Interleukin-1 receptor antagonist: An exploratory plasma biomarker that correlates with disability and provides pathophysiological insights in relapsing-remitting multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disorder. Interleukin-1 receptor antagonist (IL-1RA) is an endogenous soluble antagonist of the IL-1 receptor and blocks the pro-inflammatory effects of IL-1ß known to contribute to MS pathology. The objectives of this study were to determine whether IL-1RA is associated with disability in MS and how this correlates with neurofilament light (NfL) levels in cerebrospinal fluid (CSF). METHODS: Peripheral blood and CSF were collected from consenting MS patients. Patient demographic and clinical variables, including past relapse activity, were also collected. Circulating levels of IL-1RA, IL-18, and IL-1ß were measured in plasma; IL-1RA and NfL were measured in the CSF via Bio-plex multiplex immunoassay kits and ELISA, respectively. IL-1RA expression was investigated in vitro using primary human macrophages and microglia, and in situ using post-mortem MS tissue. RESULTS: Following a multiple regression analysis, IL-1RA levels in plasma correlated with expanded disability status scale score independent of all other variables. In a separate cohort, CSF IL-1RA significantly correlated with NfL. In vitro, 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 the CNS, IL-1RA+ macrophages/microglia were present at the rim of mixed active/inactive MS lesions. CONCLUSIONS: Results presented in this study demonstrate that IL-1RA is a novel exploratory biomarker in relapsing-remitting MS, which correlates with disability and provides mechanistic insights into the regulatory inflammatory responses within the demyelinated CNS.

Low Seroprevalence of Lyme Disease Among Multiple Sclerosis Patients in New Brunswick.

The signs and symptoms of Lyme neuroborreliosis can overlap with non-infectious degenerative diseases such as multiple sclerosis (MS). In this study, we assessed a cohort of MS patients in Atlantic Canada for serological evidence of Lyme disease (LD). No positive serology was identified using the recommended two-tiered algorithm.