated in autoimmune diseases.

As such, they also could influence the onset and progression of NMOSD, an autoimmune disease caused by self-reactive antibodies that target the otherwise healthy nervous system.

Indeed, a number of studies have observed altered lncRNAs in the blood of NMOSD patients, but their possible role in driving disease processes is not known.

Scientists in Iran measured the activity of the genes encoding four immune-associated lncRNAs in the blood of 42 NMOSD patients, matched by age and sex with 48 people without this disease serving as controls. All were seen at hospitals affiliated with Shahid Beheshti University of Medical Sciences in Tehran.

The ones they chose to measure — NEAT1, PANDAR, TUG1, and MEG3 — each have been linked to inflammation or immune function, and previously implicated in multiple sclerosis (MS), a related autoimmune disease marked, like NMOSD, by damage to nerve cells and the protective myelin coating of their axons.

“Accordingly, deregulation of the chosen lncRNAs might be involved in the NMOSD pathobiology [disease processes] or used as disease markers,” the researchers wrote.

Ten men (mean age 39.9) and 32 women (mean age 37.6) made up the NMOSD group, and all were positive for aquaporin-4 antibodies, the most common type of NMOSD-causing antibody.

Gene activity, reflecting lncRNA levels, was found to be significantly elevated in NMOSD patients compared to controls for all four evaluated lncRNAs. Findings were similar between male and female patients.

Each individual lncRNA was able to accurately differentiate NMOSD from controls, but MEG3 was best, showing 100% sensitivity and specificity. That means that it always positively identified NMOSD patients (sensitivity) and never incorrectly identified a control as having NMOSD (specificity).

MEG3 may distinguish NMOSD from multiple sclerosis, a related disease

Taking into account both sensitivity and specificity, PANDAR had a 97% diagnostic accuracy, NEAT1 was 89% accurate, and TUG1 was 88% accurate.

Moreover, TUG1 and PANDAR expression correlated with age, with a higher expression linked to an older current age and age at NMOSD onset. Lower NEAT1 expression associated with greater disability at disease onset.

“Cumulatively, NEAT1, PANDAR, MEG3 and TUG1 lncRNAs can be considered as appropriate disease markers for NMOSD,” the researchers wrote.

They noted that while NEAT1, PANDAR, and TUG1, have been shown to be elevated in the blood of MS patients, MEG3 is seen to be decreased during active (relapse) phases of MS.

As such, MEG3 might differentiate between the two conditions, whereas “other lncRNAs may just indicate the presence of an autoimmune condition, not differentiating between MS and NMOSD,” the researchers wrote.

In terms of disease mechanisms, the researchers believe the molecules’ increased expression in the blood might contribute to “unbalanced immune responses,” including the overactivation of certain immune cells.

“For better assessment of the role of these lncRNAs in … NMOSD, we suggest assessment of their expression in different sets of blood cells,” the team concluded.