RESUMO
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.
Assuntos
Doença de Lyme , Neuroborreliose de Lyme , Esclerose Múltipla , Canadá/epidemiologia , Humanos , Doença de Lyme/complicações , Doença de Lyme/epidemiologia , Esclerose Múltipla/epidemiologia , Novo Brunswick , Estudos SoroepidemiológicosRESUMO
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.