EULAR 2012: MicroRNAs’ Role in Rheumatic Diseases Coming into Sharper Focus

Hairpin loops from a pre-miRNA.

BERLIN—MicroRNAs (miRNAs) are poised to play a big role in the future understanding and treatment of rheumatoid arthritis (RA), researchers said here at the European League Against Rheumatism (EULAR) 2012 Annual European Congress of Rheumatology, held June 6–9.

New discoveries into the role of several miRNA types are helping to flesh out the miRNA “puzzle” that researchers have been presented with, said Astrid Jungel, PhD, senior post-doc at the University of Zurich in Switzerland and an expert in acetylation.

Arthritis

Recent work on miR155-knockout mice showed that they are resistant to collagen-induced arthritis.^1,2 “These animals showed a suppression of antigen-specific T cells that had no anticollagen antibodies, and they had reduced articular inflammation, leaving us with the question, Is miR155 a possible new target?” Dr. Jungel said.

Other work has shown that miR146a is upregulated in CD4-positive T cells of RA patients.³

Administering double-stranded miR146a prevents joint destruction in collagen-induced arthritis, but it doesn’t seem to lessen inflammation. This suggests that this might be another therapeutic target, Dr. Jungel said.⁴

Still other work has shown that miR203 is upregulated in RA synovial fibroblasts; it is not regulated by inflammatory cytokines or toll-like receptor ligands, but through epigenetic mechanisms.⁵

“The network of microRNAs is turning out to be a novel factor in the pathogenesis of RA and until now we’ve known only a few pieces, and it’s up to us to fill this up,” said Dr. Jungel, referring to the missing puzzle pieces. “It looks like microRNAs certainly will change the biomarkers we have,” allowing for testing of biomarkers noninvasively through sera and synovial fluid. “It will have an impact on the prediction of therapeutic response. It will be used as a new therapeutic target and it will help us understand better the pathogenesis of the disease.”

Sjögren’s

Gabor Illei, MD, PhD, chief of the Sjögren’s Syndrome Clinic at the National Institutes of Health (NIH) in Bethesda, Md., said miRNAs hold great potential value as biomarkers, even though their precise role in rheumatic diseases is still being defined.

“MicroRNAs play an important role in lymphocyte development, control of immunity, control of inflammation, fibrosis—all of which are important for connective tissue diseases,” he said. “Therefore, it is expected that connective tissue diseases will be associated with alterations in microRNA expression. But [whether this] is reflective of the underlying process or this is causative in humans is still unclear.”

He discussed the work of his group at the NIH on the miRNAs 574 and 768-3p in Sjögren’s syndrome.