IL-1RA Biomarker Predicts Disability in Multiple Sclerosis

Stephanie Blandford, MSc, PhD candidate

Data from a recent study suggest that the interleukin-1 receptor antagonist (IL-1RA) biomarker can predict disability in people with multiple sclerosis (MS).¹

Findings from the study were presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2021, February 25-27, 2021, by Stephanie Blandford, MSc, PhD candidate, Neuroimmunology Laboratory, Health Sciences Centre, Memorial University of Newfoundland, and colleagues. “MS is a chronic inflammatory demyelinating and neurodegenerative disorder. IL-1RA is an endogenous soluble antagonist of the IL-1 receptor and blocks the pro-inflammatory effects of IL-1𝛽 that are known to contribute to MS pathology,” Blandford and colleagues wrote.

Blandford and colleagues sought to determine if IL-1RA is associated with disability in MS and how the biomarker correlates with neurofilament light (NfL) levels in cerebrospinal fluid (CSF). They collected peripheral blood and CSF from patients with MS that consented to participate in the study. Both prospective and retrospective chart analysis were used to collect the patients’ demographic and clinical variables, such as past relapse activity.

The researchers measured circulating levels of IL-1RA, IL-18, and IL-1β in plasma. IL-1RA was measured via Bio-plex multiplex immunoassay kits and NfL was measured with an enzyme-linked immunosorbent assay (ELISA). They used primary human macrophages and microglia to investigate IL-1RA in vitro and post-mortem MS tissue samples in situ.

Blandford and colleagues conducted a multiple regression analysis and found that IL-1RA levels in plasma were correlated with expanded disability status scale (EDSS) score independent of other variables such as age, sex, disease-modifying therapy (DMT), or previous relapse activity. In a separate cohort, the researchers also found CSF IL-1RA to be significantly correlated with NfL.

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The researchers found that induction of the NLRP3 inflammasome, a pathological hallmark within MS lesions, led to increased release of IL-1RA from primary human microglia and macrophages in vitro. IL-1RA⁺ macrophages/microglia (CD68⁺) were present at the rim of mixed active/inactive MS lesions in the central nervous system.

“Results presented in this study demonstrate that IL-1RA is a novel exploratory soluble biomarker in MS that is correlated with CSF NfL levels and predicts disability independent of age, sex, disease modifying therapy, and previous relapse activity,” Blandford and colleagues concluded.

Alessandra Musella, PhD, et al previously wrote about the potential of targeting IL-1 in MS in an editorial published in Expert Opinion on Therapeutic Targets. They discuss several studies that support the efficacy of targeting the receptor in MS, but note its interactions in multiple pathways may have unforeseen consequences for treatment.²

“Despite enormous progress that has been made in understanding the contribution of the IL-1 system in MS pathogenesis, the complex interaction between the immune and nervous systems has left open several unexplored roads,” Musella and colleagues wrote.

“Integration of further clinical studies with further precious preclinical research of the IL-1 system will provide an important opportunity not only to monitor or predict the course of MS disease but also to identify selective and compartmentalized IL-1 axis as a therapeutic target.”

For more coverage of ACTRIMS Forum 2021, click here.

REFERENCES

1. Blandford SN, Galloway D, Williams JB, et al. Il-1 receptor antagonist: A novel soluble biomarker that correlates with disabilty and neurofilament light in multiple sclerosis. Presented at ACTRIMS Annual Forum; February 25-27, 2021. Abstract P019.
2. Musella A, Fresegna D, Rizzo FR, et al. ‘Prototypical’ proinflammatory cytokine (IL-1) in multiple sclerosis: role in pathogenesis and therapeutic targeting. Expert Opin. Ther. Targets. 2020; 24: 37-46. doi: 10.1080/14728222.2020.1709823