SAN DIEGO—Absence of miR-219, a microRNA (miRNA), in CSF could be a biomarker of multiple sclerosis (MS), according to data presented at the ACTRIMS 2018 Forum. If confirmed, the results could provide an objective measure to improve the diagnosis of MS.
When demyelination occurs in healthy individuals, remyelination follows. In the latter process, oligodendrocyte precursor cells repopulate the demyelinated area and create new myelin. Although large numbers of these cells surround new MS lesions, the precursor cells may fail to differentiate into mature oligodendrocytes, and thus fail to remyelinate the lesions. Data suggest that miR-219 is necessary for oligodendrocyte precursor cell differentiation in mice and rats.
Brigit A. de Jong, MD, PhD, a neurologist at Radboud University Medical Center in Nijmegen, the Netherlands, and colleagues found decreased miR-219 expression in the tissue of patients with MS, compared with healthy controls. To investigate whether CSF levels of miR-219 could be a biomarker of MS, the investigators performed quantitative polymerase chain reaction on samples taken from patients with MS and controls.
An Analysis of Three Cohorts
Dr. de Jong and colleagues analyzed three independent cohorts in their study. Cohort 1 included 24 participants, Cohort 2 included 115 participants, and Cohort 3 included 112 participants. Study participants included healthy controls and patients with clinically isolated syndrome (CIS), relapsing-remitting MS, secondary progressive MS, primary progressive MS, inflammatory neurologic disease, noninflammatory neurologic disease, Alzheimer’s disease, or idiopathic intracranial hypertension. In all, 148 of the participants (59%) were women.
The absence of miR-219 in CSF was consistently associated with MS. In Cohort 1, the odds ratio for a diagnosis of progressive MS was 20.8, compared with controls, if CSF miR-219 was undetectable. In Cohort 2, the odds ratio for a diagnosis of MS or CIS was 2.6, compared with controls, if CSF miR-219 was undetectable. The odds ratio for a diagnosis of progressive MS was 3.6, compared with other neurologic disorders, if CSF miR-219 was undetectable in this cohort. In Cohort 3, the odds ratio for a diagnosis of MS was 39.7, compared with controls, if CSF miR-219 was undetectable.
Advantages of miRNAs
Detecting miRNAs in CSF is difficult because of the low levels at which they are present, said the authors. Nevertheless, miRNAs could be advantageous biomarkers because they are highly stable in body fluids, and the corresponding detection assays can be developed and multiplexed easily. Assessing the performance of miR-219 as a biomarker in situations in which MS cannot be differentiated from MS mimics will require future research, they concluded.
—Erik Greb
Suggested Reading
Agah E, Zardoui A, Saghazadeh A, et al. Osteopontin (OPN) as a CSF and blood biomarker for multiple sclerosis: A systematic review and meta-analysis. PLoS One. 2018 Jan 18;13(1):e0190252.
Bruinsma IB, van Dijk M, Bridel C, et al. Regulator of oligodendrocyte maturation, miR-219, a potential biomarker for MS. J Neuroinflammation. 2017;14(1):235.
Puz P, Steposz A, Lasek-Bal A, et al. Diagnostic methods used in searching for markers of atrophy in patients with multiple sclerosis. Neurol Res. 2018;40(2):110-116.