MicroRNAs dysregulated in axSpA, study shows
Altered levels found to be linked with inflammation
Certain microRNAs, molecules involved in controlling gene activity, were dysregulated in adults with axial spondyloarthritis (axSpA), a study found.
Altered levels of these microRNAs were linked with elevated blood levels of pro-inflammatory signaling proteins implicated in the development and activity of axSpA.
MicroRNAs as biomarkers “could help improve the early detection and treatment of axSpA,” the researchers wrote in the study, “Deciphering miRNA signatures in axial spondyloarthritis: The link between miRNA-1-3p and pro-inflammatory cytokines,” published in Heliyon.
axSpA is a chronic inflammatory disease affecting the spine and sacroiliac joints, where the spinal column meets the pelvis. In radiographic axSpA (r-axSpA), or ankylosing spondylitis (AS), joint damage can be seen on an X-ray, whereas in non-radiographic (nr-axSpA), joint damage isn’t detectable.
Early detection of axSpA is essential to beginning treatment as soon as possible, with the aim of slowing disease progression and maintaining low disease activity. Relevant biomarkers are needed to detect early disease activity and predict progression.
Potential biomarkers
MicroRNAs, or miRNAs, are small segments of RNA that play a role in regulating gene activity and protein production. The levels of these molecules in various bodily fluids have been considered potential biomarkers of various inflammatory diseases, including rheumatoid arthritis.
To determine whether miRNAs may act as suitable axSpA biomarkers, a research team in the Czech Republic isolated RNA from immune cells found in the blood of 167 adults with axSpA. Eighty-five of them were diagnosed with AS and 82 with nr-axSpA. Seventy-two people without inflammatory diseases were added as controls.
Disease activity in patients was measured using C-reactive protein (CRP), a blood-based biomarker of systemic (body-wide) inflammation, and the Ankylosing Spondylitis Disease Activity Score (ASDAS). X-ray assessments of the cervical (neck) and lumbar (lower) spine were performed at the study’s start and after two years.
Most patients were in the early stages of disease and predominantly naïve to biologic disease-modifying antirheumatic drugs, called bDMARDs, with 12.6 % starting such treatment over the two years. AS patients had signs of higher disease activity than nr-axSpA and more frequently tested positive for HLA-B27, a well-established genetic risk factor for AS.
Of the initial 432 miRNAs detected, the level of one miRNA, called miR-1-3p, was significantly higher (upregulated) in axSpA patients than controls. At the same time, two miRNAs, miR-1248 and miR-1246, were markedly lower (downregulated) in axSpA patients.
However, none of the changes in these miRNAs demonstrated significant associations with several clinical assessments, including CRP and ASDAS. Nor were there any detectable differences between r-axSpA and nr-axSpA subtypes.
Patients undergoing treatment with non-steroidal anti-inflammatory drugs (NSAIDs) had reduced levels of miR-1-3p, suggesting “a potential role of miRNAs in modulating the pro-inflammatory pathways implicated in axSpA,” the researchers wrote.
The team did find a significant link between elevated miRNA-1-3p and increased production of interleukin-6 (IL-6), a pro-inflammatory immune signaling protein implicated in the development of AS and associated with disease activity.
In contrast, lower miR-1248 was significantly associated with elevated IL-6. In line with these findings, IL-6 levels in the bloodstream were significantly higher across all axSpA patients compared with controls.
Further analysis identified an association between elevated miR-1-3p and higher blood levels of pro-inflammatory signaling proteins IL-17 and TNF. After adjusting for age and sex, TNF levels showed a significant difference between AS and controls but not between nr-axSpA patients and controls.
A computer-based functional analysis suggested that MiR-1-3p targets the gene that codes for IL-6 and is implicated in signaling pathways associated with IL-17 and TNF.
“This study underscores the dysregulation of miR-1-3p, miR-1246, and miR-1248 in axSpA,” the researchers wrote. “The association between miR-1-3p, IL-17, and TNF suggests a potential role for miR-1-3p in the pathogenesis [development] of axSpA.”
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